WorldWideScience

Sample records for gut microbiome adopts

  1. Gut microbiome and bone.

    Science.gov (United States)

    Ibáñez, Lidia; Rouleau, Matthieu; Wakkach, Abdelilah; Blin-Wakkach, Claudine

    2018-04-11

    The gut microbiome is now viewed as a tissue that interacts bidirectionally with the gastrointestinal, immune, endocrine and nervous systems, affecting the cellular responses in numerous organs. Evidence is accumulating of gut microbiome involvement in a growing number of pathophysiological processes, many of which are linked to inflammatory responses. More specifically, data acquired over the last decade point to effects of the gut microbiome on bone mass regulation and on the development of bone diseases (such as osteoporosis) and of inflammatory joint diseases characterized by bone loss. Mice lacking a gut microbiome have bone mass alteration that can be reversed by gut recolonization. Changes in the gut microbiome composition have been reported in mice with estrogen-deficiency osteoporosis and have also been found in a few studies in humans. Probiotic therapy decreases bone loss in estrogen-deficient animals. The effect of the gut microbiome on bone tissue involves complex mechanisms including modulation of CD4 + T cell activation, control of osteoclastogenic cytokine production and modifications in hormone levels. This complexity may contribute to explain the discrepancies observed betwwen some studies whose results vary depending on the age, gender, genetic background and treatment duration. Further elucidation of the mechanisms involved is needed. However, the available data hold promise that gut microbiome manipulation may prove of interest in the management of bone diseases. Copyright © 2018 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

  2. Gut metabolome meets microbiome

    DEFF Research Database (Denmark)

    Lamichhane, Santosh; Sen, Partho; Dickens, Alex M

    2018-01-01

    It is well established that gut microbes and their metabolic products regulate host metabolism. The interactions between the host and its gut microbiota are highly dynamic and complex. In this review we present and discuss the metabolomic strategies to study the gut microbial ecosystem. We...... highlight the metabolic profiling approaches to study faecal samples aimed at deciphering the metabolic product derived from gut microbiota. We also discuss how metabolomics data can be integrated with metagenomics data derived from gut microbiota and how such approaches may lead to better understanding...

  3. Metagenomic Analysis of the Human Gut Microbiome

    DEFF Research Database (Denmark)

    dos Santos, Marcelo Bertalan Quintanilha

    Understanding the link between the human gut microbiome and human health is one of the biggest scientific challenges in our decade. Because 90% of our cells are bacteria, and the microbial genome contains 200 times more genes than the human genome, the study of the human microbiome has...... the potential to impact many areas of our health. This PhD thesis is the first study to generate a large amount of experimental data on the DNA and RNA of the human gut microbiome. This was made possible by our development of a human gut microbiome array capable of profiling any human gut microbiome. Analysis...... of our results changes the way we link the gut microbiome with diseases. Our results indicate that inflammatory diseases will affect the ecological system of the human gut microbiome, reducing its diversity. Classification analysis of healthy and unhealthy individuals demonstrates that unhealthy...

  4. Xenobiotic Metabolism and Gut Microbiomes.

    Directory of Open Access Journals (Sweden)

    Anubhav Das

    Full Text Available Humans are exposed to numerous xenobiotics, a majority of which are in the form of pharmaceuticals. Apart from human enzymes, recent studies have indicated the role of the gut bacterial community (microbiome in metabolizing xenobiotics. However, little is known about the contribution of the plethora of gut microbiome in xenobiotic metabolism. The present study reports the results of analyses on xenobiotic metabolizing enzymes in various human gut microbiomes. A total of 397 available gut metagenomes from individuals of varying age groups from 8 nationalities were analyzed. Based on the diversities and abundances of the xenobiotic metabolizing enzymes, various bacterial taxa were classified into three groups, namely, least versatile, intermediately versatile and highly versatile xenobiotic metabolizers. Most interestingly, specific relationships were observed between the overall drug consumption profile and the abundance and diversity of the xenobiotic metabolizing repertoire in various geographies. The obtained differential abundance patterns of xenobiotic metabolizing enzymes and bacterial genera harboring them, suggest their links to pharmacokinetic variations among individuals. Additional analyses of a few well studied classes of drug modifying enzymes (DMEs also indicate geographic as well as age specific trends.

  5. Emerging Technologies for Gut Microbiome Research

    Science.gov (United States)

    Arnold, Jason W.; Roach, Jeffrey; Azcarate-Peril, M. Andrea

    2016-01-01

    Understanding the importance of the gut microbiome on modulation of host health has become a subject of great interest for researchers across disciplines. As an intrinsically multidisciplinary field, microbiome research has been able to reap the benefits of technological advancements in systems and synthetic biology, biomaterials engineering, and traditional microbiology. Gut microbiome research has been revolutionized by high-throughput sequencing technology, permitting compositional and functional analyses that were previously an unrealistic undertaking. Emerging technologies including engineered organoids derived from human stem cells, high-throughput culturing, and microfluidics assays allowing for the introduction of novel approaches will improve the efficiency and quality of microbiome research. Here, we will discuss emerging technologies and their potential impact on gut microbiome studies. PMID:27426971

  6. The gut microbiome in atherosclerotic cardiovascular disease

    DEFF Research Database (Denmark)

    Jie, Zhuye; Xia, Huihua; Zhong, Shi-Long

    2017-01-01

    The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals...... with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular......), with liver cirrhosis, and rheumatoid arthritis. Our data represent a comprehensive resource for further investigations on the role of the gut microbiome in promoting or preventing ACVD as well as other related diseases.The gut microbiota may play a role in cardiovascular diseases. Here, the authors perform...

  7. The gut microbiome in atherosclerotic cardiovascular disease

    DEFF Research Database (Denmark)

    Jie, Zhuye; Xia, Huihua; Zhong, Shi-Long

    2017-01-01

    The gut microbiota has been linked to cardiovascular diseases. However, the composition and functional capacity of the gut microbiome in relation to cardiovascular diseases have not been systematically examined. Here, we perform a metagenome-wide association study on stools from 218 individuals...... with atherosclerotic cardiovascular disease (ACVD) and 187 healthy controls. The ACVD gut microbiome deviates from the healthy status by increased abundance of Enterobacteriaceae and Streptococcus spp. and, functionally, in the potential for metabolism or transport of several molecules important for cardiovascular...... health. Although drug treatment represents a confounding factor, ACVD status, and not current drug use, is the major distinguishing feature in this cohort. We identify common themes by comparison with gut microbiome data associated with other cardiometabolic diseases (obesity and type 2 diabetes...

  8. Alterations of the Gut Microbiome in Hypertension

    Directory of Open Access Journals (Sweden)

    Qiulong Yan

    2017-08-01

    Full Text Available Introduction: Human gut microbiota is believed to be directly or indirectly involved in cardiovascular diseases and hypertension. However, the identification and functional status of the hypertension-related gut microbe(s have not yet been surveyed in a comprehensive manner.Methods: Here we characterized the gut microbiome in hypertension status by comparing fecal samples of 60 patients with primary hypertension and 60 gender-, age-, and body weight-matched healthy controls based on whole-metagenome shotgun sequencing.Results: Hypertension implicated a remarkable gut dysbiosis with significant reduction in within-sample diversity and shift in microbial composition. Metagenome-wide association study (MGWAS revealed 53,953 microbial genes that differ in distribution between the patients and healthy controls (false discovery rate, 0.05 and can be grouped into 68 clusters representing bacterial species. Opportunistic pathogenic taxa, such as, Klebsiella spp., Streptococcus spp., and Parabacteroides merdae were frequently distributed in hypertensive gut microbiome, whereas the short-chain fatty acid producer, such as, Roseburia spp. and Faecalibacterium prausnitzii, were higher in controls. The number of hypertension-associated species also showed stronger correlation to the severity of disease. Functionally, the hypertensive gut microbiome exhibited higher membrane transport, lipopolysaccharide biosynthesis and steroid degradation, while in controls the metabolism of amino acid, cofactors and vitamins was found to be higher. We further provided the microbial markers for disease discrimination and achieved an area under the receiver operator characteristic curve (AUC of 0.78, demonstrating the potential of gut microbiota in prediction of hypertension.Conclusion: These findings represent specific alterations in microbial diversity, genes, species and functions of the hypertensive gut microbiome. Further studies on the causality relationship between

  9. Gut Microbiome of the Canadian Arctic Inuit

    Science.gov (United States)

    Tromas, Nicolas; Amyot, Marc

    2017-01-01

    ABSTRACT Diet is a major determinant of community composition in the human gut microbiome, and “traditional” diets have been associated with distinct and highly diverse communities, compared to Western diets. However, most traditional diets studied have been those of agrarians and hunter-gatherers consuming fiber-rich diets. In contrast, the Inuit of the Canadian Arctic have been consuming a traditional diet low in carbohydrates and rich in animal fats and protein for thousands of years. We hypothesized that the Inuit diet and lifestyle would be associated with a distinct microbiome. We used deep sequencing of the 16S rRNA gene to compare the gut microbiomes of Montrealers with a Western diet to those of the Inuit consuming a range of traditional and Western diets. At the overall microbial community level, the gut microbiomes of Montrealers and Inuit were indistinguishable and contained similar levels of microbial diversity. However, we observed significant differences in the relative abundances of certain microbial taxa down to the subgenus level using oligotyping. For example, Prevotella spp., which have been previously associated with high-fiber diets, were enriched in Montrealers and among the Inuit consuming a Western diet. The gut microbiomes of Inuit consuming a traditional diet also had significantly less genetic diversity within the Prevotella genus, suggesting that a low-fiber diet might not only select against Prevotella but also reduce its diversity. Other microbes, such as Akkermansia, were associated with geography as well as diet, suggesting limited dispersal to the Arctic. Our report provides a snapshot of the Inuit microbiome as Western-like in overall community structure but distinct in the relative abundances and diversity of certain genera and strains. IMPORTANCE Non-Western populations have been shown to have distinct gut microbial communities shaped by traditional diets. The hitherto-uncharacterized microbiome of the Inuit may help us to

  10. Proton pump inhibitors affect the gut microbiome

    NARCIS (Netherlands)

    Imhann, Floris; Bonder, Marc Jan; Vich Vila, Arnau; Fu, Jingyuan; Mujagic, Zlatan; Vork, Lisa; Feenstra, Ettje T.; Jankipersadsing, Soesma A; Cenit, Maria Carmen; Harmsen, Hermie J M; Dijkstra, Gerard; Franke, Lude; Xavier, Ramnik J; Jonkers, Daisy; Wijmenga, Cisca; Weersma, Rinse K; Zhernakova, Alexandra

    BACKGROUND AND AIMS: Proton pump inhibitors (PPIs) are among the top 10 most widely used drugs in the world. PPI use has been associated with an increased risk of enteric infections, most notably Clostridium difficile. The gut microbiome plays an important role in enteric infections, by resisting or

  11. Advancing gut microbiome research using cultivation

    DEFF Research Database (Denmark)

    Sommer, Morten OA

    2015-01-01

    Culture-independent approaches have driven the field of microbiome research and illuminated intricate relationships between the gut microbiota and human health. However, definitively associating phenotypes to specific strains or elucidating physiological interactions is challenging for metagenomic...... approaches. Recently a number of new approaches to gut microbiota cultivation have emerged through the integration of high-throughput phylogenetic mapping and new simplified cultivation methods. These methodologies are described along with their potential use within microbiome research. Deployment of novel...... cultivation approaches should enable improved studies of xenobiotic tolerance and modification phenotypes and allow a drastic expansion of the gut microbiota reference genome catalogues. Furthermore, the new cultivation methods should facilitate systematic studies of the causal relationship between...

  12. Breaking down the gut microbiome composition in multiple sclerosis.

    Science.gov (United States)

    Budhram, Adrian; Parvathy, Seema; Kremenchutzky, Marcelo; Silverman, Michael

    2017-04-01

    The gut microbiome, which consists of a highly diverse ecologic community of micro-organisms, has increasingly been studied regarding its role in multiple sclerosis (MS) immunopathogenesis. This review critically examines the literature investigating the gut microbiome in MS. A comprehensive search was performed of PubMed databases and ECTRIMS meeting abstracts for literature relating to the gut microbiome in MS. Controlled studies examining the gut microbiome in patients with MS were included for review. Identified studies were predominantly case-control in their design and consistently found differences in the gut microbiome of MS patients compared to controls. We examine plausible mechanistic links between these differences and MS immunopathogenesis, and discuss the therapeutic implications of these findings. Review of the available literature reveals potential immunopathogenic links between the gut microbiome and MS, identifies avenues for therapeutic advancement, and emphasizes the need for further systematic study in this emerging field.

  13. Enterotypes of the human gut microbiome

    DEFF Research Database (Denmark)

    Arumugam, Manimozhiyan; Raes, Jeroen; Pelletier, Eric

    2011-01-01

    Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previou......Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries....... This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species...

  14. Community assembly of the worm gut microbiome

    Science.gov (United States)

    Gore, Jeff

    It has become increasingly clear that human health is strongly influenced by the bacteria that live within the gut, known collectively as the gut microbiome. This complex community varies tremendously between individuals, but understanding the sources that lead to this heterogeneity is challenging. To address this challenge, we are using a bottom-up approach to develop a predictive understanding of how the microbiome assembles and functions within a simple and experimentally tractable gut, the gut of the worm C. elegans. We have found that stochastic community assembly in the C. elegansintestine is sufficient to produce strong inter-worm heterogeneity in community composition. When worms are fed with two neutrally-competing fluorescently labeled bacterial strains, we observe stochastically-driven bimodality in community composition, where approximately half of the worms are dominated by each bacterial strain. A simple model incorporating stochastic colonization suggests that heterogeneity between worms is driven by the low rate at which bacteria successfully establish new intestinal colonies. We can increase this rate experimentally by feeding worms at high bacterial density; in these conditions the bimodality disappears. We have also characterized all pairwise interspecies competitions among a set of eleven bacterial species, illuminating the rules governing interspecies community assembly. These results demonstrate the potential importance of stochastic processes in bacterial community formation and suggest a role for C. elegans as a model system for ecology of host-associated communities.

  15. Nutrition, the Gut and the Microbiome

    DEFF Research Database (Denmark)

    Kjølbæk, Louise

    , but an optimal diet to improve the success of weight loss maintenance has not reached consensus among worldwide expects. During the last decade, it has been observed that the gut microbiota composition is associated with obesity and obesity-associated diseases. However, a deeper understanding of how the host...... the gut and the microbiome in relation to obesity and obesity-associated diseases. The objective was investigated by the conduct of three studies (KIFU, PROKA, MNG). In KIFU, the effect of habitual calcium intake on faecal fat and energy excretions was investigated by an observational study. The 189...... (PUFA) intakes on the gut microbiota composition was investigated by a randomised cross-over study with two 4-week diets periods and a 4-week washout period. Faecal samples and metabolic markers were collected from 30 subjects before and after each diet period. Results showed that habitual dietary...

  16. The Microbiome-Gut-Behavior Axis: Crosstalk Between the Gut Microbiome and Oligodendrocytes Modulates Behavioral Responses.

    Science.gov (United States)

    Ntranos, Achilles; Casaccia, Patrizia

    2018-01-01

    Environmental and dietary stimuli have always been implicated in brain development and behavioral responses. The gut, being the major portal of communication with the external environment, has recently been brought to the forefront of this interaction with the establishment of a gut-brain axis in health and disease. Moreover, recent breakthroughs in germ-free and antibiotic-treated mice have demonstrated the significant impact of the microbiome in modulating behavioral responses in mice and have established a more specific microbiome-gut-behavior axis. One of the mechanisms by which this axis affects social behavior is by regulating myelination at the prefrontal cortex, an important site for complex cognitive behavior planning and decision-making. The prefrontal cortex exhibits late myelination of its axonal projections that could extend into the third decade of life in humans, which make it susceptible to external influences, such as microbial metabolites. Changes in the gut microbiome were shown to alter the composition of the microbial metabolome affecting highly permeable bioactive compounds, such as p-cresol, which could impair oligodendrocyte differentiation. Dysregulated myelination in the prefrontal cortex is then able to affect behavioral responses in mice, shifting them towards social isolation. The reduced social interactions could then limit microbial exchange, which could otherwise pose a threat to the survival of the existing microbial community in the host and, thus, provide an evolutionary advantage to the specific microbial community. In this review, we will analyze the microbiome-gut-behavior axis, describe the interactions between the gut microbiome and oligodendrocytes and highlight their role in the modulation of social behavior.

  17. Gut microbiome and lipid metabolism : from associations to mechanisms

    NARCIS (Netherlands)

    Wang, Zheng; Koonen, Debby; Hofker, Marten; Fu, Jingyuan

    Purpose of review The gut microbiome has now been convincingly linked to human metabolic health but the underlying causality and mechanisms remain poorly understood. This review focuses on the recent progress in establishing the associations between gut microbiome species and lipid metabolism in

  18. Overweight and the feline gut microbiome - a pilot study

    DEFF Research Database (Denmark)

    Kieler, I. N.; Mølbak, Lars; Hansen, L. L.

    2016-01-01

    Compared with lean humans, the gut microbiota is altered in the obese. Whether these changes are due to an obesogenic diet, and whether the microbiota contributes to adiposity is currently discussed. In the cat population, where obesity is also prevalent, gut microbiome changes associated...... microbiome as compared to lean cats....

  19. Metatranscriptomics of the human gut microbiome

    DEFF Research Database (Denmark)

    Sicheritz-Pontén, Thomas

    2011-01-01

    Our ‘other’ genome is the collective genetic information in all of the microorganisms that are living on and within us. Collectively known as the microbiome, these microbial cells outnumber human cells in the body by more than 10 to 1, and the genes carried by these organisms outnumber the genes ...... that there is a division of labor between the bacterial species in the human gut microbiome.......Our ‘other’ genome is the collective genetic information in all of the microorganisms that are living on and within us. Collectively known as the microbiome, these microbial cells outnumber human cells in the body by more than 10 to 1, and the genes carried by these organisms outnumber the genes...... in the human genome by more than 100 to 1. How these organisms contribute to and affect human health is poorly understood, but the emerging field of metagenomics promises a more comprehensive and complete understanding of the human microbiome. In the European-funded Metagenomics of the Human Intestinal Tract...

  20. Gut microbiomes and their metabolites shape human and animal health.

    Science.gov (United States)

    Park, Woojun

    2018-03-01

    The host genetic background, complex surrounding environments, and gut microbiome are very closely linked to human and animal health and disease. Although significant correlations between gut microbiota and human and animal health have been revealed, the specific roles of each gut bacterium in shaping human and animal health and disease remain unclear. However, recent omics-based studies using experimental animals and surveys of gut microbiota from unhealthy humans have provided insights into the relationships among microbial community, their metabolites, and human and animal health. This editorial introduces six review papers that provide new discoveries of disease-associated microbiomes and suggest possible microbiome-based therapeutic approaches to human disease.

  1. Functional variation in the gut microbiome of wild Drosophila populations.

    Science.gov (United States)

    Bost, Alyssa; Martinson, Vincent G; Franzenburg, Soeren; Adair, Karen L; Albasi, Alice; Wells, Martin T; Douglas, Angela E

    2018-05-26

    Most of the evidence that the gut microbiome of animals is functionally variable, with consequences for the health and fitness of the animal host, is based on laboratory studies, often using inbred animals under tightly controlled conditions. It is largely unknown whether these microbiome effects would be evident in outbred animal populations under natural conditions. In this study, we quantified the functional traits of the gut microbiota (metagenome) and host (gut transcriptome) and the taxonomic composition of the gut microorganisms (16S rRNA gene sequence) in natural populations of three mycophagous Drosophila species. Variation in microbiome function and composition was driven principally by the period of sample collection, while host function varied mostly with Drosophila species, indicating that variation in microbiome traits is determined largely by environmental factors, and not host taxonomy. Despite this, significant correlations between microbiome and host functional traits were obtained. In particular, microbiome functions dominated by metabolism were positively associated with host functions relating to gut epithelial turnover. Much of the functional variation in the microbiome could be attributed to variation in abundance of Bacteroidetes, rather than the two other abundant groups, the γ-Proteobacteria or Lactobacillales. We conclude that functional variation in the interactions between animals and their gut microbiome can be detectable in natural populations and, in mycophagous Drosophila, this variation relates primarily to metabolism and homeostasis of the gut epithelium. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Targeting gut microbiome: A novel and potential therapy for autism.

    Science.gov (United States)

    Yang, Yongshou; Tian, Jinhu; Yang, Bo

    2018-02-01

    Autism spectrum disorder (ASD) is a severely neurodevelopmental disorder that impairs a child's ability to communicate and interact with others. Children with neurodevelopmental disorder, including ASD, are regularly affected by gastrointestinal problems and dysbiosis of gut microbiota. On the other hand, humans live in a co-evolutionary association with plenty of microorganisms that resident on the exposed and internal surfaces of our bodies. The microbiome, refers to the collection of microbes and their genetic material, confers a variety of physiologic benefits to the host in many key aspects of life as well as being responsible for some diseases. A large body of preclinical literature indicates that gut microbiome plays an important role in the bidirectional gut-brain axis that communicates between the gut and central nervous system. Moreover, accumulating evidences suggest that the gut microbiome is involved in the pathogenesis of ASD. The present review introduces the increasing evidence suggesting the reciprocal interaction network among microbiome, gut and brain. It also discusses the possible mechanisms by which gut microbiome influences the etiology of ASD via altering gut-brain axis. Most importantly, it highlights the new findings of targeting gut microbiome, including probiotic treatment and fecal microbiota transplant, as novel and potential therapeutics for ASD diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Rapid changes in the gut microbiome during human evolution.

    Science.gov (United States)

    Moeller, Andrew H; Li, Yingying; Mpoudi Ngole, Eitel; Ahuka-Mundeke, Steve; Lonsdorf, Elizabeth V; Pusey, Anne E; Peeters, Martine; Hahn, Beatrice H; Ochman, Howard

    2014-11-18

    Humans are ecosystems containing trillions of microorganisms, but the evolutionary history of this microbiome is obscured by a lack of knowledge about microbiomes of African apes. We sequenced the gut communities of hundreds of chimpanzees, bonobos, and gorillas and developed a phylogenetic approach to reconstruct how present-day human microbiomes have diverged from those of ancestral populations. Compositional change in the microbiome was slow and clock-like during African ape diversification, but human microbiomes have deviated from the ancestral state at an accelerated rate. Relative to the microbiomes of wild apes, human microbiomes have lost ancestral microbial diversity while becoming specialized for animal-based diets. Individual wild apes cultivate more phyla, classes, orders, families, genera, and species of bacteria than do individual humans across a range of societies. These results indicate that humanity has experienced a depletion of the gut flora since diverging from Pan.

  4. Metabolome of human gut microbiome is predictive of host dysbiosis.

    Science.gov (United States)

    Larsen, Peter E; Dai, Yang

    2015-01-01

    Humans live in constant and vital symbiosis with a closely linked bacterial ecosystem called the microbiome, which influences many aspects of human health. When this microbial ecosystem becomes disrupted, the health of the human host can suffer; a condition called dysbiosis. However, the community compositions of human microbiomes also vary dramatically from individual to individual, and over time, making it difficult to uncover the underlying mechanisms linking the microbiome to human health. We propose that a microbiome's interaction with its human host is not necessarily dependent upon the presence or absence of particular bacterial species, but instead is dependent on its community metabolome; an emergent property of the microbiome. Using data from a previously published, longitudinal study of microbiome populations of the human gut, we extrapolated information about microbiome community enzyme profiles and metabolome models. Using machine learning techniques, we demonstrated that the aggregate predicted community enzyme function profiles and modeled metabolomes of a microbiome are more predictive of dysbiosis than either observed microbiome community composition or predicted enzyme function profiles. Specific enzyme functions and metabolites predictive of dysbiosis provide insights into the molecular mechanisms of microbiome-host interactions. The ability to use machine learning to predict dysbiosis from microbiome community interaction data provides a potentially powerful tool for understanding the links between the human microbiome and human health, pointing to potential microbiome-based diagnostics and therapeutic interventions.

  5. Irritable bowel syndrome: A microbiome-gut-brain axis disorder?

    Science.gov (United States)

    Kennedy, Paul J; Cryan, John F; Dinan, Timothy G; Clarke, Gerard

    2014-01-01

    Irritable bowel syndrome (IBS) is an extremely prevalent but poorly understood gastrointestinal disorder. Consequently, there are no clear diagnostic markers to help diagnose the disorder and treatment options are limited to management of the symptoms. The concept of a dysregulated gut-brain axis has been adopted as a suitable model for the disorder. The gut microbiome may play an important role in the onset and exacerbation of symptoms in the disorder and has been extensively studied in this context. Although a causal role cannot yet be inferred from the clinical studies which have attempted to characterise the gut microbiota in IBS, they do confirm alterations in both community stability and diversity. Moreover, it has been reliably demonstrated that manipulation of the microbiota can influence the key symptoms, including abdominal pain and bowel habit, and other prominent features of IBS. A variety of strategies have been taken to study these interactions, including probiotics, antibiotics, faecal transplantations and the use of germ-free animals. There are clear mechanisms through which the microbiota can produce these effects, both humoral and neural. Taken together, these findings firmly establish the microbiota as a critical node in the gut-brain axis and one which is amenable to therapeutic interventions. PMID:25339800

  6. Host Genetics and Gut Microbiome : Challenges and Perspectives

    NARCIS (Netherlands)

    Kurilshikov, Alexander; Wijmenga, Cisca; Fu, Jingyuan; Zhernakova, Alexandra

    The mammalian gut is colonized by trillions of microorganisms collectively called the microbiome. It is increasingly clear that this microbiome has a critical role of in many aspects of health including metabolism and immunity. While environmental factors such as diet and medications have been shown

  7. A psychology of the human brain-gut-microbiome axis.

    Science.gov (United States)

    Allen, Andrew P; Dinan, Timothy G; Clarke, Gerard; Cryan, John F

    2017-04-01

    In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain-gut-microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress-related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain-gut-microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain-gut-microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain-gut-microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain-gut-microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology.

  8. The human gut microbiome, a taxonomic conundrum.

    Science.gov (United States)

    Sankar, Senthil Alias; Lagier, Jean-Christophe; Pontarotti, Pierre; Raoult, Didier; Fournier, Pierre-Edouard

    2015-06-01

    From culture to metagenomics, within only 130 years, our knowledge of the human microbiome has considerably improved. With >1000 microbial species identified to date, the gastro-intestinal microbiota is the most complex of human biotas. It is composed of a majority of Bacteroidetes and Firmicutes and, although exhibiting great inter-individual variations according to age, geographic origin, disease or antibiotic uptake, it is stable over time. Metagenomic studies have suggested associations between specific gut microbiota compositions and a variety of diseases, including irritable bowel syndrome, Crohn's disease, colon cancer, type 2 diabetes and obesity. However, these data remain method-dependent, as no consensus strategy has been defined to decipher the complexity of the gut microbiota. High-throughput culture-independent techniques have highlighted the limitations of culture by showing the importance of uncultured species, whereas modern culture methods have demonstrated that metagenomics underestimates the microbial diversity by ignoring minor populations. In this review, we highlight the progress and challenges that pave the way to a complete understanding of the human gastrointestinal microbiota and its influence on human health. Copyright © 2015 Elsevier GmbH. All rights reserved.

  9. Gut microbiome and its role in cardiovascular diseases.

    Science.gov (United States)

    Ahmadmehrabi, Shadi; Tang, W H Wilson

    2017-11-01

    In recent years, an interest in intestinal microbiota-host interactions has increased due to many findings about the impact of gut bacteria on human health and disease. Dysbiosis, a change in the composition of the gut microbiota, has been associated with much pathology, including cardiovascular diseases (CVD). This article will review normal functions of the gut microbiome, its link to CVD, and potential therapeutic interventions. The recently discovered contribution of gut microbiota-derived molecules in the development of heart disease and its risk factors has significantly increased attention towards the connection between our gut and heart. The gut microbiome is virtually an endocrine organ, arguably the largest, capable of contributing to and reacting to circulating signaling molecules within the host. Gut microbiota-host interactions occur through many pathways, including trimethylamine-N-oxide and short-chain fatty acids. These molecules and others have been linked to much pathology including chronic kidney disease, atherosclerosis, and hypertension. Although our understanding of gut microbiota-host interactions has increased recently; many questions remain about the mechanistic links between the gut microbiome and CVD. With further research, we may one day be able to add gut microbiota profiles as an assessable risk factor for CVD and target therapies towards the gut microbiota.

  10. The influence of a short-term gluten-free diet on the human gut microbiome

    NARCIS (Netherlands)

    Bonder, Marc Jan; Tigchelaar, Ettje F.; Cai, Xianghang; Trynka, Gosia; Cenit, Maria C; Hrdlickova, Barbara; Zhong, Huanzi; Vatanen, Tommi; Gevers, Dirk; Wijmenga, Cisca; Wang, Yang; Zhernakova, Alexandra

    2016-01-01

    Background: A gluten-free diet (GFD) is the most commonly adopted special diet worldwide. It is an effective treatment for coeliac disease and is also often followed by individuals to alleviate gastrointestinal complaints. It is known there is an important link between diet and the gut microbiome,

  11. Human gut microbiome viewed across age and geography

    Science.gov (United States)

    Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, we characterized bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy child...

  12. The emerging relevance of the gut microbiome in cardiometabolic health

    Science.gov (United States)

    Host metabolic pathways and physiological responses are regulated by signals linking the host to the gut microbial community or microbiome. Here, we draw a spotlight on lipid and bile acid metabolism and inflammatory response as they pertain to cardiometabolic dysfunction. Gut microbial dysbiosis al...

  13. Correlating the Gut Microbiome to Health and Disease

    NARCIS (Netherlands)

    Marques, T.M.; Holster, S.; Wall, R.; König, J.; Brummer, R.J.; Vos, de Willem

    2016-01-01

    The gut microbiota is a complex ecosystem consisting of a diverse population of prokaryotes that has a symbiotic relationship with its host; thus it plays a vital role for the host's health. Our understanding of the effect of the gut microbiome in health and disease has grown substantially over

  14. Metabolome of human gut microbiome is predictive of host dysbiosis

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, Peter E.; Dai, Yang

    2015-09-14

    Background: Humans live in constant and vital symbiosis with a closely linked bacterial ecosystem called the microbiome, which influences many aspects of human health. When this microbial ecosystem becomes disrupted, the health of the human host can suffer; a condition called dysbiosis. However, the community compositions of human microbiomes also vary dramatically from individual to individual, and over time, making it difficult to uncover the underlying mechanisms linking the microbiome to human health. We propose that a microbiome’s interaction with its human host is not necessarily dependent upon the presence or absence of particular bacterial species, but instead is dependent on its community metabolome; an emergent property of the microbiome. Results: Using data from a previously published, longitudinal study of microbiome populations of the human gut, we extrapolated information about microbiome community enzyme profiles and metabolome models. Using machine learning techniques, we demonstrated that the aggregate predicted community enzyme function profiles and modeled metabolomes of a microbiome are more predictive of dysbiosis than either observed microbiome community composition or predicted enzyme function profiles. Conclusions: Specific enzyme functions and metabolites predictive of dysbiosis provide insights into the molecular mechanisms of microbiome–host interactions. The ability to use machine learning to predict dysbiosis from microbiome community interaction data provides a potentially powerful tool for understanding the links between the human microbiome and human health, pointing to potential microbiome-based diagnostics and therapeutic interventions.

  15. Anxiety, Depression, and the Microbiome: A Role for Gut Peptides.

    Science.gov (United States)

    Lach, Gilliard; Schellekens, Harriet; Dinan, Timothy G; Cryan, John F

    2018-01-01

    The complex bidirectional communication between the gut and the brain is finely orchestrated by different systems, including the endocrine, immune, autonomic, and enteric nervous systems. Moreover, increasing evidence supports the role of the microbiome and microbiota-derived molecules in regulating such interactions; however, the mechanisms underpinning such effects are only beginning to be resolved. Microbiota-gut peptide interactions are poised to be of great significance in the regulation of gut-brain signaling. Given the emerging role of the gut-brain axis in a variety of brain disorders, such as anxiety and depression, it is important to understand the contribution of bidirectional interactions between peptide hormones released from the gut and intestinal bacteria in the context of this axis. Indeed, the gastrointestinal tract is the largest endocrine organ in mammals, secreting dozens of different signaling molecules, including peptides. Gut peptides in the systemic circulation can bind cognate receptors on immune cells and vagus nerve terminals thereby enabling indirect gut-brain communication. Gut peptide concentrations are not only modulated by enteric microbiota signals, but also vary according to the composition of the intestinal microbiota. In this review, we will discuss the gut microbiota as a regulator of anxiety and depression, and explore the role of gut-derived peptides as signaling molecules in microbiome-gut-brain communication. Here, we summarize the potential interactions of the microbiota with gut hormones and endocrine peptides, including neuropeptide Y, peptide YY, pancreatic polypeptide, cholecystokinin, glucagon-like peptide, corticotropin-releasing factor, oxytocin, and ghrelin in microbiome-to-brain signaling. Together, gut peptides are important regulators of microbiota-gut-brain signaling in health and stress-related psychiatric illnesses.

  16. Insights into the human gut microbiome and cardiovascular diseases

    Directory of Open Access Journals (Sweden)

    Soumalya Sarkar

    2018-01-01

    Full Text Available The microbiome comprises all of the genetic materials within a microbiota. This can also be referred to as the metagenome of the microbiota. Dysbiosis, a change in the composition of the gut microbiota, has been associated with pathology, including cardiovascular diseases (CVDs. The recently discovered contribution of gut microbiota-derived molecules in the development of heart disease and its risk factors has significantly increased attention toward the connection between our gut and heart. The gut microbiome is virtually an endocrine organ, capable of contributing to and reacting to circulating signaling molecules within the host. Gut microbiota-host interactions occur through many pathways, including trimethylamine-N-oxide and short-chain fatty acids. These molecules and others have been linked to chronic kidney disease, atherosclerosis, and hypertension. Dysbiosis has been implicated in CVD as well as many aspects of obesity, hypertension, chronic kidney disease, and diabetes.

  17. Quantitative metagenomics reveals unique gut microbiome biomarkers in ankylosing spondylitis.

    Science.gov (United States)

    Wen, Chengping; Zheng, Zhijun; Shao, Tiejuan; Liu, Lin; Xie, Zhijun; Le Chatelier, Emmanuelle; He, Zhixing; Zhong, Wendi; Fan, Yongsheng; Zhang, Linshuang; Li, Haichang; Wu, Chunyan; Hu, Changfeng; Xu, Qian; Zhou, Jia; Cai, Shunfeng; Wang, Dawei; Huang, Yun; Breban, Maxime; Qin, Nan; Ehrlich, Stanislav Dusko

    2017-07-27

    The assessment and characterization of the gut microbiome has become a focus of research in the area of human autoimmune diseases. Ankylosing spondylitis is an inflammatory autoimmune disease and evidence showed that ankylosing spondylitis may be a microbiome-driven disease. To investigate the relationship between the gut microbiome and ankylosing spondylitis, a quantitative metagenomics study based on deep shotgun sequencing was performed, using gut microbial DNA from 211 Chinese individuals. A total of 23,709 genes and 12 metagenomic species were shown to be differentially abundant between ankylosing spondylitis patients and healthy controls. Patients were characterized by a form of gut microbial dysbiosis that is more prominent than previously reported cases with inflammatory bowel disease. Specifically, the ankylosing spondylitis patients demonstrated increases in the abundance of Prevotella melaninogenica, Prevotella copri, and Prevotella sp. C561 and decreases in Bacteroides spp. It is noteworthy that the Bifidobacterium genus, which is commonly used in probiotics, accumulated in the ankylosing spondylitis patients. Diagnostic algorithms were established using a subset of these gut microbial biomarkers. Alterations of the gut microbiome are associated with development of ankylosing spondylitis. Our data suggest biomarkers identified in this study might participate in the pathogenesis or development process of ankylosing spondylitis, providing new leads for the development of new diagnostic tools and potential treatments.

  18. Characterization of the human gut microbiome during travelers' diarrhea.

    Science.gov (United States)

    Youmans, Bonnie P; Ajami, Nadim J; Jiang, Zhi-Dong; Campbell, Frederick; Wadsworth, W Duncan; Petrosino, Joseph F; DuPont, Herbert L; Highlander, Sarah K

    2015-01-01

    Alterations in the gut microbiota are correlated with ailments such as obesity, inflammatory bowel disease, and diarrhea. Up to 60% of individuals traveling from industrialized to developing countries acquire a form of secretory diarrhea known as travelers' diarrhea (TD), and enterotoxigenic Escherichia coli (ETEC) and norovirus (NoV) are the leading causative pathogens. Presumably, TD alters the gut microbiome, however the effect of TD on gut communities has not been studied. We report the first analysis of bacterial gut populations associated with TD. We examined and compared the gut microbiomes of individuals who developed TD associated with ETEC, NoV, or mixed pathogens, and TD with no pathogen identified, to healthy travelers. We observed a signature dysbiotic gut microbiome profile of high Firmicutes:Bacteroidetes ratios in the travelers who developed diarrhea, regardless of etiologic agent or presence of a pathogen. There was no significant difference in α-diversity among travelers. The bacterial composition of the microbiota of the healthy travelers was similar to the diarrheal groups, however the β-diversity of the healthy travelers was significantly different than any pathogen-associated TD group. Further comparison of the healthy traveler microbiota to those from healthy subjects who were part of the Human Microbiome Project also revealed a significantly higher Firmicutes:Bacteriodetes ratio in the healthy travelers and significantly different β-diversity. Thus, the composition of the gut microbiome in healthy, diarrhea-free travelers has characteristics of a dysbiotic gut, suggesting that these alterations could be associated with factors such as travel.

  19. Regulation of host metabolism and immunity by the gut microbiome

    DEFF Research Database (Denmark)

    Laursen, Janne Marie

    During recent years, central roles of the gut microbiome in metabolic and immunological diseases have been uncovered, and multiple studies have shown that bacterial-derived components shape host physiology and immune responses via direct cellular interactions. The intestinal immune system...... developed a computational framework for identifying bacteria that produce specific endotoxin variants with opposing immunological effects in metagenomic fecal samples. This framework was used to identify the endotoxin variant distribution amongst bacteria in the gut microbiome of Danes and Chinese...... with obesity and type 2 diabetes. We show for the first time that species producing pro-inflammatory endotoxin variants are vastly underrepresented in the gut microbiome compared to species producing non-inflammatory endotoxin and we identify country-specific gram-negative bacterial modules associated...

  20. The human gut microbiome: current knowledge, challenges, and future directions.

    Science.gov (United States)

    Dave, Maneesh; Higgins, Peter D; Middha, Sumit; Rioux, Kevin P

    2012-10-01

    The Human Genome Project was completed a decade ago, leaving a legacy of process, tools, and infrastructure now being turned to the study of the microbes that reside in and on the human body as determinants of health and disease, and has been branded "The Human Microbiome Project." Of the various niches under investigation, the human gut houses the most complex and abundant microbial community and is an arena for important host-microbial interactions that have both local and systemic impact. Initial studies of the human microbiome have been largely descriptive, a testing ground for innovative molecular techniques and new hypotheses. Methods for studying the microbiome have quickly evolved from low-resolution surveys of microbial community structure to high-definition description of composition, function, and ecology. Next-generation sequencing technologies combined with advanced bioinformatics place us at the doorstep of revolutionary insight into the composition, capability, and activity of the human intestinal microbiome. Renewed efforts to cultivate previously "uncultivable" microbes will be important to the overall understanding of gut ecology. There remain numerous methodological challenges to the effective study and understanding of the gut microbiome, largely relating to study design, sample collection, and the number of predictor variables. Strategic collaboration of clinicians, microbiologists, molecular biologists, computational scientists, and bioinformaticians is the ideal paradigm for success in this field. Meaningful interpretation of the gut microbiome requires that host genetic and environmental influences be controlled or accounted for. Understanding the gut microbiome in healthy humans is a foundation for discovering its influence in various important gastrointestinal and nutritional diseases (eg, inflammatory bowel disease, diabetes, and obesity), and for rational translation to human health gains. Copyright © 2012 Mosby, Inc. All rights

  1. Early-life gut microbiome composition and milk allergy resolution.

    Science.gov (United States)

    Bunyavanich, Supinda; Shen, Nan; Grishin, Alexander; Wood, Robert; Burks, Wesley; Dawson, Peter; Jones, Stacie M; Leung, Donald Y M; Sampson, Hugh; Sicherer, Scott; Clemente, Jose C

    2016-10-01

    Gut microbiota may play a role in the natural history of cow's milk allergy. We sought to examine the association between early-life gut microbiota and the resolution of cow's milk allergy. We studied 226 children with milk allergy who were enrolled at infancy in the Consortium of Food Allergy observational study of food allergy. Fecal samples were collected at age 3 to 16 months, and the children were followed longitudinally with clinical evaluation, milk-specific IgE levels, and milk skin prick test performed at enrollment, 6 months, 12 months, and yearly thereafter up until age 8 years. Gut microbiome was profiled by 16s rRNA sequencing and microbiome analyses performed using Quantitative Insights into Microbial Ecology (QIIME), Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt), and Statistical Analysis of Metagenomic Profiles (STAMP). Milk allergy resolved by age 8 years in 128 (56.6%) of the 226 children. Gut microbiome composition at age 3 to 6 months was associated with milk allergy resolution by age 8 years (PERMANOVA P = .047), with enrichment of Clostridia and Firmicutes in the infant gut microbiome of subjects whose milk allergy resolved. Metagenome functional prediction supported decreased fatty acid metabolism in the gut microbiome of subjects whose milk allergy resolved (η 2  = 0.43; ANOVA P = .034). Early infancy is a window during which gut microbiota may shape food allergy outcomes in childhood. Bacterial taxa within Clostridia and Firmicutes could be studied as probiotic candidates for milk allergy therapy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. Early-life gut microbiome composition and milk allergy resolution

    Science.gov (United States)

    Bunyavanich, Supinda; Shen, Nan; Grishin, Alexander; Wood, Robert; Burks, Wesley; Dawson, Peter; Jones, Stacie M.; Leung, Donald; Sampson, Hugh; Sicherer, Scott; Clemente, Jose C.

    2016-01-01

    Background Gut microbiota may play a role in the natural history of cow’s milk allergy Objective To examine the association between early life gut microbiota and the resolution of cow’s milk allergy Methods We studied 226 children with milk allergy who were enrolled at infancy in the Consortium of Food Allergy (CoFAR) observational study of food allergy. Fecal samples were collected at age 3–16 months, and the children were followed longitudinally with clinical evaluation, milk-specific IgE levels, and milk skin prick test performed at enrollment, 6 months, 12 months, and yearly thereafter up until age 8 years. Gut microbiome was profiled by 16s rRNA sequencing and microbiome analyses performed using QIIME (Quantitative Insights into Microbial Ecology), PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), and STAMP (Statistical Analysis of Metagenomic Profiles). Results Milk allergy resolved by age 8 years in 128 (56.6%) of the 226 children. Gut microbiome composition at age 3–6 months was associated with milk allergy resolution by age 8 years (PERMANOVA P = 0.047), with enrichment of Clostridia and Firmicutes in the infant gut microbiome of subjects whose milk allergy resolved. Metagenome functional prediction supported decreased fatty acid metabolism in the gut microbiome of subjects whose milk allergy resolved (η2 = 0.43, ANOVA P = 0.034). Conclusions Early infancy is a window during which gut microbiota may shape food allergy outcomes in childhood. Bacterial taxa within Clostridia and Firmicutes could be studied as probiotic candidates for milk allergy therapy. PMID:27292825

  3. The influence of a short-term gluten-free diet on the human gut microbiome.

    Science.gov (United States)

    Bonder, Marc Jan; Tigchelaar, Ettje F; Cai, Xianghang; Trynka, Gosia; Cenit, Maria C; Hrdlickova, Barbara; Zhong, Huanzi; Vatanen, Tommi; Gevers, Dirk; Wijmenga, Cisca; Wang, Yang; Zhernakova, Alexandra

    2016-04-21

    A gluten-free diet (GFD) is the most commonly adopted special diet worldwide. It is an effective treatment for coeliac disease and is also often followed by individuals to alleviate gastrointestinal complaints. It is known there is an important link between diet and the gut microbiome, but it is largely unknown how a switch to a GFD affects the human gut microbiome. We studied changes in the gut microbiomes of 21 healthy volunteers who followed a GFD for four weeks. We collected nine stool samples from each participant: one at baseline, four during the GFD period, and four when they returned to their habitual diet (HD), making a total of 189 samples. We determined microbiome profiles using 16S rRNA sequencing and then processed the samples for taxonomic and imputed functional composition. Additionally, in all 189 samples, six gut health-related biomarkers were measured. Inter-individual variation in the gut microbiota remained stable during this short-term GFD intervention. A number of taxon-specific differences were seen during the GFD: the most striking shift was seen for the family Veillonellaceae (class Clostridia), which was significantly reduced during the intervention (p = 2.81 × 10(-05)). Seven other taxa also showed significant changes; the majority of them are known to play a role in starch metabolism. We saw stronger differences in pathway activities: 21 predicted pathway activity scores showed significant association to the change in diet. We observed strong relations between the predicted activity of pathways and biomarker measurements. A GFD changes the gut microbiome composition and alters the activity of microbial pathways.

  4. Control of the gut microbiome by fecal microRNA

    Directory of Open Access Journals (Sweden)

    Shirong Liu

    2016-03-01

    Full Text Available Since their discovery in the early 90s, microRNAs (miRNAs, small non-coding RNAs, have mainly been associated with posttranscriptional regulation of gene expression on a cell-autonomous level. Recent evidence has extended this role by adding inter-species communication to the manifold functional range. In our latest study [Liu S, et al., 2016, Cell Host & Microbe], we identified miRNAs in gut lumen and feces of both mice and humans. We found that intestinal epithelial cells (IEC and Hopx+ cells were the two main sources of fecal miRNA. Deficiency of IEC-miRNA resulted in gut dysbiosis and WT fecal miRNA transplantation restored the gut microbiota. We investigated potential mechanisms for this effect and found that miRNAs were able to regulate the gut microbiome. By culturing bacteria with miRNAs, we found that host miRNAs were able to enter bacteria, specifically regulate bacterial gene transcripts and affect bacterial growth. Oral administration of synthetic miRNA mimics affected specific bacteria in the gut. Our findings describe a previously unknown pathway by which the gut microbiome is regulated by the host and raises the possibility that miRNAs may be used therapeutically to manipulate the microbiome for the treatment of disease.

  5. Genetic Characterization of the Gut Microbiome of Hajj Pilgrims

    KAUST Repository

    Beaudoin, Christopher

    2018-05-01

    Hajj, the annual Islamic pilgrimage to Makkah, Saudi Arabia, is a unique mass gathering event that brings more than 2 million individuals from around the world. Several public health considerations, such as the spread of infectious diseases, must be taken into account with this large temporary influx of people. Gastrointestinal diseases, such as diarrhea, are common at Hajj, yet little is known about the etiology. The human gut microbiome, collection of organisms residing within the intestinal tract, has been under intense study recently, since next generation DNA sequencing technologies allow for extensive surveying of genetic material found in complex biological samples, such as those containing many different organisms. Thus, using 16S rRNA and metagenomic shotgun sequencing, we have characterized the gut microbiome of over 612 pilgrims with and without diarrhea. Several metadata factors, such as hospitalization and different comorbidities, were found to have significant effects on the overall gut microbiome composition. Metagenomic shotgun sequencing efforts revealed the presence of antimicrobial resistance genes originating from disparate regions from around the world. This study provides a snapshot of information concerning the health status of the gut microbiome of Hajj pilgrims and provides more context to the investigation of how to best prepare for mass gathering events.

  6. Gut microbiomes of Malawian twin pairs discordant for kwashiorkor

    Science.gov (United States)

    Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin ...

  7. Gut microbiome development along the colorectal adenoma-carcinoma sequence

    DEFF Research Database (Denmark)

    Feng, Qiang; Liang, Suisha; Jia, Huijue

    2015-01-01

    factors indicates that high intake of red meat relative to fruits and vegetables appears to associate with outgrowth of bacteria that might contribute to a more hostile gut environment. These findings suggest that faecal microbiome-based strategies may be useful for early diagnosis and treatment......Colorectal cancer, a commonly diagnosed cancer in the elderly, often develops slowly from benign polyps called adenoma. The gut microbiota is believed to be directly involved in colorectal carcinogenesis. The identity and functional capacity of the adenoma- or carcinoma-related gut microbe...

  8. Richness of human gut microbiome correlates with metabolic markers

    DEFF Research Database (Denmark)

    Le Chatelier, Emmanuelle; Nielsen, Trine; Qin, Junjie

    2013-01-01

    We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus ...... and obese participants. Our classifications based on variation in the gut microbiome identify subsets of individuals in the general white adult population who may be at increased risk of progressing to adiposity-associated co-morbidities....

  9. Recruitment and establishment of the gut microbiome in arctic shorebirds.

    Science.gov (United States)

    Grond, Kirsten; Lanctot, Richard B; Jumpponen, Ari; Sandercock, Brett K

    2017-12-01

    Gut microbiota play a key role in host health. Mammals acquire gut microbiota during birth, but timing of gut microbial recruitment in birds is unknown. We evaluated whether precocial chicks from three species of arctic-breeding shorebirds acquire gut microbiota before or after hatching, and then documented the rate and compositional dynamics of accumulation of gut microbiota. Contrary to earlier reports of microbial recruitment before hatching in chickens, quantitative PCR and Illumina sequence data indicated negligible microbiota in the guts of shorebird embryos before hatching. Analyses of chick feces indicated an exponential increase in bacterial abundance of guts 0-2 days post-hatch, followed by stabilization. Gut communities were characterized by stochastic recruitment and convergence towards a community dominated by Clostridia and Gammaproteobacteria. We conclude that guts of shorebird chicks are likely void of microbiota prior to hatch, but that stable gut microbiome establishes as early as 3 days of age, probably from environmental inocula. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Early-life gut microbiome and egg allergy.

    Science.gov (United States)

    Fazlollahi, M; Chun, Y; Grishin, A; Wood, R A; Burks, A W; Dawson, P; Jones, S M; Leung, D Y M; Sampson, H A; Sicherer, S H; Bunyavanich, S

    2018-07-01

    Gut microbiota may play a role in egg allergy. We sought to examine the association between early-life gut microbiota and egg allergy. We studied 141 children with egg allergy and controls from the multicenter Consortium of Food Allergy Research study. At enrollment (age 3 to 16 months), fecal samples were collected, and clinical evaluation, egg-specific IgE measurement, and egg skin prick test were performed. Gut microbiome was profiled by 16S rRNA sequencing. Analyses for the primary outcome of egg allergy at enrollment, and the secondary outcomes of egg sensitization at enrollment and resolution of egg allergy by age 8 years, were performed using Quantitative Insights into Microbial Ecology, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States, and Statistical Analysis of Metagenomic Profiles. Compared to controls, increased alpha diversity and distinct taxa (PERMANOVA P = 5.0 × 10 -4 ) characterized the early-life gut microbiome of children with egg allergy. Genera from the Lachnospiraceae, Streptococcaceae, and Leuconostocaceae families were differentially abundant in children with egg allergy. Predicted metagenome functional analyses showed differential purine metabolism by the gut microbiota of egg-allergic subjects (Kruskal-Wallis P adj  = 0.021). Greater gut microbiome diversity and genera from Lachnospiraceae and Ruminococcaceae were associated with egg sensitization (PERMANOVA P = 5.0 × 10 -4 ). Among those with egg allergy, there was no association between early-life gut microbiota and egg allergy resolution by age 8 years. The distinct early-life gut microbiota in egg-allergic and egg-sensitized children identified by our study may point to targets for preventive or therapeutic intervention. © 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  11. [Gut microbiome and psyche: paradigm shift in the concept of brain-gut axis].

    Science.gov (United States)

    Konturek, Peter C; Zopf, Yurdagül

    2016-05-25

    The concept of the brain-gut axis describes the communication between the central and enteric nervous system. The exchange of information takes place in both directions. The great advances in molecular medicine in recent years led to the discovery of an enormous number of microorganisms in the intestine (gut microbiome), which greatly affect the function of the brain-gut axis. Overview Numerous studies indicate that the dysfunction of the brain-gut axis could lead to both inflammatory and functional diseases of the gastrointestinal tract. Moreover, it was shown that a faulty composition of the gut microbiota in childhood influences the maturation of the central nervous system and thus may favor the development of mental disorders such as autism, depression, or other. An exact causal relationship between psyche and microbiome must be clarified by further studies in order to find new therapeutic options.

  12. Antibiotic resistance potential of the healthy preterm infant gut microbiome

    Directory of Open Access Journals (Sweden)

    Graham Rose

    2017-01-01

    Full Text Available Background Few studies have investigated the gut microbiome of infants, fewer still preterm infants. In this study we sought to quantify and interrogate the resistome within a cohort of premature infants using shotgun metagenomic sequencing. We describe the gut microbiomes from preterm but healthy infants, characterising the taxonomic diversity identified and frequency of antibiotic resistance genes detected. Results Dominant clinically important species identified within the microbiomes included C. perfringens, K. pneumoniae and members of the Staphylococci and Enterobacter genera. Screening at the gene level we identified an average of 13 antimicrobial resistance genes per preterm infant, ranging across eight different antibiotic classes, including aminoglycosides and fluoroquinolones. Some antibiotic resistance genes were associated with clinically relevant bacteria, including the identification of mecA and high levels of Staphylococci within some infants. We were able to demonstrate that in a third of the infants the S. aureus identified was unrelated using MLST or metagenome assembly, but low abundance prevented such analysis within the remaining samples. Conclusions We found that the healthy preterm infant gut microbiomes in this study harboured a significant diversity of antibiotic resistance genes. This broad picture of resistances and the wider taxonomic diversity identified raises further caution to the use of antibiotics without consideration of the resident microbial communities.

  13. Experimental models of the gut microbiome

    NARCIS (Netherlands)

    Venema, K.; Abbeele, P. van den

    2013-01-01

    The human gut contains a diverse microbiota with large potential to influence health. Given the difficulty to access the main sites of the gut, in vitro models have been developed to dynamically monitor microbial processes at the site of metabolic activity. These models range from simple batch

  14. Brain Gut Microbiome Interactions and Functional Bowel Disorders

    Science.gov (United States)

    Mayer, Emeran A.; Savidge, Tor; Shulman, Robert J.

    2014-01-01

    Alterations in the bidirectional interactions between the gut and the nervous system play an important role in IBS pathophysiology and symptom generation. A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. Characterizations of alterations of gut microbiota in unselected IBS patients, and assessment of changes in subjective symptoms associated with manipulations of the gut microbiota with prebiotics, probiotics and antibiotics support a small, but poorly defined role of dybiosis in overall IBS symptoms. It remains to be determined if the observed abnormalities are a consequence of altered top down signaling from the brain to the gut and microbiota, if they are secondary to a primary perturbation of the microbiota, and if they play a role in the development of altered brain gut interactions early in life. Different mechanisms may play role in subsets of patients. Characterization of gut microbiome alterations in large cohorts of well phenotyped patients as well as evidence correlating gut metabolites with specific abnormalities in the gut brain axis are required to answer these questions. PMID:24583088

  15. Capturing One of the Human Gut Microbiome's Most Wanted

    DEFF Research Database (Denmark)

    Jeraldo, Patricio; Hernandez, Alvaro; Nielsen, Henrik Bjørn

    2016-01-01

    The role of the microbiome in health and disease is attracting great attention, yet we still know little about some of the most prevalent microorganisms inside our bodies. Several years ago, Human Microbiome Project (HMP) researchers generated a list of "most wanted" taxa: bacteria both prevalent...... the environment, and to lack virulence genes. Thus, the evidence is consistent with a secondary degrader that occupies a host-dependent, nutrient scavenging niche within the gut; its ability to produce butyrate, which is thought to play an anti-inflammatory role, makes it intriguing for the study of diseases...

  16. The human gut microbiome of Latin America populations: a landscape to be discovered.

    Science.gov (United States)

    Magne, Fabien; O'Ryan, Miguel L; Vidal, Roberto; Farfan, Mauricio

    2016-10-01

    The gut microbiome is critical for human health, and its alteration is associated with intestinal, autoimmune and metabolic diseases. Numerous studies have focused on prevention or treatment of dysbiotic microbiome to reduce the risk or effect of these diseases. A key issue is to define the microbiome associated with the state of good health. The purpose of this review is to describe factors influencing the gut microbiome with special emphasis on contributions from Latin America. In addition, we will highlight opportunities for future studies on gut microbiome in Latin America. A relevant factor influencing gut microbiome composition is geographical location associated with specific genetic, dietary and lifestyle factors. Geographical specificities suggest that a universal 'healthy microbiome' is unlikely. Several research programs, mostly from Europe and North America, are extensively sequencing gut microbiome of healthy people, whereas data from Latin America remain scarce yet slowly increasing. Few studies have shown difference in the composition of gut microbiome between their local populations with that of other industrialized countries (North American populations). Latin America is composed of countries with a myriad of lifestyles, traditions, genetic backgrounds and socioeconomic conditions, which may determine differences in gut microbiome of individuals from different countries. This represents an opportunity to better understand the relationship between these factors and gut microbiome.

  17. Structure and function of the healthy pre-adolescent pediatric gut microbiome

    Science.gov (United States)

    The gut microbiome influences myriad host functions, including nutrient acquisition, immune modulation, brain development, and behavior. Although human gut microbiota are recognized to change as we age, information regarding the structure and function of the gut microbiome during childhood is limite...

  18. Xenobiotics and the Human Gut Microbiome: Metatranscriptomics Reveal the Active Players

    OpenAIRE

    Ursell, Luke K.; Knight, Rob

    2013-01-01

    The human gut microbiome plays an important role in the metabolism of xenobiotics. In a recent issue of Cell, Maurice et al. identify the active members of the gut microbiome and show how gene expression profiles change within the gut microbial community in response to antibiotics and host-targeted xenobiotics.

  19. Gut Microbiome and Infant Health: Brain-Gut-Microbiota Axis and Host Genetic Factors.

    Science.gov (United States)

    Cong, Xiaomei; Xu, Wanli; Romisher, Rachael; Poveda, Samantha; Forte, Shaina; Starkweather, Angela; Henderson, Wendy A

    2016-09-01

    The development of the neonatal gut microbiome is influenced by multiple factors, such as delivery mode, feeding, medication use, hospital environment, early life stress, and genetics. The dysbiosis of gut microbiota persists during infancy, especially in high-risk preterm infants who experience lengthy stays in the Neonatal intensive care unit (NICU). Infant microbiome evolutionary trajectory is essentially parallel with the host (infant) neurodevelopmental process and growth. The role of the gut microbiome, the brain-gut signaling system, and its interaction with the host genetics have been shown to be related to both short and long term infant health and bio-behavioral development. The investigation of potential dysbiosis patterns in early childhood is still lacking and few studies have addressed this host-microbiome co-developmental process. Further research spanning a variety of fields of study is needed to focus on the mechanisms of brain-gut-microbiota signaling system and the dynamic host-microbial interaction in the regulation of health, stress and development in human newborns.

  20. The gut microbiome in cardio-metabolic health

    DEFF Research Database (Denmark)

    Hansen, Tue Haldor; Gøbel, Rikke J; Hansen, Torben

    2015-01-01

    that the gut microbiota, as an environmental factor influencing the metabolic state of the host, is readily modifiable through a variety of interventions. In this review we provide an overview of the development of the gut microbiome and its compositional and functional changes in relation to cardio......With the prevalence of cardio-metabolic disorders reaching pandemic proportions, the search for modifiable causative factors has intensified. One such potential factor is the vast microbial community inhabiting the human gastrointestinal tract, the gut microbiota. For the past decade evidence has...... accumulated showing the association of distinct changes in gut microbiota composition and function with obesity, type 2 diabetes and cardiovascular disease. Although causality in humans and the pathophysiological mechanisms involved have yet to be decisively established, several studies have demonstrated...

  1. A hundred-year-old insight into the gut microbiome!

    Science.gov (United States)

    Aziz, Ramy Karam

    2009-12-07

    As the National Institutes of Health-funded Human Microbiome Project enters its second phase, and as a major part of this project focuses on the human gut microbiome and its effects on human health, it might help us to travel a century back in time and examine how microbiologists dealt with microbiome-related challenges similar to those of the 21st century using the tools of their time. An article by Arthur I. Kendall, published in The Journal of Biological Chemistry in November 1909 (Some observations on the study of the intestinal bacteria J Biol Chem 1909, 6:499-507), offers a visionary insight into many of today's hot research questions.

  2. A hundred-year-old insight into the gut microbiome!

    Directory of Open Access Journals (Sweden)

    Aziz Ramy

    2009-12-01

    Full Text Available Abstract As the National Institutes of Health-funded Human Microbiome Project enters its second phase, and as a major part of this project focuses on the human gut microbiome and its effects on human health, it might help us to travel a century back in time and examine how microbiologists dealt with microbiome-related challenges similar to those of the 21st century using the tools of their time. An article by Arthur I. Kendall, published in The Journal of Biological Chemistry in November 1909 (Some observations on the study of the intestinal bacteria J Biol Chem 1909, 6:499-507, offers a visionary insight into many of today's hot research questions.

  3. Overweight and the feline gut microbiome - a pilot study.

    Science.gov (United States)

    Kieler, I N; Mølbak, L; Hansen, L L; Hermann-Bank, M L; Bjornvad, C R

    2016-06-01

    Compared with lean humans, the gut microbiota is altered in the obese. Whether these changes are due to an obesogenic diet, and whether the microbiota contributes to adiposity is currently discussed. In the cat population, where obesity is also prevalent, gut microbiome changes associated with obesity have not been studied. Consequently, the aim of this study was to compare the gut microbiota of lean cats, with that of overweight and obese cats. Seventy-seven rescue-shelter cats housed for ≥3 consecutive days were included in the study. Faecal samples were obtained by rectal swab and, when available, by a paired litter box sample. Body condition was assessed using a 9-point scoring system. DNA was extracted, and the 16S rRNA gene was amplified with a high-throughput quantitative real-time PCR chip. Overweight and obese cats had a significantly different gut microbiota compared to lean cats (p gut microbiome as compared to lean cats. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

  4. Genomic variation landscape of the human gut microbiome

    DEFF Research Database (Denmark)

    Schloissnig, Siegfried; Arumugam, Manimozhiyan; Sunagawa, Shinichi

    2013-01-01

    Whereas large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the practical impact of variation is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 faecal...... polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This indicates...

  5. The Human Neonatal Gut Microbiome: A Brief Review

    Directory of Open Access Journals (Sweden)

    Emily C. Gritz

    2015-03-01

    Full Text Available The field of genomics has expanded into subspecialties such as metagenomics over the course of the last decade and a half. The development of massively parallel sequencing capabilities has allowed for increasingly detailed study of the genome of the human microbiome, the microbial super organ that resides symbiotically within the mucosal tissues and integumentary system of the human host. The gut microbiome, and particularly the study of its origins in neonates, have become subtopics of great interest within the field of genomics. This brief review seeks to summarize recent literature regarding the origins and establishment of the neonatal gut microbiome, beginning in utero, and how it is affected by neonatal nutritional status (breastfed versus formula fed and gestational age (term versus preterm. We also explore the role of dysbiosis, a perturbation within the fragile ecosystem of the microbiome, and its role in the origin of select pathologic states, specifically, obesity and necrotizing enterocolitis in preterm infants. We discuss the evidence supporting enteral pre- and probiotic supplementation of commensal organisms such as Bifidobacterium and Lactobacillus in the neonatal period, and their role in the prevention and amelioration of necrotizing enterocolitis in premature infants. Finally, we review directions to consider for further research to promote human health within this field.

  6. The "Gut Feeling": Breaking Down the Role of Gut Microbiome in Multiple Sclerosis.

    Science.gov (United States)

    Freedman, Samantha N; Shahi, Shailesh K; Mangalam, Ashutosh K

    2018-01-01

    Multiple sclerosis (MS) is a chronic neuroinflammatory disease of the central nervous system with unknown etiology. Recently, the gut microbiota has emerged as a potential factor in the development of MS, with a number of studies having shown that patients with MS exhibit gut dysbiosis. The gut microbiota helps the host remain healthy by regulating various functions, including food metabolism, energy homeostasis, maintenance of the intestinal barrier, inhibition of colonization by pathogenic organisms, and shaping of both mucosal and systemic immune responses. Alteration of the gut microbiota, and subsequent changes in its metabolic network that perturb this homeostasis, may lead to intestinal and systemic disorders such as MS. Here we discuss the findings of recent MS microbiome studies and potential mechanisms through which gut microbiota can predispose to, or protect against, MS. These findings highlight the need of an improved understanding of the interactions between the microbiota and host for developing therapies based on gut commensals with which to treat MS.

  7. Gut Microbiome and Obesity: A Plausible Explanation for Obesity.

    Science.gov (United States)

    Sanmiguel, Claudia; Gupta, Arpana; Mayer, Emeran A

    2015-06-01

    Obesity is a multifactorial disorder that results in excessive accumulation of adipose tissue. Although obesity is caused by alterations in the energy consumption/expenditure balance, the factors promoting this disequilibrium are incompletely understood. The rapid development of new technologies and analysis strategies to decode the gut microbiota composition and metabolic pathways has opened a door into the complexity of the guest-host interactions between the gut microbiota and its human host in health and in disease. Pivotal studies have demonstrated that manipulation of the gut microbiota and its metabolic pathways can affect host's adiposity and metabolism. These observations have paved the way for further assessment of the mechanisms underlying these changes. In this review we summarize the current evidence for possible mechanisms underlying gut microbiota induced obesity. The review addresses some well-known effects of the gut microbiota on energy harvesting and changes in metabolic machinery, on metabolic and immune interactions and on possible changes in brain function and behavior. Although there is limited understanding on the symbiotic relationship between us and our gut microbiome, and how disturbances of this relationship affects our health, there is compelling evidence for an important role of the gut microbiota in the development and perpetuation of obesity.

  8. Gut Microbiome and Obesity: A Plausible Explanation for Obesity

    Science.gov (United States)

    Sanmiguel, Claudia; Gupta, Arpana; Mayer, Emeran A.

    2015-01-01

    Obesity is a multifactorial disorder that results in excessive accumulation of adipose tissue. Although obesity is caused by alterations in the energy consumption/expenditure balance, the factors promoting this disequilibrium are incompletely understood. The rapid development of new technologies and analysis strategies to decode the gut microbiota composition and metabolic pathways has opened a door into the complexity of the guest-host interactions between the gut microbiota and its human host in health and in disease. Pivotal studies have demonstrated that manipulation of the gut microbiota and its metabolic pathways can affect host’s adiposity and metabolism. These observations have paved the way for further assessment of the mechanisms underlying these changes. In this review we summarize the current evidence for possible mechanisms underlying gut microbiota induced obesity. The review addresses some well-known effects of the gut microbiota on energy harvesting and changes in metabolic machinery, on metabolic and immune interactions and on possible changes in brain function and behavior. Although there is limited understanding on the symbiotic relationship between us and our gut microbiome, and how disturbances of this relationship affects our health, there is compelling evidence for an important role of the gut microbiota in the development and perpetuation of obesity. PMID:26029487

  9. Intrinsic association between diet and the gut microbiome: current evidence

    Directory of Open Access Journals (Sweden)

    Winglee K

    2015-10-01

    Full Text Available Kathryn Winglee, Anthony A Fodor Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, Charlotte, NC, USA Abstract: The gut microbiome performs many crucial functions for the human host, but the molecular mechanisms by which host, microbe, and diet interact to mediate health and disease are only starting to be revealed. Here, we review the literature on how changes in the diet affect the microbiome. A number of studies have shown that within a geographic region, different diets (such as vegan vs omnivore are associated with differences in a modest number of taxa, but do not reliably produce radical differences within the gut microbial community. In contrast, studies that look across continents consistently find profoundly different microbial communities between Westernized and traditional populations, although it remains unclear to what extent diet or other differences in lifestyle drive these distinct microbial community structures. Furthermore, studies that place subjects on controlled short-term experimental diets have found the resulting alterations to the gut microbial community to generally be small in scope, with changes that do not overcome initial individual differences in microbial community structure. These results emphasize that the human gut microbial community is relatively stable over time. In contrast, short-term changes in diet can cause large changes in metabolite profiles, including metabolites processed by the gut microbial community. These results suggest that commensal gut microbes have a great deal of genetic plasticity and can activate different metabolic pathways independent of changes to microbial community composition. Thus, future studies of how the diet impacts host health via the microbiome may wish to focus on functional assays such as transcriptomics and metabolomics, in addition to 16S rRNA and whole-genome metagenome shotgun analyses of DNA. Taken together, the literature is most

  10. Impacts of the Human Gut Microbiome on Therapeutics.

    Science.gov (United States)

    Vázquez-Baeza, Yoshiki; Callewaert, Chris; Debelius, Justine; Hyde, Embriette; Marotz, Clarisse; Morton, James T; Swafford, Austin; Vrbanac, Alison; Dorrestein, Pieter C; Knight, Rob

    2018-01-06

    The human microbiome contains a vast source of genetic and biochemical variation, and its impacts on therapeutic responses are just beginning to be understood. This expanded understanding is especially important because the human microbiome differs far more among different people than does the human genome, and it is also dramatically easier to change. Here, we describe some of the major factors driving differences in the human microbiome among individuals and populations. We then describe some of the many ways in which gut microbes modify the action of specific chemotherapeutic agents, including nonsteroidal anti-inflammatory drugs and cardiac glycosides, and outline the potential of fecal microbiota transplant as a therapeutic. Intriguingly, microbes also alter how hosts respond to therapeutic agents through various pathways acting at distal sites. Finally, we discuss some of the computational and practical issues surrounding use of the microbiome to stratify individuals for drug response, and we envision a future where the microbiome will be modified to increase everyone's potential to benefit from therapy.

  11. A geographically-diverse collection of 418 human gut microbiome pathway genome databases

    KAUST Repository

    Hahn, Aria S.; Altman, Tomer; Konwar, Kishori M.; Hanson, Niels W.; Kim, Dongjae; Relman, David A.; Dill, David L.; Hallam, Steven J.

    2017-01-01

    the Pathway Tools software, empowering researchers and clinicians interested in visualizing and interpreting metabolic pathways encoded by the human gut microbiome. For the first time, GutCyc provides consistent annotations and metabolic pathway predictions

  12. Diet rapidly and reproducibly alters the human gut microbiome

    Science.gov (United States)

    David, Lawrence A.; Maurice, Corinne F.; Carmody, Rachel N.; Gootenberg, David B.; Button, Julie E.; Wolfe, Benjamin E.; Ling, Alisha V.; Devlin, A. Sloan; Varma, Yug; Fischbach, Michael A.; Biddinger, Sudha B.; Dutton, Rachel J.; Turnbaugh, Peter J.

    2013-01-01

    Long-term diet influences the structure and activity of the trillions of microorganisms residing in the human gut1–5, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here, we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila, and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale, and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals2, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi, and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids, and the outgrowth of microorganisms capable of triggering inflammatory bowel disease6. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles. PMID:24336217

  13. Sex-Specific Effects of Organophosphate Diazinon on the Gut Microbiome and Its Metabolic Functions.

    Science.gov (United States)

    Gao, Bei; Bian, Xiaoming; Mahbub, Ridwan; Lu, Kun

    2017-02-01

    There is growing recognition of the significance of the gut microbiome to human health, and the association between a perturbed gut microbiome with human diseases has been established. Previous studies also show the role of environmental toxicants in perturbing the gut microbiome and its metabolic functions. The wide agricultural use of diazinon, an organophosphate insecticide, has raised serious environmental health concerns since it is a potent neurotoxicant. With studies demonstrating the presence of a microbiome-gut-brain axis, it is possible that gut microbiome perturbation may also contribute to diazinon toxicity. We investigated the impact of diazinon exposure on the gut microbiome composition and its metabolic functions in C57BL/6 mice. We used a combination of 16S rRNA gene sequencing, metagenomics sequencing, and mass spectrometry-based metabolomics profiling in a mouse model to examine the functional impact of diazinon on the gut microbiome. 16S rRNA gene sequencing revealed that diazinon exposure significantly perturbed the gut microbiome, and metagenomic sequencing found that diazinon exposure altered the functional metagenome. Moreover, metabolomics profiling revealed an altered metabolic profile arising from exposure. Of particular significance, these changes were more pronounced for male mice than for female mice. Diazinon exposure perturbed the gut microbiome community structure, functional metagenome, and associated metabolic profiles in a sex-specific manner. These findings may provide novel insights regarding perturbations of the gut microbiome and its functions as a potential new mechanism contributing to diazinon neurotoxicity and, in particular, its sex-selective effects. Citation: Gao B, Bian X, Mahbub R, Lu K. 2017. Sex-specific effects of organophosphate diazinon on the gut microbiome and its metabolic functions. Environ Health Perspect 125:198-206; http://dx.doi.org/10.1289/EHP202.

  14. Gut microbiome development along the colorectal adenoma-carcinoma sequence.

    Science.gov (United States)

    Feng, Qiang; Liang, Suisha; Jia, Huijue; Stadlmayr, Andreas; Tang, Longqing; Lan, Zhou; Zhang, Dongya; Xia, Huihua; Xu, Xiaoying; Jie, Zhuye; Su, Lili; Li, Xiaoping; Li, Xin; Li, Junhua; Xiao, Liang; Huber-Schönauer, Ursula; Niederseer, David; Xu, Xun; Al-Aama, Jumana Yousuf; Yang, Huanming; Wang, Jian; Kristiansen, Karsten; Arumugam, Manimozhiyan; Tilg, Herbert; Datz, Christian; Wang, Jun

    2015-03-11

    Colorectal cancer, a commonly diagnosed cancer in the elderly, often develops slowly from benign polyps called adenoma. The gut microbiota is believed to be directly involved in colorectal carcinogenesis. The identity and functional capacity of the adenoma- or carcinoma-related gut microbe(s), however, have not been surveyed in a comprehensive manner. Here we perform a metagenome-wide association study (MGWAS) on stools from advanced adenoma and carcinoma patients and from healthy subjects, revealing microbial genes, strains and functions enriched in each group. An analysis of potential risk factors indicates that high intake of red meat relative to fruits and vegetables appears to associate with outgrowth of bacteria that might contribute to a more hostile gut environment. These findings suggest that faecal microbiome-based strategies may be useful for early diagnosis and treatment of colorectal adenoma or carcinoma.

  15. Quantitative microbiome profiling links gut community variation to microbial load.

    Science.gov (United States)

    Vandeputte, Doris; Kathagen, Gunter; D'hoe, Kevin; Vieira-Silva, Sara; Valles-Colomer, Mireia; Sabino, João; Wang, Jun; Tito, Raul Y; De Commer, Lindsey; Darzi, Youssef; Vermeire, Séverine; Falony, Gwen; Raes, Jeroen

    2017-11-23

    Current sequencing-based analyses of faecal microbiota quantify microbial taxa and metabolic pathways as fractions of the sample sequence library generated by each analysis. Although these relative approaches permit detection of disease-associated microbiome variation, they are limited in their ability to reveal the interplay between microbiota and host health. Comparative analyses of relative microbiome data cannot provide information about the extent or directionality of changes in taxa abundance or metabolic potential. If microbial load varies substantially between samples, relative profiling will hamper attempts to link microbiome features to quantitative data such as physiological parameters or metabolite concentrations. Saliently, relative approaches ignore the possibility that altered overall microbiota abundance itself could be a key identifier of a disease-associated ecosystem configuration. To enable genuine characterization of host-microbiota interactions, microbiome research must exchange ratios for counts. Here we build a workflow for the quantitative microbiome profiling of faecal material, through parallelization of amplicon sequencing and flow cytometric enumeration of microbial cells. We observe up to tenfold differences in the microbial loads of healthy individuals and relate this variation to enterotype differentiation. We show how microbial abundances underpin both microbiota variation between individuals and covariation with host phenotype. Quantitative profiling bypasses compositionality effects in the reconstruction of gut microbiota interaction networks and reveals that the taxonomic trade-off between Bacteroides and Prevotella is an artefact of relative microbiome analyses. Finally, we identify microbial load as a key driver of observed microbiota alterations in a cohort of patients with Crohn's disease, here associated with a low-cell-count Bacteroides enterotype (as defined through relative profiling).

  16. The gut mycobiome of the Human Microbiome Project healthy cohort.

    Science.gov (United States)

    Nash, Andrea K; Auchtung, Thomas A; Wong, Matthew C; Smith, Daniel P; Gesell, Jonathan R; Ross, Matthew C; Stewart, Christopher J; Metcalf, Ginger A; Muzny, Donna M; Gibbs, Richard A; Ajami, Nadim J; Petrosino, Joseph F

    2017-11-25

    Most studies describing the human gut microbiome in healthy and diseased states have emphasized the bacterial component, but the fungal microbiome (i.e., the mycobiome) is beginning to gain recognition as a fundamental part of our microbiome. To date, human gut mycobiome studies have primarily been disease centric or in small cohorts of healthy individuals. To contribute to existing knowledge of the human mycobiome, we investigated the gut mycobiome of the Human Microbiome Project (HMP) cohort by sequencing the Internal Transcribed Spacer 2 (ITS2) region as well as the 18S rRNA gene. Three hundred seventeen HMP stool samples were analyzed by ITS2 sequencing. Fecal fungal diversity was significantly lower in comparison to bacterial diversity. Yeast dominated the samples, comprising eight of the top 15 most abundant genera. Specifically, fungal communities were characterized by a high prevalence of Saccharomyces, Malassezia, and Candida, with S. cerevisiae, M. restricta, and C. albicans operational taxonomic units (OTUs) present in 96.8, 88.3, and 80.8% of samples, respectively. There was a high degree of inter- and intra-volunteer variability in fungal communities. However, S. cerevisiae, M. restricta, and C. albicans OTUs were found in 92.2, 78.3, and 63.6% of volunteers, respectively, in all samples donated over an approximately 1-year period. Metagenomic and 18S rRNA gene sequencing data agreed with ITS2 results; however, ITS2 sequencing provided greater resolution of the relatively low abundance mycobiome constituents. Compared to bacterial communities, the human gut mycobiome is low in diversity and dominated by yeast including Saccharomyces, Malassezia, and Candida. Both inter- and intra-volunteer variability in the HMP cohort were high, revealing that unlike bacterial communities, an individual's mycobiome is no more similar to itself over time than to another person's. Nonetheless, several fungal species persisted across a majority of samples, evidence that

  17. Circadian Disruption Changes Gut Microbiome Taxa and Functional Gene Composition.

    Science.gov (United States)

    Deaver, Jessica A; Eum, Sung Y; Toborek, Michal

    2018-01-01

    Disrupted circadian rhythms and alterations of the gut microbiome composition were proposed to affect host health. Therefore, the aim of this research was to identify whether these events are connected and if circadian rhythm disruption by abnormal light-dark (LD) cycles affects microbial community gene expression and host vulnerability to intestinal dysfunction. Mice were subjected to either a 4-week period of constant 24-h light or of normal 12-h LD cycles. Stool samples were collected at the beginning and after the circadian rhythm disruption. A metatranscriptomic analysis revealed an increase in Ruminococcus torques , a bacterial species known to decrease gut barrier integrity, and a decrease in Lactobacillus johnsonii , a bacterium that helps maintain the intestinal epithelial cell layer, after circadian rhythm disruption. In addition, genes involved in pathways promoting host beneficial immune responses were downregulated, while genes involved in the synthesis and transportation of the endotoxin lipopolysaccharide were upregulated in mice with disrupted circadian cycles. Importantly, these mice were also more prone to dysfunction of the intestinal barrier. These results further elucidate the impact of light-cycle disruption on the gut microbiome and its connection with increased incidence of disease in response to circadian rhythm disturbances.

  18. Connections between the human gut microbiome and gestational diabetes mellitus.

    Science.gov (United States)

    Kuang, Ya-Shu; Lu, Jin-Hua; Li, Sheng-Hui; Li, Jun-Hua; Yuan, Ming-Yang; He, Jian-Rong; Chen, Nian-Nian; Xiao, Wan-Qing; Shen, Song-Ying; Qiu, Lan; Wu, Ying-Fang; Hu, Cui-Yue; Wu, Yan-Yan; Li, Wei-Dong; Chen, Qiao-Zhu; Deng, Hong-Wen; Papasian, Christopher J; Xia, Hui-Min; Qiu, Xiu

    2017-08-01

    The human gut microbiome can modulate metabolic health and affect insulin resistance, and it may play an important role in the etiology of gestational diabetes mellitus (GDM). Here, we compared the gut microbial composition of 43 GDM patients and 81 healthy pregnant women via whole-metagenome shotgun sequencing of their fecal samples, collected at 21-29 weeks, to explore associations between GDM and the composition of microbial taxonomic units and functional genes. A metagenome-wide association study identified 154 837 genes, which clustered into 129 metagenome linkage groups (MLGs) for species description, with significant relative abundance differences between the 2 cohorts. Parabacteroides distasonis, Klebsiella variicola, etc., were enriched in GDM patients, whereas Methanobrevibacter smithii, Alistipes spp., Bifidobacterium spp., and Eubacterium spp. were enriched in controls. The ratios of the gross abundances of GDM-enriched MLGs to control-enriched MLGs were positively correlated with blood glucose levels. A random forest model shows that fecal MLGs have excellent discriminatory power to predict GDM status. Our study discovered novel relationships between the gut microbiome and GDM status and suggests that changes in microbial composition may potentially be used to identify individuals at risk for GDM. © The Author 2017. Published by Oxford University Press.

  19. Factors influencing the grass carp gut microbiome and its effect on metabolism.

    Science.gov (United States)

    Ni, Jiajia; Yan, Qingyun; Yu, Yuhe; Zhang, Tanglin

    2014-03-01

    Gut microbiota have attracted extensive attention recently because of their important role in host metabolism, immunity and health maintenance. The present study focused on factors affecting the gut microbiome of grass carp (Ctenopharyngodon idella) and further explored the potential effect of the gut microbiome on metabolism. Totally, 43.39 Gb of screened metagenomic sequences obtained from 24 gut samples were fully analysed. We detected 1228 phylotypes (116 Archaea and 1112 Bacteria), most of which belonged to the phyla Firmicutes, Proteobacteria and Fusobacteria. Totally, 41335 of the detected open reading frames (ORFs) were matched to Kyoto Encyclopedia of Genes and Genomes pathways, and carbohydrate and amino acid metabolism was the main matched pathway deduced from the annotated ORFs. Redundancy analysis based on the phylogenetic composition and gene composition of the gut microbiome indicated that gut fullness and feeding (i.e. ryegrass vs. commercial feed, and pond-cultured vs. wild) were significantly related to the gut microbiome. Moreover, many biosynthesis and metabolism pathways of carbohydrates, amino acids and lipids were significantly enhanced by the gut microbiome in ryegrass-fed grass carp. These findings suggest that the metabolic role played by the gut microbiome in grass carp can be affected by feeding. These findings contribute to the field of fish gut microbial ecology and also provide a basis for follow-up functional studies. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  20. Early Life Experience and Gut Microbiome: The Brain-Gut-Microbiota Signaling System.

    Science.gov (United States)

    Cong, Xiaomei; Henderson, Wendy A; Graf, Joerg; McGrath, Jacqueline M

    2015-10-01

    Over the past decades, advances in neonatal care have led to substantial increases in survival among preterm infants. With these gains, recent concerns have focused on increases in neurodevelopment morbidity related to the interplay between stressful early life experiences and the immature neuroimmune systems. This interplay between these complex mechanisms is often described as the brain-gut signaling system. The role of the gut microbiome and the brain-gut signaling system have been found to be remarkably related to both short- and long-term stress and health. Recent evidence supports that microbial species, ligands, and/or products within the developing intestine play a key role in early programming of the central nervous system and regulation of the intestinal innate immunity. The purpose of this state-of-the-science review is to explore the supporting evidence demonstrating the importance of the brain-gut-microbiota axis in regulation of early life experience. We also discuss the role of gut microbiome in modulating stress and pain responses in high-risk infants. A conceptual framework has been developed to illustrate the regulation mechanisms involved in early life experience. The science in this area is just beginning to be uncovered; having a fundamental understanding of these relationships will be important as new discoveries continue to change our thinking, leading potentially to changes in practice and targeted interventions.

  1. Maturation of the gut microbiome and risk of asthma in childhood

    DEFF Research Database (Denmark)

    Stokholm, Jakob; Blaser, Martin J.; Thorsen, Jonathan

    2018-01-01

    The composition of the human gut microbiome matures within the first years of life. It has been hypothesized that microbial compositions in this period can cause immune dysregulations and potentially cause asthma. Here we show, by associating gut microbial composition from 16S rRNA gene amplicon...... microbial stimulation during the first year of life can trigger their inherited asthma risk. Conversely, adequate maturation of the gut microbiome in this period may protect these pre-disposed children....

  2. Saccharide breakdown and fermentation by the honey bee gut microbiome.

    Science.gov (United States)

    Lee, Fredrick J; Rusch, Douglas B; Stewart, Frank J; Mattila, Heather R; Newton, Irene L G

    2015-03-01

    The honey bee, the world's most important agricultural pollinator, relies exclusively on plant-derived foods for nutrition. Nectar and pollen collected by honey bees are processed and matured within the nest through the activities of honey bee-derived microbes and enzymes. In order to better understand the contribution of the microbial community to food processing in the honey bee, we generated a metatranscriptome of the honey bee gut microbiome. The function of the microbial community in the honey bee, as revealed by metatranscriptome sequencing, resembles that of other animal guts and food-processing environments. We identified three major bacterial classes that are active in the gut (γ-Proteobacteria, Bacilli and Actinobacteria), all of which are predicted to participate in the breakdown of complex macromolecules (e.g. polysaccharides and polypeptides), the fermentation of component parts of these macromolecules, and the generation of various fermentation products, such as short-chain fatty acids and alcohol. The ability of the microbial community to metabolize these carbon-rich food sources was confirmed through the use of community-level physiological profiling. Collectively, these findings suggest that the gut microflora of the honey bee harbours bacterial members with unique roles, which ultimately can contribute to the processing of plant-derived food for colonies. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

  3. Market Integration Predicts Human Gut Microbiome Attributes across a Gradient of Economic Development.

    Science.gov (United States)

    Stagaman, Keaton; Cepon-Robins, Tara J; Liebert, Melissa A; Gildner, Theresa E; Urlacher, Samuel S; Madimenos, Felicia C; Guillemin, Karen; Snodgrass, J Josh; Sugiyama, Lawrence S; Bohannan, Brendan J M

    2018-01-01

    Economic development is marked by dramatic increases in the incidence of microbiome-associated diseases, such as autoimmune diseases and metabolic syndromes, but the lifestyle changes that drive alterations in the human microbiome are not known. We measured market integration as a proxy for economically related lifestyle attributes, such as ownership of specific market goods that index degree of market integration and components of traditional and nontraditional (more modern) house structure and infrastructure, and profiled the fecal microbiomes of 213 participants from a contiguous, indigenous Ecuadorian population. Despite relatively modest differences in lifestyle across the population, greater economic development correlated with significantly lower within-host diversity, higher between-host dissimilarity, and a decrease in the relative abundance of the bacterium Prevotella . These microbiome shifts were most strongly associated with more modern housing, followed by reduced ownership of traditional subsistence lifestyle-associated items. IMPORTANCE Previous research has reported differences in the gut microbiome between populations residing in wealthy versus poorer countries, leading to the assertion that lifestyle changes associated with economic development promote changes in the gut microbiome that promote the proliferation of microbiome-associated diseases. However, a direct relationship between economic development and the gut microbiome has not previously been shown. We surveyed the gut microbiomes of a single indigenous population undergoing economic development and found significant associations between features of the gut microbiome and lifestyle changes associated with economic development. These findings suggest that even the earliest stages of economic development can drive changes in the gut microbiome, which may provide a warning sign for the development of microbiome-associated diseases.

  4. Structure, and culture of the gut microbiome of the Mormon cricket Anabrus simplex

    Science.gov (United States)

    The gut microbiome of insects plays an important role in their ecology and evolution, participating in nutrient acquisition, immunity, and behavior. Microbial community structure within the gut is heavily influenced by differences among gut regions in morphology and physiology, which determine the n...

  5. Rapidly expanding knowledge on the role of the gut microbiome in health and disease

    NARCIS (Netherlands)

    Cenit, M. C.; Matzaraki, V.; Tigchelaar-Feenstra, E. F.; Zhernakova, A.

    2014-01-01

    The human gut is colonized by a wide diversity of micro-organisms, which are now known to play a key role in the human host by regulating metabolic functions and immune homeostasis. Many studies have indicated that the genomes of our gut microbiota, known as the gut microbiome or our "other genome"

  6. An integrated catalog of reference genes in the human gut microbiome

    DEFF Research Database (Denmark)

    Li, Junhua; Jia, Huijue; Cai, Xianghang

    2014-01-01

    Many analyses of the human gut microbiome depend on a catalog of reference genes. Existing catalogs for the human gut microbiome are based on samples from single cohorts or on reference genomes or protein sequences, which limits coverage of global microbiome diversity. Here we combined 249 newly...... signatures. This expanded catalog should facilitate quantitative characterization of metagenomic, metatranscriptomic and metaproteomic data from the gut microbiome to understand its variation across populations in human health and disease.......) comprising 9,879,896 genes. The catalog includes close-to-complete sets of genes for most gut microbes, which are also of considerably higher quality than in previous catalogs. Analyses of a group of samples from Chinese and Danish individuals using the catalog revealed country-specific gut microbial...

  7. Shotgun metagenomics of 250 adult twins reveals genetic and environmental impacts on the gut microbiome

    DEFF Research Database (Denmark)

    Xie, Hailiang; Guo, Ruijin; Zhong, Huanzi

    2016-01-01

    The gut microbiota has been typically viewed as an environmental factor for human health. Twins are well suited for investigating the concordance of their gut microbiomes and decomposing genetic and environmental influences. However, existing twin studies utilizing metagenomic shotgun sequencing...... have included only a few samples. Here, we sequenced fecal samples from 250 adult twins in the TwinsUK registry and constructed a comprehensive gut microbial reference gene catalog. We demonstrate heritability of many microbial taxa and functional modules in the gut microbiome, including those...... associated with diseases. Moreover, we identified 8 million SNPs in the gut microbiome and observe a high similarity in microbiome SNPs between twins that slowly decreases after decades of living apart. The results shed new light on the genetic and environmental influences on the composition and function...

  8. Development of the preterm gut microbiome in twins at risk of necrotising enterocolitis and sepsis.

    Directory of Open Access Journals (Sweden)

    Christopher J Stewart

    Full Text Available The preterm gut microbiome is a complex dynamic community influenced by genetic and environmental factors and is implicated in the pathogenesis of necrotising enterocolitis (NEC and sepsis. We aimed to explore the longitudinal development of the gut microbiome in preterm twins to determine how shared environmental and genetic factors may influence temporal changes and compared this to the expressed breast milk (EBM microbiome. Stool samples (n = 173 from 27 infants (12 twin pairs and 1 triplet set and EBM (n = 18 from 4 mothers were collected longitudinally. All samples underwent PCR-DGGE (denaturing gradient gel electrophoresis analysis and a selected subset underwent 454 pyrosequencing. Stool and EBM shared a core microbiome dominated by Enterobacteriaceae, Enterococcaceae, and Staphylococcaceae. The gut microbiome showed greater similarity between siblings compared to unrelated individuals. Pyrosequencing revealed a reduction in diversity and increasing dominance of Escherichia sp. preceding NEC that was not observed in the healthy twin. Antibiotic treatment had a substantial effect on the gut microbiome, reducing Escherichia sp. and increasing other Enterobacteriaceae. This study demonstrates related preterm twins share similar gut microbiome development, even within the complex environment of neonatal intensive care. This is likely a result of shared genetic and immunomodulatory factors as well as exposure to the same maternal microbiome during birth, skin contact and exposure to EBM. Environmental factors including antibiotic exposure and feeding are additional significant determinants of community structure, regardless of host genetics.

  9. Development of the preterm gut microbiome in twins at risk of necrotising enterocolitis and sepsis.

    Science.gov (United States)

    Stewart, Christopher J; Marrs, Emma C L; Nelson, Andrew; Lanyon, Clare; Perry, John D; Embleton, Nicholas D; Cummings, Stephen P; Berrington, Janet E

    2013-01-01

    The preterm gut microbiome is a complex dynamic community influenced by genetic and environmental factors and is implicated in the pathogenesis of necrotising enterocolitis (NEC) and sepsis. We aimed to explore the longitudinal development of the gut microbiome in preterm twins to determine how shared environmental and genetic factors may influence temporal changes and compared this to the expressed breast milk (EBM) microbiome. Stool samples (n = 173) from 27 infants (12 twin pairs and 1 triplet set) and EBM (n = 18) from 4 mothers were collected longitudinally. All samples underwent PCR-DGGE (denaturing gradient gel electrophoresis) analysis and a selected subset underwent 454 pyrosequencing. Stool and EBM shared a core microbiome dominated by Enterobacteriaceae, Enterococcaceae, and Staphylococcaceae. The gut microbiome showed greater similarity between siblings compared to unrelated individuals. Pyrosequencing revealed a reduction in diversity and increasing dominance of Escherichia sp. preceding NEC that was not observed in the healthy twin. Antibiotic treatment had a substantial effect on the gut microbiome, reducing Escherichia sp. and increasing other Enterobacteriaceae. This study demonstrates related preterm twins share similar gut microbiome development, even within the complex environment of neonatal intensive care. This is likely a result of shared genetic and immunomodulatory factors as well as exposure to the same maternal microbiome during birth, skin contact and exposure to EBM. Environmental factors including antibiotic exposure and feeding are additional significant determinants of community structure, regardless of host genetics.

  10. The microbiome-gut-brain axis: implications for schizophrenia and antipsychotic induced weight gain.

    Science.gov (United States)

    Kanji, S; Fonseka, T M; Marshe, V S; Sriretnakumar, V; Hahn, M K; Müller, D J

    2018-02-01

    With the emergence of knowledge implicating the human gut microbiome in the development and regulation of several physiological systems, evidence has accumulated to suggest a role for the gut microbiome in psychiatric conditions and drug response. A complex relationship between the enteric nervous system, the gut microbiota and the central nervous system has been described which allows for the microbiota to influence and respond to a variety of behaviors and psychiatric conditions. Additionally, the use of pharmaceuticals may interact with and alter the microbiota to potentially contribute to adverse effects of the drug. The gut microbiota has been described in several psychiatric disorders including depression and anxiety, but only a few reports have discussed the role of the microbiome in schizophrenia. The following review examines the evidence surrounding the gut microbiota in behavior and psychiatric illness, the role of the microbiota in schizophrenia and the potential for antipsychotics to alter the gut microbiota and promote adverse metabolic events.

  11. The gut microbiome, symptoms, and targeted interventions in children with cancer: a systematic review.

    Science.gov (United States)

    Bai, Jinbing; Behera, Madhusmita; Bruner, Deborah Watkins

    2018-02-01

    The gut microbiome plays a critical role in maintaining children's health and in preventing and treating children's disease. Current application of the gut microbiome in childhood cancer is still lacking. This study aimed to systematically review the following: (1) alternations in the gut microbiome throughout cancer treatment trajectories in children, (2) the associations between the gut microbiome and gastrointestinal (GI) symptoms and psychoneurological symptoms (PNS), and (3) the efficacy of therapeutic interventions in the gut microbiome in children with cancer. PubMed, EMBASE, the Cochrane Library, and the American Society of Clinical Oncology abstract were searched. Eligible studies included all study types in which the gut microbiome was primarily reported in children with cancer. The Mixed Methods Assessment Tool was used to evaluate the methodology quality of included studies. Seven studies met our eligibility criteria, including two cohort studies, two case-control studies, and three randomized controlled trails. The findings showed that the diversity estimates of the gut microbiome in children with cancer were lower than those of healthy controls both pre- and post-treatment. Children with cancer showed a significantly lower relative abundance of healthy gut microbiome (e.g., Clostridium XIVa and Bifidobacterium) during and after cancer treatment. No adequate literature was identified to support the associations between dysbiosis of the gut microbiome and GI symptoms/PNS. The use of prebiotics (fructooligosaccharides) and probiotics (Bifidobacterium or Lactobacilli) appears to improve the microenvironment of the gut around 1 month (4-5 weeks) during chemotherapy rather than at the beginning of treatment. Data also suggest that both prebiotic and probiotic interventions decrease clinical side effects (e.g., infection and morbidity risk) in children with cancer. This study adds to the evidence that dysbiosis of the gut microbiome can be improved using

  12. The organophosphate malathion disturbs gut microbiome development and the quorum-Sensing system.

    Science.gov (United States)

    Gao, Bei; Chi, Liang; Tu, Pengcheng; Bian, Xiaoming; Thomas, Jesse; Ru, Hongyu; Lu, Kun

    2018-02-01

    The gut microbiome has tremendous potential to impact health and disease. Various environmental toxicants, including insecticides, have been shown to alter gut microbiome community structures. However, the mechanism that compositionally and functionally regulates gut microbiota remains unclear. Quorum sensing is known to modulate intra- and interspecies gene expression and coordinate population responses. It is unknown whether quorum sensing is disrupted when environmental toxicants cause perturbations in the gut microbiome community structure. To reveal the response of the quorum-sensing system to environmental exposure, we use a combination of Illumina-based 16S rRNA gene amplicon and shotgun metagenome sequencing to examine the impacts of a widely used organophosphate insecticide, malathion, on the gut microbiome trajectory, quorum sensing system and behaviors related to quorum sensing, such as motility and pathogenicity. Our results demonstrated that malathion perturbed the gut microbiome development, quorum sensing and quorum sensing related behaviors. These findings may provide a novel mechanistic understanding of the role of quorum-sensing in the gut microbiome toxicity of malathion. Copyright © 2017. Published by Elsevier B.V.

  13. The Gut Microbiome, Obesity, and Weight Control in Women's Reproductive Health.

    Science.gov (United States)

    Greathouse, K Leigh; Faucher, Mary Ann; Hastings-Tolsma, Marie

    2017-08-01

    The microbes residing in the human gut, referred to as the microbiome, are intricately linked to energy homeostasis and subsequently obesity. Integral to the origins of obesity, the microbiome is believed to affect not only health of the human gut but also overall health. This microbiome-obesity association is mediated through the process of energy extraction, metabolism, and cross talk between the brain and the gut microbiome. Host exposures, including diet, that potentially modify genetic predisposition to obesity and affect weight management are reviewed. The higher prevalence of obesity among women and recent evidence linking obesity during pregnancy with offspring health make this topic particularly relevant. Current limitations in microbiome research to address obesity and future advances in this field are described. Applications of this science with respect to applied nursing and overall health care in general are included, with emphasis on the reproductive health of women and their offspring.

  14. Human and rat gut microbiome composition is maintained following sleep restriction

    NARCIS (Netherlands)

    Zhang, Shirley L; Bai, Lei; Goel, Namni; Bailey, Aubrey; Jang, Christopher J; Bushman, Frederic D; Meerlo, Peter; Dinges, David F; Sehgal, Amita

    Insufficient sleep increasingly characterizes modern society, contributing to a host of serious medical problems. Loss of sleep is associated with metabolic diseases such as obesity and diabetes, cardiovascular disorders, and neurological and cognitive impairments. Shifts in gut microbiome

  15. Baleen whales host a unique gut microbiome with similarities to both carnivores and herbivores

    OpenAIRE

    Sanders, Jon G.; Beichman, Annabel C.; Roman, Joe; Scott, Jarrod J.; Emerson, David; McCarthy, James J.; Girguis, Peter R.

    2015-01-01

    Mammals host gut microbiomes of immense physiological consequence, but the determinants of diversity in these communities remain poorly understood. Diet appears to be the dominant factor, but host phylogeny also seems to be an important, if unpredictable, correlate. Here we show that baleen whales, which prey on animals (fish and crustaceans), harbor unique gut microbiomes with surprising parallels in functional capacity and higher level taxonomy to those of terrestrial herbivores. These simi...

  16. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity

    NARCIS (Netherlands)

    Zhernakova, A.; Kurilshikov, Alexander; Bonder, Marc Jan; Feskens, E.J.M.

    2016-01-01

    Deep sequencing of the gut microbiomes of 1135 participants from a Dutch population-based cohort shows relations between the microbiome and 126 exogenous and intrinsic host factors, including 31 intrinsic factors, 12 diseases, 19 drug groups, 4 smoking categories, and 60 dietary factors. These

  17. Omics for Understanding the Gut-Liver-Microbiome Axis and Precision Medicine.

    Science.gov (United States)

    Khalsa, Jag; Duffy, Linda C; Riscuta, Gabriela; Starke-Reed, Pamela; Hubbard, Van S

    2017-03-01

    Human metabolic disease opens a new view to understanding the contribution of the intestinal microbiome to drug metabolism and drug-induced toxicity in gut-liver function. The gut microbiome, a key determinant of intestinal inflammation, also plays a direct role in chronic inflammation and liver disease. Gut bacterial communities directly metabolize certain drugs, reducing their bioavailability and influencing individual variation in drug response. In addition, some microbiome-produced compounds may affect drug pharmacokinetics and pharmacodynamics via altered expression of metabolizing enzymes and drug transporters or genes coding for drug target proteins, drug response phenotypes, and disease states. Molecular-based high-throughput technologies are providing novel insight about host-gut microbiome interactions, homeostasis, and xenobiotic effects associated with wide variation in efficacy or toxicity in humans. It is envisioned that future approaches to treating and preventing liver disease will benefit from in-depth studies of the liver-microbiome axis. Thus, the microbiome shares a fundamental role in human physiology with various organ systems, and its importance must be considered in the rapid evolution of precision medicine. A new emerging perspective of understanding the effect of the gut microbiome on human response to drugs would be indispensable for developing efficacious, safe, and cost-effective precision therapies. © 2017, The American College of Clinical Pharmacology.

  18. “I Am I and My Bacterial Circumstances”: Linking Gut Microbiome, Neurodevelopment, and Depression

    Science.gov (United States)

    Lima-Ojeda, Juan M.; Rupprecht, Rainer; Baghai, Thomas C.

    2017-01-01

    Recently, there has been renewed interest in the role played by microbiome in both human health and human disease. A correct equilibrium between the human host and their microorganisms is important for an appropriate physiological function. Extensive research has shown that microbes that inhabit the gastrointestinal tract—or gut microbiota—are involved not only in both nutritive and digestive activities but also in immunological processes. Moreover, the gut microbiome influences both central nervous system and energy homeostasis. An altered gut microbiome has been associated with the pathophysiology of different diseases, including neuropsychiatric disorders. Apparently, both environmental—diet, exposition to antibiotics, and infections—and host-genetic factors have a strong influence on gut microbiome, modulating the risk for neuropsychiatric illness. Also, early life disruption of the microbiome–gut–brain (MGB) axis has been associated with an increased risk of developing depression later in life, suggesting a link between gut microbiome, neurodevelopment, and depression. This review aims to contribute to this growing area of research by exploring the role played by the gut microbiome in neurodevelopment and in the etiology of the depressive syndrome, including nutritional, immunological, and energy homeostasis approaches. PMID:28878696

  19. “I Am I and My Bacterial Circumstances”: Linking Gut Microbiome, Neurodevelopment, and Depression

    Directory of Open Access Journals (Sweden)

    Juan M. Lima-Ojeda

    2017-08-01

    Full Text Available Recently, there has been renewed interest in the role played by microbiome in both human health and human disease. A correct equilibrium between the human host and their microorganisms is important for an appropriate physiological function. Extensive research has shown that microbes that inhabit the gastrointestinal tract—or gut microbiota—are involved not only in both nutritive and digestive activities but also in immunological processes. Moreover, the gut microbiome influences both central nervous system and energy homeostasis. An altered gut microbiome has been associated with the pathophysiology of different diseases, including neuropsychiatric disorders. Apparently, both environmental—diet, exposition to antibiotics, and infections—and host-genetic factors have a strong influence on gut microbiome, modulating the risk for neuropsychiatric illness. Also, early life disruption of the microbiome–gut–brain (MGB axis has been associated with an increased risk of developing depression later in life, suggesting a link between gut microbiome, neurodevelopment, and depression. This review aims to contribute to this growing area of research by exploring the role played by the gut microbiome in neurodevelopment and in the etiology of the depressive syndrome, including nutritional, immunological, and energy homeostasis approaches.

  20. Structure and function of the healthy pre-adolescent pediatric gut microbiome.

    Science.gov (United States)

    Hollister, Emily B; Riehle, Kevin; Luna, Ruth Ann; Weidler, Erica M; Rubio-Gonzales, Michelle; Mistretta, Toni-Ann; Raza, Sabeen; Doddapaneni, Harsha V; Metcalf, Ginger A; Muzny, Donna M; Gibbs, Richard A; Petrosino, Joseph F; Shulman, Robert J; Versalovic, James

    2015-08-26

    The gut microbiome influences myriad host functions, including nutrient acquisition, immune modulation, brain development, and behavior. Although human gut microbiota are recognized to change as we age, information regarding the structure and function of the gut microbiome during childhood is limited. Using 16S rRNA gene and shotgun metagenomic sequencing, we characterized the structure, function, and variation of the healthy pediatric gut microbiome in a cohort of school-aged, pre-adolescent children (ages 7-12 years). We compared the healthy pediatric gut microbiome with that of healthy adults previously recruited from the same region (Houston, TX, USA). Although healthy children and adults harbored similar numbers of taxa and functional genes, their composition and functional potential differed significantly. Children were enriched in Bifidobacterium spp., Faecalibacterium spp., and members of the Lachnospiraceae, while adults harbored greater abundances of Bacteroides spp. From a functional perspective, significant differences were detected with respect to the relative abundances of genes involved in vitamin synthesis, amino acid degradation, oxidative phosphorylation, and triggering mucosal inflammation. Children's gut communities were enriched in functions which may support ongoing development, while adult communities were enriched in functions associated with inflammation, obesity, and increased risk of adiposity. Previous studies suggest that the human gut microbiome is relatively stable and adult-like after the first 1 to 3 years of life. Our results suggest that the healthy pediatric gut microbiome harbors compositional and functional qualities that differ from those of healthy adults and that the gut microbiome may undergo a more prolonged development than previously suspected.

  1. Comparative metagenomic analysis of plasmid encoded functions in the human gut microbiome

    Directory of Open Access Journals (Sweden)

    Marchesi Julian R

    2010-01-01

    Full Text Available Abstract Background Little is known regarding the pool of mobile genetic elements associated with the human gut microbiome. In this study we employed the culture independent TRACA system to isolate novel plasmids from the human gut microbiota, and a comparative metagenomic analysis to investigate the distribution and relative abundance of functions encoded by these plasmids in the human gut microbiome. Results Novel plasmids were acquired from the human gut microbiome, and homologous nucleotide sequences with high identity (>90% to two plasmids (pTRACA10 and pTRACA22 were identified in the multiple human gut microbiomes analysed here. However, no homologous nucleotide sequences to these plasmids were identified in the murine gut or environmental metagenomes. Functions encoded by the plasmids pTRACA10 and pTRACA22 were found to be more prevalent in the human gut microbiome when compared to microbial communities from other environments. Among the most prevalent functions identified was a putative RelBE toxin-antitoxin (TA addiction module, and subsequent analysis revealed that this was most closely related to putative TA modules from gut associated bacteria belonging to the Firmicutes. A broad phylogenetic distribution of RelE toxin genes was observed in gut associated bacterial species (Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria, but no RelE homologues were identified in gut associated archaeal species. We also provide indirect evidence for the horizontal transfer of these genes between bacterial species belonging to disparate phylogenetic divisions, namely Gram negative Proteobacteria and Gram positive species from the Firmicutes division. Conclusions The application of a culture independent system to capture novel plasmids from the human gut mobile metagenome, coupled with subsequent comparative metagenomic analysis, highlighted the unexpected prevalence of plasmid encoded functions in the gut microbial ecosystem. In

  2. The Gut Microbiome and Mental Health: Implications for Anxiety- and Trauma-Related Disorders.

    Science.gov (United States)

    Malan-Muller, Stefanie; Valles-Colomer, Mireia; Raes, Jeroen; Lowry, Christopher A; Seedat, Soraya; Hemmings, Sian M J

    2018-02-01

    Biological psychiatry research has long focused on the brain in elucidating the neurobiological mechanisms of anxiety- and trauma-related disorders. This review challenges this assumption and suggests that the gut microbiome and its interactome also deserve attention to understand brain disorders and develop innovative treatments and diagnostics in the 21st century. The recent, in-depth characterization of the human microbiome spurred a paradigm shift in human health and disease. Animal models strongly suggest a role for the gut microbiome in anxiety- and trauma-related disorders. The microbiota-gut-brain (MGB) axis sits at the epicenter of this new approach to mental health. The microbiome plays an important role in the programming of the hypothalamic-pituitary-adrenal (HPA) axis early in life, and stress reactivity over the life span. In this review, we highlight emerging findings of microbiome research in psychiatric disorders, focusing on anxiety- and trauma-related disorders specifically, and discuss the gut microbiome as a potential therapeutic target. 16S rRNA sequencing has enabled researchers to investigate and compare microbial composition between individuals. The functional microbiome can be studied using methods involving metagenomics, metatranscriptomics, metaproteomics, and metabolomics, as discussed in the present review. Other factors that shape the gut microbiome should be considered to obtain a holistic view of the factors at play in the complex interactome linked to the MGB. In all, we underscore the importance of microbiome science, and gut microbiota in particular, as emerging critical players in mental illness and maintenance of mental health. This new frontier of biological psychiatry and postgenomic medicine should be embraced by the mental health community as it plays an ever-increasing transformative role in integrative and holistic health research in the next decade.

  3. The Dynamics of the Human Infant Gut Microbiome in Development and in Progression Toward Type1 Diabetes

    Science.gov (United States)

    2016-09-09

    SECURITY CLASSIFICATION OF: Colonization of the fetal and infant gut microbiome results in dynamic changes in diversity, which can impact disease...susceptibility. To examine the relationship between human gut microbiome dynamics throughout infancy and type 1 diabetes (T1D), we examined a cohort of 33...unlimited. The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. The views, opinions and/or

  4. Pyrosequencing reveals the predominance of Pseudomonadaceae in gut microbiome of a Gall Midge

    Science.gov (United States)

    Gut microbes are known to play various roles in insects such as digestion of inaccessible nutrients, synthesis of deficient amino acids, and interaction with ecological environments, including host plants. Here, we analyzed the gut microbiome in Hessian fly, a serious pest of wheat. A total of 3,654...

  5. Omics for Understanding the Gut-Liver-Microbiome Axis and Precision Medicine

    Science.gov (United States)

    Human metabolic disease opens a new view to understanding the contribution of the intestinal microbiome to drug metabolism and drug-induced toxicity in gut-liver function. Gut microbiota, a key determinant of intestinal inflammation, also plays a direct role in chronic inflammation and liver disease...

  6. Imbalance of gut microbiome and intestinal epithelial barrier dysfunction in patients with high blood pressure.

    Science.gov (United States)

    Kim, Seungbum; Goel, Ruby; Kumar, Ashok; Qi, Yanfei; Lobaton, Gil; Hosaka, Koji; Mohammed, Mohammed; Handberg, Eileen M; Richards, Elaine M; Pepine, Carl J; Raizada, Mohan K

    2018-03-30

    Recent evidence indicates a link between gut pathology and microbiome with hypertension (HTN) in animal models. However, whether this association exists in humans is unknown. Thus, our objectives in the present study were to test the hypotheses that high blood pressure (BP) patients have distinct gut microbiomes and that gut-epithelial barrier function markers and microbiome composition could predict systolic BP (SBP). Fecal samples, analyzed by shotgun metagenomics, displayed taxonomic and functional changes, including altered butyrate production between patients with high BP and reference subjects. Significant increases in plasma of intestinal fatty acid binding protein (I-FABP), lipopolysaccharide (LPS), and augmented gut-targetting proinflammatory T helper 17 (Th17) cells in high BP patients demonstrated increased intestinal inflammation and permeability. Zonulin, a gut epithelial tight junction protein regulator, was markedly elevated, further supporting gut barrier dysfunction in high BP. Zonulin strongly correlated with SBP (R 2 = 0.5301, P <0.0001). Two models predicting SBP were built using stepwise linear regression analysis of microbiome data and circulating markers of gut health, and validated in a separate cohort by prediction of SBP from zonulin in plasma (R 2 = 0.4608, P <0.0001). The mouse model of HTN, chronic angiotensin II (Ang II) infusion, was used to confirm the effects of butyrate and gut barrier function on the cardiovascular system and BP. These results support our conclusion that intestinal barrier dysfunction and microbiome function are linked to HTN in humans. They suggest that manipulation of gut microbiome and its barrier functions could be the new therapeutic and diagnostic avenues for HTN. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  7. Agent Based Modeling of Human Gut Microbiome Interactions and Perturbations.

    Directory of Open Access Journals (Sweden)

    Tatiana Shashkova

    Full Text Available Intestinal microbiota plays an important role in the human health. It is involved in the digestion and protects the host against external pathogens. Examination of the intestinal microbiome interactions is required for understanding of the community influence on host health. Studies of the microbiome can provide insight on methods of improving health, including specific clinical procedures for individual microbial community composition modification and microbiota correction by colonizing with new bacterial species or dietary changes.In this work we report an agent-based model of interactions between two bacterial species and between species and the gut. The model is based on reactions describing bacterial fermentation of polysaccharides to acetate and propionate and fermentation of acetate to butyrate. Antibiotic treatment was chosen as disturbance factor and used to investigate stability of the system. System recovery after antibiotic treatment was analyzed as dependence on quantity of feedback interactions inside the community, therapy duration and amount of antibiotics. Bacterial species are known to mutate and acquire resistance to the antibiotics. The ability to mutate was considered to be a stochastic process, under this suggestion ratio of sensitive to resistant bacteria was calculated during antibiotic therapy and recovery.The model confirms a hypothesis of feedbacks mechanisms necessity for providing functionality and stability of the system after disturbance. High fraction of bacterial community was shown to mutate during antibiotic treatment, though sensitive strains could become dominating after recovery. The recovery of sensitive strains is explained by fitness cost of the resistance. The model demonstrates not only quantitative dynamics of bacterial species, but also gives an ability to observe the emergent spatial structure and its alteration, depending on various feedback mechanisms. Visual version of the model shows that spatial

  8. Tributyltin exposure induces gut microbiome dysbiosis with increased body weight gain and dyslipidemia in mice.

    Science.gov (United States)

    Guo, Hao; Yan, Haotian; Cheng, Dong; Wei, Xinglong; Kou, Ruirui; Si, Jiliang

    2018-05-03

    Gut microbiome dysbiosis plays a profound role in the pathogenesis of obesity and tributyltin (TBT) has been found as an environmental obesogen. However, whether TBT could disturb gut microbiome and the relationship between obesity induced by TBT exposure and alteration in gut microbiota are still unknown. In order to assess the association between them, mice were exposed to TBTCl (50 μg kg -1 ) once every three days from postnatal days (PNDs) 24 to 54. The results demonstrated that TBT exposure resulted in increased body weight gain, lager visceral fat accumulation and dyslipidemia in male mice on PND 84. Correspondingly, 16S rRNA gene sequencing revealed that TBT treatment decreased gut microbial species and perturbed the microbiome composition in mice. Furthermore, Pearson's corelation coefficient analysis showed a significantly negative correlation between the body weight and the alpha diversity of gut microbiome. These results suggested that TBT exposure could induce gut microbiome dysbiosis in mice, which might contribute to the obesity pathogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. A gut feeling: Microbiome-brain-immune interactions modulate social and affective behaviors.

    Science.gov (United States)

    Sylvia, Kristyn E; Demas, Gregory E

    2018-03-01

    The expression of a wide range of social and affective behaviors, including aggression and investigation, as well as anxiety- and depressive-like behaviors, involves interactions among many different physiological systems, including the neuroendocrine and immune systems. Recent work suggests that the gut microbiome may also play a critical role in modulating behavior and likely functions as an important integrator across physiological systems. Microbes within the gut may communicate with the brain via both neural and humoral pathways, providing numerous avenues of research in the area of the gut-brain axis. We are now just beginning to understand the intricate relationships among the brain, microbiome, and immune system and how they work in concert to influence behavior. The effects of different forms of experience (e.g., changes in diet, immune challenge, and psychological stress) on the brain, gut microbiome, and the immune system have often been studied independently. Though because these systems do not work in isolation, it is essential to shift our focus to the connections among them as we move forward in our investigations of the gut-brain axis, the shaping of behavioral phenotypes, and the possible clinical implications of these interactions. This review summarizes the recent progress the field has made in understanding the important role the gut microbiome plays in the modulation of social and affective behaviors, as well as some of the intricate mechanisms by which the microbiome may be communicating with the brain and immune system. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Imidacloprid decreases honey bee survival but does not affect the gut microbiome.

    Science.gov (United States)

    Raymann, Kasie; Motta, Erick V S; Girard, Catherine; Riddington, Ian M; Dinser, Jordan A; Moran, Nancy A

    2018-04-20

    Accumulating evidence suggests that pesticides have played a role in the increased rate of honeybee colony loss. One of the most commonly used pesticides in the US is the neonicotinoid imidacloprid. Although the primary mode of action of imidacloprid is the insect nervous system, it has also been shown to cause changes insects' digestive physiology, and alter the microbiota of Drosophila melanogaster larvae. The honey bee gut microbiome plays a major role in bee health. Although many studies have shown that imidacloprid affects honey bee behavior, its impact on the microbiome has not been fully elucidated. Here we investigated the impact of imidacloprid on the gut microbiome composition, survivorship of honey bees, and susceptibility to pathogens. Consistent with other studies, we show that imidacloprid exposure results in elevated mortality of honey bees in the hive and increases susceptibility to infection by pathogens. However, we did not find evidence that imidacloprid affects the gut bacterial community of honey bees. Our in vitro experiments demonstrated that honey bee gut bacteria can grow in the presence of imidacloprid, and we found some evidence that imidacloprid can be metabolized in the bee gut environment. However, none of the individual bee gut bacterial species tested could metabolize imidacloprid, suggesting that the observed metabolism of imidacloprid in vitro bee gut cultures is not caused by the gut bacteria. Overall, our results indicate that imidacloprid causes increased mortality in honey bees, but this mortality does not appear to be linked to the microbiome. Importance Growing evidence suggests that the extensive use of pesticides has played a large role in the increased rate of honey bee colony loss. Despite extensive research on the effects of imidacloprid on honey bees, it is still unknown whether it impacts the community structure of the gut microbiome. Here we investigated the impact of imidacloprid on the gut microbiome composition

  11. Dietary Interventions to Modulate the Gut Microbiome-How Far Away Are We From Precision Medicine.

    Science.gov (United States)

    De Filippis, Francesca; Vitaglione, Paola; Cuomo, Rosario; Berni Canani, Roberto; Ercolini, Danilo

    2018-04-13

    The importance of the gut microbiome in human health and disease is fully acknowledged. A perturbation in the equilibrium among the different microbial populations living in the gut (dysbiosis) has been associated with the development of several types of diseases. Modulation of the gut microbiome through dietary intervention is an emerging therapeutic and preventive strategy for many conditions. Nevertheless, interpersonal differences in response to therapeutic treatments or dietary regimens are often observed during clinical trials, and recent research has suggested that subject-specific features of the gut microbiota may be responsible. In this review, we summarize recent findings in personalized nutrition, highlighting how individualized characterization of the microbiome may assist in designing ad hoc tailored dietary intervention for disease treatment and prevention. Moreover, we discuss the limitations and challenges encountered in integrating patient-specific microbial data into clinical practice.

  12. Dynamics and stabilization of the human gut microbiome during the first year of life

    DEFF Research Database (Denmark)

    Bäckhed, Gert Fredrik; Roswall, Josefine; Peng, Yangqing

    2015-01-01

    The gut microbiota is central to human health, but its establishment in early life has not been quantitatively and functionally examined. Applying metagenomic analysis on fecal samples from a large cohort of Swedish infants and their mothers, we characterized the gut microbiome during the first...... of the microbiome. Our findings establish a framework for understanding the interplay between the gut microbiome and the human body in early life....... year of life and assessed the impact of mode of delivery and feeding on its establishment. In contrast to vaginally delivered infants, the gut microbiota of infants delivered by C-section showed significantly less resemblance to their mothers. Nutrition had a major impact on early microbiota...

  13. Gut microbiomes of mobile predators vary with landscape context and species identity

    OpenAIRE

    Tiede, Julia; Scherber, Christoph; Mutschler, James; McMahon, Katherine D.; Gratton, Claudio

    2017-01-01

    Abstract Landscape context affects predator–prey interactions and predator diet composition, yet little is known about landscape effects on insect gut microbiomes, a determinant of physiology and condition. Here, we combine laboratory and field experiments to examine the effects of landscape context on the gut bacterial community and body condition of predatory insects. Under laboratory conditions, we found that prey diversity increased bacterial richness in insect guts. In the field, we stud...

  14. The Gut Commensal Microbiome of Drosophila melanogaster Is Modified by the Endosymbiont Wolbachia.

    Science.gov (United States)

    Simhadri, Rama K; Fast, Eva M; Guo, Rong; Schultz, Michaela J; Vaisman, Natalie; Ortiz, Luis; Bybee, Joanna; Slatko, Barton E; Frydman, Horacio M

    2017-01-01

    Endosymbiotic Wolbachia bacteria and the gut microbiome have independently been shown to affect several aspects of insect biology, including reproduction, development, life span, stem cell activity, and resistance to human pathogens, in insect vectors. This work shows that Wolbachia bacteria, which reside mainly in the fly germline, affect the microbial species present in the fly gut in a lab-reared strain. Drosophila melanogaster hosts two main genera of commensal bacteria- Acetobacter and Lactobacillus . Wolbachia -infected flies have significantly reduced titers of Acetobacter . Sampling of the microbiome of axenic flies fed with equal proportions of both bacteria shows that the presence of Wolbachia bacteria is a significant determinant of the composition of the microbiome throughout fly development. However, this effect is host genotype dependent. To investigate the mechanism of microbiome modulation, the effect of Wolbachia bacteria on Imd and reactive oxygen species pathways, the main regulators of immune response in the fly gut, was measured. The presence of Wolbachia bacteria does not induce significant changes in the expression of the genes for the effector molecules in either pathway. Furthermore, microbiome modulation is not due to direct interaction between Wolbachia bacteria and gut microbes. Confocal analysis shows that Wolbachia bacteria are absent from the gut lumen. These results indicate that the mechanistic basis of the modulation of composition of the microbiome by Wolbachia bacteria is more complex than a direct bacterial interaction or the effect of Wolbachia bacteria on fly immunity. The findings reported here highlight the importance of considering the composition of the gut microbiome and host genetic background during Wolbachia -induced phenotypic studies and when formulating microbe-based disease vector control strategies. IMPORTANCE Wolbachia bacteria are intracellular bacteria present in the microbiome of a large fraction of insects

  15. The Role of the Gut Microbiome in Multiple Sclerosis Risk and Progression: Towards Characterization of the "MS Microbiome".

    Science.gov (United States)

    Pröbstel, Anne-Katrin; Baranzini, Sergio E

    2018-01-01

    Multiple sclerosis (MS) is the prototypic complex disease, in which both genes and the environment contribute to its pathogenesis. To date, > 200 independent loci across the genome have been associated with MS risk. However, these only explain a fraction of the total phenotypic variance, suggesting the possible presence of additional genetic factors, and, most likely, also environmental factors. New DNA sequencing technologies have enabled the sequencing of all kinds of microorganisms, including those living in and around humans (i.e., microbiomes). The study of bacterial populations inhabiting the gut is of particular interest in autoimmune diseases owing to their key role in shaping immune responses. In this review, we address the potential crosstalk between B cells and the gut microbiota, a relevant scenario in light of recently approved anti-B-cell therapies for MS. In addition, we review recent efforts to characterize the gut microbiome in patients with MS and discuss potential challenges and future opportunities. Finally, we describe the international MS microbiome study, a multicenter effort to study a large population of patients with MS and their healthy household partners to define the core MS microbiome, how it is shaped by disease-modifying therapies, and to explore potential therapeutic interventions.

  16. Gut microbiome and the risk factors in central nervous system autoimmunity.

    Science.gov (United States)

    Ochoa-Repáraz, Javier; Kasper, Lloyd H

    2014-11-17

    Humans are colonized after birth by microbial organisms that form a heterogeneous community, collectively termed microbiota. The genomic pool of this macro-community is named microbiome. The gut microbiota is essential for the complete development of the immune system, representing a binary network in which the microbiota interact with the host providing important immune and physiologic function and conversely the bacteria protect themselves from host immune defense. Alterations in the balance of the gut microbiome due to a combination of environmental and genetic factors can now be associated with detrimental or protective effects in experimental autoimmune diseases. These gut microbiome alterations can unbalance the gastrointestinal immune responses and influence distal effector sites leading to CNS disease including both demyelination and affective disorders. The current range of risk factors for MS includes genetic makeup and environmental elements. Of interest to this review is the consistency between this range of MS risk factors and the gut microbiome. We postulate that the gut microbiome serves as the niche where different MS risk factors merge, thereby influencing the disease process. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  17. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders

    Science.gov (United States)

    Kelly, John R.; Kennedy, Paul J.; Cryan, John F.; Dinan, Timothy G.; Clarke, Gerard; Hyland, Niall P.

    2015-01-01

    The emerging links between our gut microbiome and the central nervous system (CNS) are regarded as a paradigm shift in neuroscience with possible implications for not only understanding the pathophysiology of stress-related psychiatric disorders, but also their treatment. Thus the gut microbiome and its influence on host barrier function is positioned to be a critical node within the brain-gut axis. Mounting preclinical evidence broadly suggests that the gut microbiota can modulate brain development, function and behavior by immune, endocrine and neural pathways of the brain-gut-microbiota axis. Detailed mechanistic insights explaining these specific interactions are currently underdeveloped. However, the concept that a “leaky gut” may facilitate communication between the microbiota and these key signaling pathways has gained traction. Deficits in intestinal permeability may underpin the chronic low-grade inflammation observed in disorders such as depression and the gut microbiome plays a critical role in regulating intestinal permeability. In this review we will discuss the possible role played by the gut microbiota in maintaining intestinal barrier function and the CNS consequences when it becomes disrupted. We will draw on both clinical and preclinical evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function. PMID:26528128

  18. Insulin resistance as key factor for linking modulation of gut microbiome to health claims and dietary recommendations to tackle obesity

    NARCIS (Netherlands)

    Loman, S.; Kamp, J.W. van der

    2016-01-01

    Background: Current dietary and public health recommendations addressing obesity do not as yet include recommendations pertaining to the gut microbiome. As a corollary, no microbiome-related health claims made on foods have as yet been proposed. Scope: The MyNewGut project aims, amongst others, to

  19. Effects of moderate, voluntary ethanol consumption on the rat and human gut microbiome.

    Science.gov (United States)

    Kosnicki, Kassi L; Penprase, Jerrold C; Cintora, Patricia; Torres, Pedro J; Harris, Greg L; Brasser, Susan M; Kelley, Scott T

    2018-05-11

    Many alcohol-induced health complications are directly attributable to the toxicity of alcohol or its metabolites, but another potential health impact of alcohol may be on the microbial communities of the human gut. Clear distinctions between healthy and diseased-state gut microbiota have been observed in subjects with metabolic diseases, and recent studies suggest that chronic alcoholism is linked to gut microbiome dysbiosis. Here, we investigated the effects of moderate levels of alcohol consumption on the gut microbiome in both rats and humans. The gut microbiota of rats voluntarily consuming a 20 percent ethanol solution, on alternate days, were compared with a non-exposed control group to identify differential taxonomic and functional profiles. Gut microbial diversity profiles were determined using culture-independent amplification, next-generation sequencing and bioinformatic analysis of bacterial 16S ribosomal RNA gene sequence libraries. Our results showed that, compared with controls, ethanol-consuming rats experienced a significant decline in the biodiversity of their gut microbiomes, a state generally associated with dysbiosis. We also observed significant shifts in the overall diversity of the gut microbial communities and a dramatic change in the relative abundance of particular microbes, such as the Lactobacilli. We also compared our results to human fecal microbiome data collected as part of the citizen science American Gut Project. In contrast to the rat data, human drinkers had significantly higher gut microbial biodiversity than non-drinkers. However, we also observed that microbes that differed among the human subjects displayed similar trends in the rat model, including bacteria implicated in metabolic disease. © 2018 Society for the Study of Addiction.

  20. Plasmid metagenomics reveals multiple antibiotic resistance gene classes among the gut microbiomes of hospitalised patients

    DEFF Research Database (Denmark)

    Jitwasinkul, Tossawan; Suriyaphol, Prapat; Tangphatsornruang, Sithichoke

    2016-01-01

    Antibiotic resistance genes are rapidly spread between pathogens and the normal flora, with plasmids playing an important role in their circulation. This study aimed to investigate antibiotic resistance plasmids in the gut microbiome of hospitalised patients. Stool samples were collected from seven...... inpatients at Siriraj Hospital (Bangkok, Thailand) and were compared with a sample from a healthy volunteer. Plasmids from the gut microbiomes extracted from the stool samples were subjected to high-throughput DNA sequencing (GS Junior). Newbler-assembled DNA reads were categorised into known and unknown...... in the gut microbiome; however, it was difficult to link these to the antibiotic resistance genes identified. That the antibiotic resistance genes came from hospital and community environments is worrying....

  1. Maternal Obesity Is Associated with Alterations in the Gut Microbiome in Toddlers

    Science.gov (United States)

    Galley, Jeffrey D.; Bailey, Michael; Kamp Dush, Claire; Schoppe-Sullivan, Sarah; Christian, Lisa M.

    2014-01-01

    Children born to obese mothers are at increased risk for obesity, but the mechanisms behind this association are not fully delineated. A novel possible pathway linking maternal and child weight is the transmission of obesogenic microbes from mother to child. The current study examined whether maternal obesity was associated with differences in the composition of the gut microbiome in children in early life. Fecal samples from children 18–27 months of age (n = 77) were analyzed by pyro-tag 16S sequencing. Significant effects of maternal obesity on the composition of the gut microbiome of offspring were observed among dyads of higher socioeconomic status (SES). In the higher SES group (n = 47), children of obese (BMI≥30) versus non-obese mothers clustered on a principle coordinate analysis (PCoA) and exhibited greater homogeneity in the composition of their gut microbiomes as well as greater alpha diversity as indicated by the Shannon Diversity Index, and measures of richness and evenness. Also in the higher SES group, children born to obese versus non-obese mothers had differences in abundances of Faecalibacterium spp., Eubacterium spp., Oscillibacter spp., and Blautia spp. Prior studies have linked some of these bacterial groups to differences in weight and diet. This study provides novel evidence that maternal obesity is associated with differences in the gut microbiome in children in early life, particularly among those of higher SES. Among obese adults, the relative contribution of genetic versus behavioral factors may differ based on SES. Consequently, the extent to which maternal obesity confers measureable changes to the gut microbiome of offspring may differ based on the etiology of maternal obesity. Continued research is needed to examine this question as well as the relevance of the observed differences in gut microbiome composition for weight trajectory over the life course. PMID:25409177

  2. Maternal obesity is associated with alterations in the gut microbiome in toddlers.

    Directory of Open Access Journals (Sweden)

    Jeffrey D Galley

    Full Text Available Children born to obese mothers are at increased risk for obesity, but the mechanisms behind this association are not fully delineated. A novel possible pathway linking maternal and child weight is the transmission of obesogenic microbes from mother to child. The current study examined whether maternal obesity was associated with differences in the composition of the gut microbiome in children in early life. Fecal samples from children 18-27 months of age (n = 77 were analyzed by pyro-tag 16S sequencing. Significant effects of maternal obesity on the composition of the gut microbiome of offspring were observed among dyads of higher socioeconomic status (SES. In the higher SES group (n = 47, children of obese (BMI≥30 versus non-obese mothers clustered on a principle coordinate analysis (PCoA and exhibited greater homogeneity in the composition of their gut microbiomes as well as greater alpha diversity as indicated by the Shannon Diversity Index, and measures of richness and evenness. Also in the higher SES group, children born to obese versus non-obese mothers had differences in abundances of Faecalibacterium spp., Eubacterium spp., Oscillibacter spp., and Blautia spp. Prior studies have linked some of these bacterial groups to differences in weight and diet. This study provides novel evidence that maternal obesity is associated with differences in the gut microbiome in children in early life, particularly among those of higher SES. Among obese adults, the relative contribution of genetic versus behavioral factors may differ based on SES. Consequently, the extent to which maternal obesity confers measureable changes to the gut microbiome of offspring may differ based on the etiology of maternal obesity. Continued research is needed to examine this question as well as the relevance of the observed differences in gut microbiome composition for weight trajectory over the life course.

  3. Maternal obesity is associated with alterations in the gut microbiome in toddlers.

    Science.gov (United States)

    Galley, Jeffrey D; Bailey, Michael; Kamp Dush, Claire; Schoppe-Sullivan, Sarah; Christian, Lisa M

    2014-01-01

    Children born to obese mothers are at increased risk for obesity, but the mechanisms behind this association are not fully delineated. A novel possible pathway linking maternal and child weight is the transmission of obesogenic microbes from mother to child. The current study examined whether maternal obesity was associated with differences in the composition of the gut microbiome in children in early life. Fecal samples from children 18-27 months of age (n = 77) were analyzed by pyro-tag 16S sequencing. Significant effects of maternal obesity on the composition of the gut microbiome of offspring were observed among dyads of higher socioeconomic status (SES). In the higher SES group (n = 47), children of obese (BMI≥30) versus non-obese mothers clustered on a principle coordinate analysis (PCoA) and exhibited greater homogeneity in the composition of their gut microbiomes as well as greater alpha diversity as indicated by the Shannon Diversity Index, and measures of richness and evenness. Also in the higher SES group, children born to obese versus non-obese mothers had differences in abundances of Faecalibacterium spp., Eubacterium spp., Oscillibacter spp., and Blautia spp. Prior studies have linked some of these bacterial groups to differences in weight and diet. This study provides novel evidence that maternal obesity is associated with differences in the gut microbiome in children in early life, particularly among those of higher SES. Among obese adults, the relative contribution of genetic versus behavioral factors may differ based on SES. Consequently, the extent to which maternal obesity confers measureable changes to the gut microbiome of offspring may differ based on the etiology of maternal obesity. Continued research is needed to examine this question as well as the relevance of the observed differences in gut microbiome composition for weight trajectory over the life course.

  4. 11β-hydroxysteroid dehydrogenase-1 deficiency alters the gut microbiome response to Western diet.

    Science.gov (United States)

    Johnson, Jethro S; Opiyo, Monica N; Thomson, Marian; Gharbi, Karim; Seckl, Jonathan R; Heger, Andreas; Chapman, Karen E

    2017-02-01

    The enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD) interconverts active glucocorticoids and their intrinsically inert 11-keto forms. The type 1 isozyme, 11β-HSD1, predominantly reactivates glucocorticoids in vivo and can also metabolise bile acids. 11β-HSD1-deficient mice show altered inflammatory responses and are protected against the adverse metabolic effects of a high-fat diet. However, the impact of 11β-HSD1 on the composition of the gut microbiome has not previously been investigated. We used high-throughput 16S rDNA amplicon sequencing to characterise the gut microbiome of 11β-HSD1-deficient and C57Bl/6 control mice, fed either a standard chow diet or a cholesterol- and fat-enriched 'Western' diet. 11β-HSD1 deficiency significantly altered the composition of the gut microbiome, and did so in a diet-specific manner. On a Western diet, 11β-HSD1 deficiency increased the relative abundance of the family Bacteroidaceae, and on a chow diet, it altered relative abundance of the family Prevotellaceae Our results demonstrate that (i) genetic effects on host-microbiome interactions can depend upon diet and (ii) that alterations in the composition of the gut microbiome may contribute to the aspects of the metabolic and/or inflammatory phenotype observed with 11β-HSD1 deficiency. © 2017 The authors.

  5. The Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Sanjoy Roychowdhury

    2018-06-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is the leading cause of chronic liver disease, with prevalence increasing in parallel with the rising incidence in obesity. Believed to be a “multiple-hit” disease, several factors contribute to NAFLD initiation and progression. Of these, the gut microbiome is gaining interest as a significant factor in NAFLD prevalence. In this paper, we provide an in-depth review of the progression of NAFLD, discussing the mechanistic modes of hepatocyte injury and the potential role for manipulation of the gut microbiome as a therapeutic strategy in the prevention and treatment of NAFLD.

  6. Human and rat gut microbiome composition is maintained following sleep restriction.

    Science.gov (United States)

    Zhang, Shirley L; Bai, Lei; Goel, Namni; Bailey, Aubrey; Jang, Christopher J; Bushman, Frederic D; Meerlo, Peter; Dinges, David F; Sehgal, Amita

    2017-02-21

    Insufficient sleep increasingly characterizes modern society, contributing to a host of serious medical problems. Loss of sleep is associated with metabolic diseases such as obesity and diabetes, cardiovascular disorders, and neurological and cognitive impairments. Shifts in gut microbiome composition have also been associated with the same pathologies; therefore, we hypothesized that sleep restriction may perturb the gut microbiome to contribute to a disease state. In this study, we examined the fecal microbiome by using a cross-species approach in both rat and human studies of sleep restriction. We used DNA from hypervariable regions (V1-V2) of 16S bacteria rRNA to define operational taxonomic units (OTUs) of the microbiome. Although the OTU richness of the microbiome is decreased by sleep restriction in rats, major microbial populations are not altered. Only a single OTU, TM7-3a, was found to increase with sleep restriction of rats. In the human microbiome, we find no overt changes in the richness or composition induced by sleep restriction. Together, these results suggest that the microbiome is largely resistant to changes during sleep restriction.

  7. Perturbations of gut microbiome genes in infants with atopic dermatitis according to feeding type.

    Science.gov (United States)

    Lee, Min-Jung; Kang, Mi-Jin; Lee, So-Yeon; Lee, Eun; Kim, Kangjin; Won, Sungho; Suh, Dong In; Kim, Kyung Won; Sheen, Youn Ho; Ahn, Kangmo; Kim, Bong-Soo; Hong, Soo-Jong

    2018-04-01

    Perturbations of the infant gut microbiota can shape development of the immune system and link to the risk of allergic diseases. We sought to understand the role of the gut microbiome in patients with atopic dermatitis (AD). The metagenome of the infant gut microbiome was analyzed according to feeding types. Composition of the gut microbiota was analyzed in fecal samples from 129 infants (6 months old) by using pyrosequencing, including 66 healthy infants and 63 infants with AD. The functional profile of the gut microbiome was analyzed by means of whole-metagenome sequencing (20 control subjects and 20 patients with AD). In addition, the total number of bacteria in the feces was determined by using real-time PCR. The gut microbiome of 6-month-old infants was different based on feeding types, and 2 microbiota groups (Bifidobacterium species-dominated and Escherichia/Veillonella species-dominated groups) were found in breast-fed and mixed-fed infants. Bacterial cell amounts in the feces were lower in infants with AD than in control infants. Although no specific taxa directly correlated with AD in 16S rRNA gene results, whole-metagenome analysis revealed differences in functional genes related to immune development. The reduction in genes for oxidative phosphorylation, phosphatidylinositol 3-kinase-Akt signaling, estrogen signaling, nucleotide-binding domain-like receptor signaling, and antigen processing and presentation induced by reduced colonization of mucin-degrading bacteria (Akkermansia muciniphila, Ruminococcus gnavus, and Lachnospiraceae bacterium 2_1_58FAA) was significantly associated with stunted immune development in the AD group compared with the control group (P gut microbiome can be associated with AD because of different bacterial genes that can modulate host immune cell function. Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  8. The human gut microbiome and its dysfunctions through the meta-omics prism.

    Science.gov (United States)

    Mondot, Stanislas; Lepage, Patricia

    2016-05-01

    The microorganisms inhabiting the human gut are abundant (10(14) cells) and diverse (approximately 500 species per individual). It is now acknowledged that the microbiota has coevolved with its host to achieve a symbiotic relationship, leading to physiological homeostasis. The gut microbiota ensures vital functions, such as food digestibility, maturation of the host immune system, and protection against pathogens. Over the last few decades, the gut microbiota has also been associated with numerous diseases, such as inflammatory bowel disease, irritable bowel syndrome, obesity, and metabolic diseases. In most of these pathologies, a microbial dysbiosis has been found, indicating shifts in the taxonomic composition of the gut microbiota and changes in its functionality. Our understanding of the influence of the gut microbiota on human health is still growing. Working with microorganisms residing in the gut is challenging since most of them are anaerobic and a vast majority (approximately 75%) are uncultivable to date. Recently, a wide range of new approaches (meta-omics) has been developed to bypass the uncultivability and reveal the intricate mechanisms that sustain gut microbial homeostasis. After a brief description of these approaches (metagenomics, metatranscriptomics, metaproteomics, and metabolomics), this review will discuss the importance of considering the gut microbiome as a structured ecosystem and the use of meta-omics to decipher dysfunctions of the gut microbiome in diseases. © 2016 New York Academy of Sciences.

  9. CRISPR-Cas Systems in Bacteroides fragilis, an Important Pathobiont in the Human Gut Microbiome

    OpenAIRE

    Tajkarimi, Mehrdad; Wexler, Hannah M.

    2017-01-01

    Background: While CRISPR-Cas systems have been identified in bacteria from a wide variety of ecological niches, there are no studies to describe CRISPR-Cas elements in Bacteroides species, the most prevalent anaerobic bacteria in the lower intestinal tract. Microbes of the genus Bacteroides make up ~25% of the total gut microbiome. Bacteroides fragilis comprises only 2% of the total Bacteroides in the gut, yet causes of >70% of Bacteroides infections. The factors causing it to transition from...

  10. Gut microbiome and serum metabolome alterations in obesity and after weight-loss intervention

    DEFF Research Database (Denmark)

    Liu, Ruixin; Hong, Jie; Xu, Xiaoqiang

    2017-01-01

    Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating...... metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet...

  11. Taxonomic and predicted metabolic profiles of the human gut microbiome in pre-Columbian mummies.

    Science.gov (United States)

    Santiago-Rodriguez, Tasha M; Fornaciari, Gino; Luciani, Stefania; Dowd, Scot E; Toranzos, Gary A; Marota, Isolina; Cano, Raul J

    2016-11-01

    Characterization of naturally mummified human gut remains could potentially provide insights into the preservation and evolution of commensal and pathogenic microorganisms, and metabolic profiles. We characterized the gut microbiome of two pre-Columbian Andean mummies dating to the 10-15th centuries using 16S rRNA gene high-throughput sequencing and metagenomics, and compared them to a previously characterized gut microbiome of an 11th century AD pre-Columbian Andean mummy. Our previous study showed that the Clostridiales represented the majority of the bacterial communities in the mummified gut remains, but that other microbial communities were also preserved during the process of natural mummification, as shown with the metagenomics analyses. The gut microbiome of the other two mummies were mainly comprised by Clostridiales or Bacillales, as demonstrated with 16S rRNA gene amplicon sequencing, many of which are facultative anaerobes, possibly consistent with the process of natural mummification requiring low oxygen levels. Metagenome analyses showed the presence of other microbial groups that were positively or negatively correlated with specific metabolic profiles. The presence of sequences similar to both Trypanosoma cruzi and Leishmania donovani could suggest that these pathogens were prevalent in pre-Columbian individuals. Taxonomic and functional profiling of mummified human gut remains will aid in the understanding of the microbial ecology of the process of natural mummification. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Chemical reaction vector embeddings: towards predicting drug metabolism in the human gut microbiome.

    Science.gov (United States)

    Mallory, Emily K; Acharya, Ambika; Rensi, Stefano E; Turnbaugh, Peter J; Bright, Roselie A; Altman, Russ B

    2018-01-01

    Bacteria in the human gut have the ability to activate, inactivate, and reactivate drugs with both intended and unintended effects. For example, the drug digoxin is reduced to the inactive metabolite dihydrodigoxin by the gut Actinobacterium E. lenta, and patients colonized with high levels of drug metabolizing strains may have limited response to the drug. Understanding the complete space of drugs that are metabolized by the human gut microbiome is critical for predicting bacteria-drug relationships and their effects on individual patient response. Discovery and validation of drug metabolism via bacterial enzymes has yielded >50 drugs after nearly a century of experimental research. However, there are limited computational tools for screening drugs for potential metabolism by the gut microbiome. We developed a pipeline for comparing and characterizing chemical transformations using continuous vector representations of molecular structure learned using unsupervised representation learning. We applied this pipeline to chemical reaction data from MetaCyc to characterize the utility of vector representations for chemical reaction transformations. After clustering molecular and reaction vectors, we performed enrichment analyses and queries to characterize the space. We detected enriched enzyme names, Gene Ontology terms, and Enzyme Consortium (EC) classes within reaction clusters. In addition, we queried reactions against drug-metabolite transformations known to be metabolized by the human gut microbiome. The top results for these known drug transformations contained similar substructure modifications to the original drug pair. This work enables high throughput screening of drugs and their resulting metabolites against chemical reactions common to gut bacteria.

  13. Gut Microbiome and Putative Resistome of Inca and Italian Nobility Mummies.

    Science.gov (United States)

    Santiago-Rodriguez, Tasha M; Fornaciari, Gino; Luciani, Stefania; Toranzos, Gary A; Marota, Isolina; Giuffra, Valentina; Cano, Raul J

    2017-11-07

    Little is still known about the microbiome resulting from the process of mummification of the human gut. In the present study, the gut microbiota, genes associated with metabolism, and putative resistome of Inca and Italian nobility mummies were characterized by using high-throughput sequencing. The Italian nobility mummies exhibited a higher bacterial diversity as compared to the Inca mummies when using 16S ribosomal (rRNA) gene amplicon sequencing, but both groups showed bacterial and fungal taxa when using shotgun metagenomic sequencing that may resemble both the thanatomicrobiome and extant human gut microbiomes. Identification of sequences associated with plants, animals, and carbohydrate-active enzymes (CAZymes) may provide further insights into the dietary habits of Inca and Italian nobility mummies. Putative antibiotic-resistance genes in the Inca and Italian nobility mummies support a human gut resistome prior to the antibiotic therapy era. The higher proportion of putative antibiotic-resistance genes in the Inca compared to Italian nobility mummies may support the hypotheses that a greater exposure to the environment may result in a greater acquisition of antibiotic-resistance genes. The present study adds knowledge of the microbiome resulting from the process of mummification of the human gut, insights of ancient dietary habits, and the preserved putative human gut resistome prior the antibiotic therapy era.

  14. Gut Microbiome and Putative Resistome of Inca and Italian Nobility Mummies

    Directory of Open Access Journals (Sweden)

    Tasha M. Santiago-Rodriguez

    2017-11-01

    Full Text Available Little is still known about the microbiome resulting from the process of mummification of the human gut. In the present study, the gut microbiota, genes associated with metabolism, and putative resistome of Inca and Italian nobility mummies were characterized by using high-throughput sequencing. The Italian nobility mummies exhibited a higher bacterial diversity as compared to the Inca mummies when using 16S ribosomal (rRNA gene amplicon sequencing, but both groups showed bacterial and fungal taxa when using shotgun metagenomic sequencing that may resemble both the thanatomicrobiome and extant human gut microbiomes. Identification of sequences associated with plants, animals, and carbohydrate-active enzymes (CAZymes may provide further insights into the dietary habits of Inca and Italian nobility mummies. Putative antibiotic-resistance genes in the Inca and Italian nobility mummies support a human gut resistome prior to the antibiotic therapy era. The higher proportion of putative antibiotic-resistance genes in the Inca compared to Italian nobility mummies may support the hypotheses that a greater exposure to the environment may result in a greater acquisition of antibiotic-resistance genes. The present study adds knowledge of the microbiome resulting from the process of mummification of the human gut, insights of ancient dietary habits, and the preserved putative human gut resistome prior the antibiotic therapy era.

  15. [Review of the relation between gut microbiome, metabolic disease and hypertension].

    Science.gov (United States)

    Barna, István; Nyúl, Dóra; Szentes, Tamás; Schwab, Richárd

    2018-03-01

    Gut flora has personal characteristics for each individual, similar to the fingerprints, consisting of a special mixture of bacterial species living in the intestines, now referred to as the gut microbiome. There is a strong correlation between the loss of microbial diversity and the functional bowel disorders, obesity, type 2 diabetes and cardiovascular disease as well as many autoimmune disorders. With genetic testing of stool diversity of the gut microbiome and exact analysis of the species and phylogenetic classification of the gut flora, the changes of diversity can be identified and the overgrowth of some bacteria can be revealed. In cases with pre- and manifest hypertension, an overgrowth of species from the phylum Firmicutes has been reported along with the relative decline of the phylum Bacteroidetes as opposed with cases of normotension. At the same time, the physiological balance among bacterial families was lost. According to the first studies, there is a correlation between hypertension and the lost balance of the gut microflora, both in animal experiments and in the human clinical setting. This evidence also suggests that targeted dietary alteration of the gut microbiome can be a new innovative approach in the treatment of hypertension. Orv Hetil. 2018; 159(9): 346-351.

  16. Drunk bugs: Chronic vapour alcohol exposure induces marked changes in the gut microbiome in mice.

    Science.gov (United States)

    Peterson, Veronica L; Jury, Nicholas J; Cabrera-Rubio, Raúl; Draper, Lorraine A; Crispie, Fiona; Cotter, Paul D; Dinan, Timothy G; Holmes, Andrew; Cryan, John F

    2017-04-14

    The gut microbiota includes a community of bacteria that play an integral part in host health and biological processes. Pronounced and repeated findings have linked gut microbiome to stress, anxiety, and depression. Currently, however, there remains only a limited set of studies focusing on microbiota change in substance abuse, including alcohol use disorder. To date, no studies have investigated the impact of vapour alcohol administration on the gut microbiome. For research on gut microbiota and addiction to proceed, an understanding of how route of drug administration affects gut microbiota must first be established. Animal models of alcohol abuse have proven valuable for elucidating the biological processes involved in addiction and alcohol-related diseases. This is the first study to investigate the effect of vapour route of ethanol administration on gut microbiota in mice. Adult male C57BL/6J mice were exposed to 4 weeks of chronic intermittent vapourized ethanol (CIE, N=10) or air (Control, N=9). Faecal samples were collected at the end of exposure followed by 16S sequencing and bioinformatic analysis. Robust separation between CIE and Control was seen in the microbiome, as assessed by alpha (pgut microbiota in mice. Significant increases in genus Alistipes (pgut-brain axis and align with previous research showing similar microbiota alterations in inflammatory states during alcoholic hepatitis and psychological stress. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Spatial structure of the Mormon cricket gut microbiome and its predicted contribution to nutrition and immune function

    Science.gov (United States)

    The gut microbiome of insects plays an important role in their ecology and evolution, participating in nutrient acquisition, immunity, and behavior. Microbial community structure within the gut is heavily influenced by differences among gut regions in morphology and physiology, which determine the n...

  18. The Gut Microbiome Contributes to a Substantial Proportion of the Variation in Blood Lipids

    NARCIS (Netherlands)

    Fu, Jingyuan; Bonder, Marc Jan; Cenit, Maria Carmen; Tigchelaar-Feenstra, Ettje; Maatman, Astrid; Dekens, Jackie A. M.; Brandsma, Eelke; Marczynska, Joanna; Imhann, Floris; Weersma, Rinse K.; Franke, Lude; Poon, Tiffany W.; Xavier, Ramnik J.; Gevers, Dirk; Hofker, Marten H.; Wijmenga, Cisca; Zhernakova, Alexandra

    2015-01-01

    Rationale: Evidence suggests that the gut microbiome is involved in the development of cardiovascular disease, with the host-microbe interaction regulating immune and metabolic pathways. However, there was no firm evidence for associations between microbiota and metabolic risk factors for

  19. Measuring the gut microbiome in birds: Comparison of faecal and cloacal sampling.

    Science.gov (United States)

    Videvall, Elin; Strandh, Maria; Engelbrecht, Anel; Cloete, Schalk; Cornwallis, Charlie K

    2018-05-01

    The gut microbiomes of birds and other animals are increasingly being studied in ecological and evolutionary contexts. Numerous studies on birds and reptiles have made inferences about gut microbiota using cloacal sampling; however, it is not known whether the bacterial community of the cloaca provides an accurate representation of the gut microbiome. We examined the accuracy with which cloacal swabs and faecal samples measure the microbiota in three different parts of the gastrointestinal tract (ileum, caecum, and colon) using a case study on juvenile ostriches, Struthio camelus, and high-throughput 16S rRNA sequencing. We found that faeces were significantly better than cloacal swabs in representing the bacterial community of the colon. Cloacal samples had a higher abundance of Gammaproteobacteria and fewer Clostridia relative to the gut and faecal samples. However, both faecal and cloacal samples were poor representatives of the microbial communities in the caecum and ileum. Furthermore, the accuracy of each sampling method in measuring the abundance of different bacterial taxa was highly variable: Bacteroidetes was the most highly correlated phylum between all three gut sections and both methods, whereas Actinobacteria, for example, was only strongly correlated between faecal and colon samples. Based on our results, we recommend sampling faeces, whenever possible, as this sample type provides the most accurate assessment of the colon microbiome. The fact that neither sampling technique accurately portrayed the bacterial community of the ileum nor the caecum illustrates the difficulty in noninvasively monitoring gut bacteria located further up in the gastrointestinal tract. These results have important implications for the interpretation of avian gut microbiome studies. © 2017 John Wiley & Sons Ltd.

  20. Influence of Infant Feeding Type on Gut Microbiome Development in Hospitalized Preterm Infants

    Science.gov (United States)

    Cong, Xiaomei; Judge, Michelle; Xu, Wanli; Diallo, Ana; Janton, Susan; Brownell, Elizabeth A.; Maas, Kendra; Graf, Joerg

    2016-01-01

    Background Premature infants have a high risk for dysbiosis of the gut microbiome. Mother’s own breastmilk (MOM) has been found to favorably alter gut microbiome composition in infants born at term. Evidence about the influence of feeding type on gut microbial colonization of preterm infants is limited. Objective The purpose of this study was to explore the effect of feeding types on gut microbial colonization of preterm infants in the neonatal intensive care unit (NICU). Methods Thirty-three stable preterm infants were recruited at birth and followed-up for the first 30 days of life. Daily feeding information was used to classify infants into six groups (mother’s own milk [MOM], human donated milk [HDM], formula, MOM+HDM, MOM+Formula, and HDM+forumla) during postnatal days 0–10, 11–20, and 21–30 after birth. Stool samples were collected daily. DNA extracted from stool was used to sequence the 16S rRNA gene. Exploratory data analysis was conducted with a focus on temporal changes of microbial patterns and diversities among infants from different feeding cohorts. Prediction of gut microbial diversity from feeding type was estimated using linear mixed models. Results Preterm infants fed MOM (at least 70% of the total diet) had highest abundance of Clostridiales, Lactobacillales, and Bacillales compared to infants in other feeding groups, whereas infants fed primarily human donor milk or formula had a high abundance of Enterobacteriales compared to infants fed MOM. After controlling for gender, postnatal age, weight and birth gestational age, the diversity of gut microbiome increased over time and was constantly higher in infants fed MOM relative to infants with other feeding types (p breast milk benefits gut microbiome development of preterm infants, including balanced microbial community pattern and increased microbial diversity in early life. PMID:28252573

  1. Total Lipopolysaccharide from the Human Gut Microbiome Silences Toll-Like Receptor Signaling.

    Science.gov (United States)

    d'Hennezel, Eva; Abubucker, Sahar; Murphy, Leon O; Cullen, Thomas W

    2017-01-01

    Cohabitation of microbial communities with the host enables the formation of a symbiotic relationship that maintains homeostasis in the gut and beyond. One prevailing model suggests that this relationship relies on the capacity of host cells and tissues to remain tolerant to the strong immune stimulation generated by the microbiota such as the activation of Toll-like receptor 4 (TLR4) pathways by lipopolysaccharide (LPS). Indeed, gut microbial LPS is thought to be one of the most potent activators of innate immune signaling and an important mediator of the microbiome's influence on host physiology. In this study, we performed computational and experimental analyses of healthy human fecal samples to examine the TLR4 signaling capacity of the gut microbiota. These analyses revealed that an immunoinhibitory activity of LPS, conserved across the members of the order Bacteroidales and derived from an underacylated structural feature, silences TLR4 signaling for the entire consortium of organisms inhabiting the human gut. Comparative analysis of metagenomic data from the Human Microbiome Project and healthy-donor samples indicates that immune silencing via LPS is a microbe-intrinsic feature in all healthy adults. These findings challenge the current belief that robust TLR4 signaling is a feature of the microbiome and demonstrate that microbiome-derived LPS has the ability to facilitate host tolerance of gut microbes. These findings have broad implications for how we model host-microbe interactions and for our understanding of microbiome-linked disease. IMPORTANCE While the ability for humans to host a complex microbial ecosystem is an essential property of life, the mechanisms allowing for immune tolerance of such a large microbial load are not completely understood and are currently the focus of intense research. This study shows that an important proinflammatory pathway that is commonly triggered by pathogenic bacteria upon interaction with the host is, in fact

  2. Impact of Dietary Resistant Starch on the Human Gut Microbiome, Metaproteome, and Metabolome.

    Science.gov (United States)

    Maier, Tanja V; Lucio, Marianna; Lee, Lang Ho; VerBerkmoes, Nathan C; Brislawn, Colin J; Bernhardt, Jörg; Lamendella, Regina; McDermott, Jason E; Bergeron, Nathalie; Heinzmann, Silke S; Morton, James T; González, Antonio; Ackermann, Gail; Knight, Rob; Riedel, Katharina; Krauss, Ronald M; Schmitt-Kopplin, Philippe; Jansson, Janet K

    2017-10-17

    Diet can influence the composition of the human microbiome, and yet relatively few dietary ingredients have been systematically investigated with respect to their impact on the functional potential of the microbiome. Dietary resistant starch (RS) has been shown to have health benefits, but we lack a mechanistic understanding of the metabolic processes that occur in the gut during digestion of RS. Here, we collected samples during a dietary crossover study with diets containing large or small amounts of RS. We determined the impact of RS on the gut microbiome and metabolic pathways in the gut, using a combination of "omics" approaches, including 16S rRNA gene sequencing, metaproteomics, and metabolomics. This multiomics approach captured changes in the abundance of specific bacterial species, proteins, and metabolites after a diet high in resistant starch (HRS), providing key insights into the influence of dietary interventions on the gut microbiome. The combined data showed that a high-RS diet caused an increase in the ratio of Firmicutes to Bacteroidetes , including increases in relative abundances of some specific members of the Firmicutes and concurrent increases in enzymatic pathways and metabolites involved in lipid metabolism in the gut. IMPORTANCE This work was undertaken to obtain a mechanistic understanding of the complex interplay between diet and the microorganisms residing in the intestine. Although it is known that gut microbes play a key role in digestion of the food that we consume, the specific contributions of different microorganisms are not well understood. In addition, the metabolic pathways and resultant products of metabolism during digestion are highly complex. To address these knowledge gaps, we used a combination of molecular approaches to determine the identities of the microorganisms in the gut during digestion of dietary starch as well as the metabolic pathways that they carry out. Together, these data provide a more complete picture of

  3. Impact of Dietary Resistant Starch on the Human Gut Microbiome, Metaproteome, and Metabolome

    Energy Technology Data Exchange (ETDEWEB)

    Maier, Tanja V.; Lucio, Marianna; Lee, Lang Ho; VerBerkmoes, Nathan C.; Brislawn, Colin J.; Bernhardt, Jörg; Lamendella, Regina; McDermott, Jason E.; Bergeron, Nathalie; Heinzmann, Silke S.; Morton, James T.; González, Antonio; Ackermann, Gail; Knight, Rob; Riedel, Katharina; Krauss, Ronald M.; Schmitt-Kopplin, Philippe; Jansson, Janet K.; Moran, Mary Ann

    2017-10-17

    ABSTRACT

    Diet can influence the composition of the human microbiome, and yet relatively few dietary ingredients have been systematically investigated with respect to their impact on the functional potential of the microbiome. Dietary resistant starch (RS) has been shown to have health benefits, but we lack a mechanistic understanding of the metabolic processes that occur in the gut during digestion of RS. Here, we collected samples during a dietary crossover study with diets containing large or small amounts of RS. We determined the impact of RS on the gut microbiome and metabolic pathways in the gut, using a combination of “omics” approaches, including 16S rRNA gene sequencing, metaproteomics, and metabolomics. This multiomics approach captured changes in the abundance of specific bacterial species, proteins, and metabolites after a diet high in resistant starch (HRS), providing key insights into the influence of dietary interventions on the gut microbiome. The combined data showed that a high-RS diet caused an increase in the ratio ofFirmicutestoBacteroidetes, including increases in relative abundances of some specific members of theFirmicutesand concurrent increases in enzymatic pathways and metabolites involved in lipid metabolism in the gut.

    IMPORTANCEThis work was undertaken to obtain a mechanistic understanding of the complex interplay between diet and the microorganisms residing in the intestine. Although it is known that gut microbes play a key role in digestion of the food that we consume, the specific contributions of different microorganisms are not well understood. In addition, the metabolic pathways and resultant products of metabolism during digestion are highly complex. To address these knowledge gaps, we used a combination of molecular approaches to determine the identities of the microorganisms in the gut during digestion of dietary starch as well as the

  4. The Gut Microbiome as Therapeutic Target in Central Nervous System Diseases: Implications for Stroke.

    Science.gov (United States)

    Winek, Katarzyna; Dirnagl, Ulrich; Meisel, Andreas

    2016-10-01

    Research on commensal microbiota and its contribution to health and disease is a new and very dynamically developing field of biology and medicine. Recent experimental and clinical investigations underscore the importance of gut microbiota in the pathogenesis and course of stroke. Importantly, microbiota may influence the outcome of cerebral ischemia by modulating central nervous system antigen-specific immune responses. In this review we summarize studies linking gut microbiota with physiological function and disorders of the central nervous system. Based on these insights we speculate about targeting the gut microbiome in order to treat stroke.

  5. Review article: the gut microbiome in inflammatory bowel disease-avenues for microbial management.

    Science.gov (United States)

    McIlroy, J; Ianiro, G; Mukhopadhya, I; Hansen, R; Hold, G L

    2018-01-01

    The concept of an altered collective gut microbiota rather than identification of a single culprit is possibly the most significant development in inflammatory bowel disease research. We have entered the "omics" era, which now allows us to undertake large-scale/high-throughput microbiota analysis which may well define how we approach diagnosis and treatment of inflammatory bowel disease (IBD) in the future, with a strong steer towards personalised therapeutics. To assess current epidemiological, experimental and clinical evidence of the current status of knowledge relating to the gut microbiome, and its role in IBD, with emphasis on reviewing the evidence relating to microbial therapeutics and future microbiome modulating therapeutics. A Medline search including items 'intestinal microbiota/microbiome', 'inflammatory bowel disease', 'ulcerative colitis', 'Crohn's disease', 'faecal microbial transplantation', 'dietary manipulation' was performed. Disease remission and relapse are associated with microbial changes in both mucosal and luminal samples. In particular, a loss of species richness in Crohn's disease has been widely observed. Existing therapeutic approaches broadly fall into 3 categories, namely: accession, reduction or indirect modulation of the microbiome. In terms of microbial therapeutics, faecal microbial transplantation appears to hold the most promise; however, differences in study design/methodology mean it is currently challenging to elegantly translate results into clinical practice. Existing approaches to modulate the gut microbiome are relatively unrefined. Looking forward, the future of microbiome-modulating therapeutics looks bright with several novel strategies/technologies on the horizon. Taken collectively, it is clear that ignoring the microbiome in IBD is not an option. © 2017 John Wiley & Sons Ltd.

  6. The Gut Microbiome Feelings of the Brain: A Perspective for Non-Microbiologists

    Directory of Open Access Journals (Sweden)

    Aaron Lerner

    2017-10-01

    Full Text Available Objectives: To comprehensively review the scientific knowledge on the gut–brain axis. Methods: Various publications on the gut–brain axis, until 31 July 2017, were screened using the Medline, Google, and Cochrane Library databases. The search was performed using the following keywords: “gut-brain axis”, “gut-microbiota-brain axis”, “nutrition microbiome/microbiota”, “enteric nervous system”, “enteric glial cells/network”, “gut-brain pathways”, “microbiome immune system”, “microbiome neuroendocrine system” and “intestinal/gut/enteric neuropeptides”. Relevant articles were selected and reviewed. Results: Tremendous progress has been made in exploring the interactions between nutrients, the microbiome, and the intestinal, epithelium–enteric nervous, endocrine and immune systems and the brain. The basis of the gut–brain axis comprises of an array of multichannel sensing and trafficking pathways that are suggested to convey the enteric signals to the brain. These are mediated by neuroanatomy (represented by the vagal and spinal afferent neurons, the neuroendocrine–hypothalamic–pituitary–adrenal (HPA axis (represented by the gut hormones, immune routes (represented by multiple cytokines, microbially-derived neurotransmitters, and finally the gate keepers of the intestinal and brain barriers. Their mutual and harmonious but intricate interaction is essential for human life and brain performance. However, a failure in the interaction leads to a number of inflammatory-, autoimmune-, neurodegenerative-, metabolic-, mood-, behavioral-, cognitive-, autism-spectrum-, stress- and pain-related disorders. The limited availability of information on the mechanisms, pathways and cause-and-effect relationships hinders us from translating and implementing the knowledge from the bench to the clinic. Implications: Further understanding of this intricate field might potentially shed light on novel preventive and

  7. Differential human gut microbiome assemblages during soil-transmitted helminth infections in Indonesia and Liberia.

    Science.gov (United States)

    Rosa, Bruce A; Supali, Taniawati; Gankpala, Lincoln; Djuardi, Yenny; Sartono, Erliyani; Zhou, Yanjiao; Fischer, Kerstin; Martin, John; Tyagi, Rahul; Bolay, Fatorma K; Fischer, Peter U; Yazdanbakhsh, Maria; Mitreva, Makedonka

    2018-02-28

    The human intestine and its microbiota is the most common infection site for soil-transmitted helminths (STHs), which affect the well-being of ~ 1.5 billion people worldwide. The complex cross-kingdom interactions are not well understood. A cross-sectional analysis identified conserved microbial signatures positively or negatively associated with STH infections across Liberia and Indonesia, and longitudinal samples analysis from a double-blind randomized trial showed that the gut microbiota responds to deworming but does not transition closer to the uninfected state. The microbiomes of individuals able to self-clear the infection had more alike microbiome assemblages compared to individuals who remained infected. One bacterial taxon (Lachnospiracae) was negatively associated with infection in both countries, and 12 bacterial taxa were significantly associated with STH infection in both countries, including Olsenella (associated with reduced gut inflammation), which also significantly reduced in abundance following clearance of infection. Microbial community gene abundances were also affected by deworming. Functional categories identified as associated with STH infection included arachidonic acid metabolism; arachidonic acid is the precursor for pro-inflammatory leukotrienes that threaten helminth survival, and our findings suggest that some modulation of arachidonic acid activity in the STH-infected gut may occur through the increase of arachidonic acid metabolizing bacteria. For the first time, we identify specific members of the gut microbiome that discriminate between moderately/heavily STH-infected and non-infected states across very diverse geographical regions using two different statistical methods. We also identify microbiome-encoded biological functions associated with the STH infections, which are associated potentially with STH survival strategies, and changes in the host environment. These results provide a novel insight of the cross

  8. Variable responses of human and non-human primate gut microbiomes to a Western diet.

    Science.gov (United States)

    Amato, Katherine R; Yeoman, Carl J; Cerda, Gabriela; Schmitt, Christopher A; Cramer, Jennifer Danzy; Miller, Margret E Berg; Gomez, Andres; Turner, Trudy R; Wilson, Brenda A; Stumpf, Rebecca M; Nelson, Karen E; White, Bryan A; Knight, Rob; Leigh, Steven R

    2015-11-16

    The human gut microbiota interacts closely with human diet and physiology. To better understand the mechanisms behind this relationship, gut microbiome research relies on complementing human studies with manipulations of animal models, including non-human primates. However, due to unique aspects of human diet and physiology, it is likely that host-gut microbe interactions operate differently in humans and non-human primates. Here, we show that the human microbiome reacts differently to a high-protein, high-fat Western diet than that of a model primate, the African green monkey, or vervet (Chlorocebus aethiops sabaeus). Specifically, humans exhibit increased relative abundance of Firmicutes and reduced relative abundance of Prevotella on a Western diet while vervets show the opposite pattern. Predictive metagenomics demonstrate an increased relative abundance of genes associated with carbohydrate metabolism in the microbiome of only humans consuming a Western diet. These results suggest that the human gut microbiota has unique properties that are a result of changes in human diet and physiology across evolution or that may have contributed to the evolution of human physiology. Therefore, the role of animal models for understanding the relationship between the human gut microbiota and host metabolism must be re-focused.

  9. Quantifying Diet-Induced Metabolic Changes of the Human Gut Microbiome

    DEFF Research Database (Denmark)

    Shoaie, Saeed; Ghaffari, Pouyan; Kovatcheva-Datchary, Petia

    2015-01-01

    The human gut microbiome is known to be associated with various human disorders, but a major challenge is to go beyond association studies and elucidate causalities. Mathematical modeling of the human gut microbiome at a genome scale is a useful tool to decipher microbe-microbe, diet...... of single bacteria and whole communities in vitro. Focusing on metabolic interactions between the diet, gut microbiota, and host metabolism, we demonstrated the predictive power of the toolbox in a diet-intervention study of 45 obese and overweight individuals and validated our predictions by fecal...... and blood metabolomics data. Thus, modeling could quantitatively describe altered fecal and serum amino acid levels in response to diet intervention....

  10. Effects of Host Phylogeny and Habitats on Gut Microbiomes of Oriental River Prawn (Macrobrachium nipponense)

    Science.gov (United States)

    Chen, Po-Cheng; Weng, Francis Cheng-Hsuan; Jean, Wen Dar; Wang, Daryi

    2015-01-01

    The gut microbial community is one of the richest and most complex ecosystems on earth, and the intestinal microbes play an important role in host development and health. Next generation sequencing approaches, which rapidly produce millions of short reads that enable the investigation on a culture independent basis, are now popular for exploring microbial community. Currently, the gut microbiome in fresh water shrimp is unexplored. To explore gut microbiomes of the oriental river prawn (Macrobrachium nipponense) and investigate the effects of host genetics and habitats on the microbial composition, 454 pyrosequencing based on the 16S rRNA gene were performed. We collected six groups of samples, including M. nipponense shrimp from two populations, rivers and lakes, and one sister species (M. asperulum) as an out group. We found that Proteobacteria is the major phylum in oriental river prawn, followed by Firmicutes and Actinobacteria. Compositional analysis showed microbial divergence between the two shrimp species is higher than that between the two populations of one shrimp species collected from river and lake. Hierarchical clustering also showed that host genetics had a greater impact on the divergence of gut microbiome than host habitats. This finding was also congruent with the functional prediction from the metagenomic data implying that the two shrimp species still shared the same type of biological functions, reflecting a similar metabolic profile in their gut environments. In conclusion, this study provides the first investigation of the gut microbiome of fresh water shrimp, and supports the hypothesis of host species-specific signatures of bacterial community composition. PMID:26168244

  11. Diet and exercise orthogonally alter the gut microbiome and reveal independent associations with anxiety and cognition.

    Science.gov (United States)

    Kang, Silvia S; Jeraldo, Patricio R; Kurti, Aishe; Miller, Margret E Berg; Cook, Marc D; Whitlock, Keith; Goldenfeld, Nigel; Woods, Jeffrey A; White, Bryan A; Chia, Nicholas; Fryer, John D

    2014-09-13

    The ingestion of a high-fat diet (HFD) and the resulting obese state can exert a multitude of stressors on the individual including anxiety and cognitive dysfunction. Though many studies have shown that exercise can alleviate the negative consequences of a HFD using metabolic readouts such as insulin and glucose, a paucity of well-controlled rodent studies have been published on HFD and exercise interactions with regard to behavioral outcomes. This is a critical issue since some individuals assume that HFD-induced behavioral problems such as anxiety and cognitive dysfunction can simply be exercised away. To investigate this, we analyzed mice fed a normal diet (ND), ND with exercise, HFD diet, or HFD with exercise. We found that mice on a HFD had robust anxiety phenotypes but this was not rescued by exercise. Conversely, exercise increased cognitive abilities but this was not impacted by the HFD. Given the importance of the gut microbiome in shaping the host state, we used 16S rRNA hypervariable tag sequencing to profile our cohorts and found that HFD massively reshaped the gut microbial community in agreement with numerous published studies. However, exercise alone also caused massive shifts in the gut microbiome at nearly the same magnitude as diet but these changes were surprisingly orthogonal. Additionally, specific bacterial abundances were directly proportional to measures of anxiety or cognition. Thus, behavioral domains and the gut microbiome are both impacted by diet and exercise but in unrelated ways. These data have important implications for obesity research aimed at modifications of the gut microbiome and suggest that specific gut microbes could be used as a biomarker for anxiety or cognition or perhaps even targeted for therapy.

  12. Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender.

    Science.gov (United States)

    Cong, Xiaomei; Xu, Wanli; Janton, Susan; Henderson, Wendy A; Matson, Adam; McGrath, Jacqueline M; Maas, Kendra; Graf, Joerg

    2016-01-01

    Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU) and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs) and α-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixed-effects models showed that postnatal days, feeding types and gender were associated with the α-diversity, pPermanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types. In conclusion, infant postnatal age, gender and feeding type significantly contribute to the dynamic development of the gut microbiome in preterm infants.

  13. Faecalibacterium prausnitzii subspecies-level dysbiosis in the human gut microbiome underlying atopic dermatitis.

    Science.gov (United States)

    Song, Han; Yoo, Young; Hwang, Junghyun; Na, Yun-Cheol; Kim, Heenam Stanley

    2016-03-01

    Atopic dermatitis (AD) is a serious global epidemic associated with a modern lifestyle. Although aberrant interactions between gut microbes and the intestinal immune system have been implicated in this skin disease, the nature of the microbiome dysfunction underlying the disease remains unclear. The gut microbiome from 132 subjects, including 90 patients with AD, was analyzed by using 16S rRNA gene and metagenome sequence analyses. Reference genomes from the Human Microbiome Project and the KEGG Orthology database were used for metagenome analyses. Short-chain fatty acids in fecal samples were compared by using gas chromatographic-mass spectrometric analyses. We show that enrichment of a subspecies of the major gut species Faecalibacterium prausnitzii is strongly associated with AD. In addition, the AD microbiome was enriched in genes encoding the use of various nutrients that could be released from damaged gut epithelium, reflecting a bloom of auxotrophic bacteria. Fecal samples from patients with AD showed decreased levels of butyrate and propionate, which have anti-inflammatory effects. This is likely a consequence of an intraspecies compositional change in F prausnitzii that reduces the number of high butyrate and propionate producers, including those related to the strain A2-165, a lack of which has been implicated in patients with Crohn disease. The data suggest that feedback interactions between dysbiosis in F prausnitzii and dysregulation of gut epithelial inflammation might underlie the chronic progression of AD by resulting in impairment of the gut epithelial barrier, which ultimately leads to aberrant TH2-type immune responses to allergens in the skin. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  14. Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome

    Directory of Open Access Journals (Sweden)

    Jared D. Hoffman

    2017-09-01

    Full Text Available Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD. However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF, gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5–6 months of age and compared those to old mice (18–20 months of age by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased Firmicutes/Bacteroidetes ratio and alpha diversity. We also found impaired blood-brain barrier (BBB function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to

  15. Alternative Growth Promoters Modulate Broiler Gut Microbiome and Enhance Body Weight Gain

    Science.gov (United States)

    Salaheen, Serajus; Kim, Seon-Woo; Haley, Bradd J.; Van Kessel, Jo Ann S.; Biswas, Debabrata

    2017-01-01

    Antibiotic growth promoters (AGPs) are frequently used to enhance weight-gain in poultry production. However, there has been increasing concern over the impact of AGP on the emergence of antibiotic resistance in zoonotic bacterial pathogens in the microbial community of the poultry gut. In this study, we adopted mass-spectrophotometric, phylogenetic, and shotgun-metagenomic approaches to evaluate bioactive phenolic extracts (BPE) from blueberry (Vaccinium corymbosum) and blackberry (Rubus fruticosus) pomaces as AGP alternatives in broilers. We conducted two trials with 100 Cobb-500 broiler chicks (in each trial) in four equal groups that were provided water with no supplementation, supplemented with AGP (tylosin, neomycin sulfate, bacitracin, erythromycin, and oxytetracycline), or supplemented with 0.1 g Gallic acid equivalent (GAE)/L or 1.0 g GAE/L (during the last 72 h before euthanasia) of BPE for 6 weeks. When compared with the control group (water only), the chickens supplemented with AGP and 0.1 g GAE/L of BPE gained 9.5 and 5.8% more body weight, respectively. The microbiomes of both the AGP- and BPE-treated chickens had higher Firmicutes to Bacteroidetes ratios. AGP supplementation appeared to be associated with higher relative abundance of bacteriophages and unique cecal resistomes compared with BPE supplementation or control. Functional characterization of cecal microbiomes revealed significant animal-to-animal variation in the relative abundance of genes involved in energy and carbohydrate metabolism. These findings established a baseline upon which mechanisms of plant-based performance enhancers in regulation of animal growth can be investigated. In addition, the data will aid in designing alternate strategies to improve animal growth performance and consequently production. PMID:29123512

  16. Alternative Growth Promoters Modulate Broiler Gut Microbiome and Enhance Body Weight Gain

    Directory of Open Access Journals (Sweden)

    Serajus Salaheen

    2017-10-01

    Full Text Available Antibiotic growth promoters (AGPs are frequently used to enhance weight-gain in poultry production. However, there has been increasing concern over the impact of AGP on the emergence of antibiotic resistance in zoonotic bacterial pathogens in the microbial community of the poultry gut. In this study, we adopted mass-spectrophotometric, phylogenetic, and shotgun-metagenomic approaches to evaluate bioactive phenolic extracts (BPE from blueberry (Vaccinium corymbosum and blackberry (Rubus fruticosus pomaces as AGP alternatives in broilers. We conducted two trials with 100 Cobb-500 broiler chicks (in each trial in four equal groups that were provided water with no supplementation, supplemented with AGP (tylosin, neomycin sulfate, bacitracin, erythromycin, and oxytetracycline, or supplemented with 0.1 g Gallic acid equivalent (GAE/L or 1.0 g GAE/L (during the last 72 h before euthanasia of BPE for 6 weeks. When compared with the control group (water only, the chickens supplemented with AGP and 0.1 g GAE/L of BPE gained 9.5 and 5.8% more body weight, respectively. The microbiomes of both the AGP- and BPE-treated chickens had higher Firmicutes to Bacteroidetes ratios. AGP supplementation appeared to be associated with higher relative abundance of bacteriophages and unique cecal resistomes compared with BPE supplementation or control. Functional characterization of cecal microbiomes revealed significant animal-to-animal variation in the relative abundance of genes involved in energy and carbohydrate metabolism. These findings established a baseline upon which mechanisms of plant-based performance enhancers in regulation of animal growth can be investigated. In addition, the data will aid in designing alternate strategies to improve animal growth performance and consequently production.

  17. The microbiome-gut-brain axis in health and disease

    OpenAIRE

    Dinan, Timothy G.; Cryan, John F.

    2017-01-01

    Gut microbes are capable of producing most neurotransmitters found in the human brain. While these neurotransmitters primarily act locally in the gut, modulating the enteric nervous system, evidence is now accumulating to support the view that gut microbes through multiple mechanisms can influence central neurochemistry and behavior. This has been described as a fundamental paradigm shift in neuroscience. Bifidobacteria for example can produce and increase plasma levels of the serotonin precu...

  18. Impact of the Chromatin Remodeling Factor CHD1 on Gut Microbiome Composition of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Johanna Sebald

    Full Text Available The composition of the intestinal microbiota of Drosophila has been studied in some detail in recent years. Environmental, developmental and host-specific genetic factors influence microbiome composition in the fly. Our previous work has indicated that intestinal bacterial load can be affected by chromatin-targeted regulatory mechanisms. Here we studied a potential role of the conserved chromatin assembly and remodeling factor CHD1 in the shaping of the gut microbiome in Drosophila melanogaster. Using high-throughput sequencing of 16S rRNA gene amplicons, we found that Chd1 deletion mutant flies exhibit significantly reduced microbial diversity compared to rescued control strains. Specifically, although Acetobacteraceae dominated the microbiota of both Chd1 wild-type and mutant guts, Chd1 mutants were virtually monoassociated with this bacterial family, whereas in control flies other bacterial taxa constituted ~20% of the microbiome. We further show age-linked differences in microbial load and microbiota composition between Chd1 mutant and control flies. Finally, diet supplementation experiments with Lactobacillus plantarum revealed that, in contrast to wild-type flies, Chd1 mutant flies were unable to maintain higher L. plantarum titres over time. Collectively, these data provide evidence that loss of the chromatin remodeler CHD1 has a major impact on the gut microbiome of Drosophila melanogaster.

  19. The Treg/Th17 axis: A dynamic balance regulated by the gut microbiome

    Directory of Open Access Journals (Sweden)

    Sara eOmenetti

    2015-12-01

    Full Text Available T-helper 17 (Th17 and T-regulatory (Treg cells are frequently found at barrier surfaces, particularly within the intestinal mucosa, where they function to protect the host from pathogenic microorganisms and to restrain excessive effector T-cell responses, respectively. Despite their differing functional properties, Th17 cells and Tregs share similar developmental requirements. In fact, the fate of antigen-naïve T-cells to either Th17 or Treg lineages is finely regulated by key mediators, including TGFβ, IL-6 and all-trans retinoic acid (RA. Importantly, the intestinal microbiome also provides immunostimulatory signals, which can activate innate, and downstream adaptive, immune responses. Specific components of the gut microbiome have been implicated in the production of proinflammatory cytokines by innate immune cells, such as IL-6, IL-23, IL-1β, and the subsequent generation and expansion of Th17 cells. Similarly, commensal bacteria and their metabolites can also promote the generation of intestinal Tregs that can actively induce mucosal tolerance. As such, dysbiosis of the gut microbiome may not solely represent a consequence of gut inflammation, but rather shape the Treg/Th17 commitment and influence susceptibility to inflammatory bowel disease (IBD. In this review, we discuss Treg and Th17 cell plasticity, its dynamic regulation by the microbiome, and highlight its impact on intestinal homeostasis and disease.

  20. High-fat diet determines the composition of the murine gut microbiome independently of obesity.

    Science.gov (United States)

    Hildebrandt, Marie A; Hoffmann, Christian; Sherrill-Mix, Scott A; Keilbaugh, Sue A; Hamady, Micah; Chen, Ying-Yu; Knight, Rob; Ahima, Rexford S; Bushman, Frederic; Wu, Gary D

    2009-11-01

    The composition of the gut microbiome is affected by host phenotype, genotype, immune function, and diet. Here, we used the phenotype of RELMbeta knockout (KO) mice to assess the influence of these factors. Both wild-type and RELMbeta KO mice were lean on a standard chow diet, but, upon switching to a high-fat diet, wild-type mice became obese, whereas RELMbeta KO mice remained comparatively lean. To investigate the influence of diet, genotype, and obesity on microbiome composition, we used deep sequencing to characterize 25,790 16S rDNA sequences from uncultured bacterial communities from both genotypes on both diets. We found large alterations associated with switching to the high-fat diet, including a decrease in Bacteroidetes and an increase in both Firmicutes and Proteobacteria. This was seen for both genotypes (ie, in the presence and absence of obesity), indicating that the high-fat diet itself, and not the obese state, mainly accounted for the observed changes in the gut microbiota. The RELMbeta genotype also modestly influenced microbiome composition independently of diet. Metagenomic analysis of 537,604 sequence reads documented extensive changes in gene content because of a high-fat diet, including an increase in transporters and 2-component sensor responders as well as a general decrease in metabolic genes. Unexpectedly, we found a substantial amount of murine DNA in our samples that increased in proportion on a high-fat diet. These results demonstrate the importance of diet as a determinant of gut microbiome composition and suggest the need to control for dietary variation when evaluating the composition of the human gut microbiome.

  1. Seasonal variation in the copepod gut microbiome in the subtropical North Atlantic Ocean.

    Science.gov (United States)

    Shoemaker, Katyanne M; Moisander, Pia H

    2017-08-01

    Characterisation of marine copepod gut microbiome composition and its variability provides information on function of marine food webs, biogeochemical cycles and copepod health. Copepod gut microbiomes were investigated quarterly over two years at the Bermuda Atlantic Time-series Station in the North Atlantic Subtropical Gyre, while assessing seasonal shifts in stable and transient communities. Microbial communities were analysed using amplicon sequencing targeting the bacterial 16S rRNA V3-V4 region and the cyanobacterial ntcA gene. Persistent bacterial groups belonging to Firmicutes, Bacteroidetes and Actinobacteria were present in the copepod guts throughout the year, and showed synchronous changes, suggesting a link to variability in copepod nutritional content. The gut communities were separate from those in the seawater, suggesting the copepod gut hosts long-term, specialized communities. Major temporal variations in the gut communities during the early winter and spring, specifically a high relative abundance of Synechococcus (up to 65%), were attributed to bacterioplankton shifts in the water column, and copepod grazing on these picoplanktonic cyanobacteria. The presence of obligate and facultative anaerobes, including Clostridiales year round, suggests that anaerobic bacterial processes are common in these dynamic microhabitats in the oligotrophic open ocean. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  2. A geographically-diverse collection of 418 human gut microbiome pathway genome databases

    KAUST Repository

    Hahn, Aria S.

    2017-04-11

    Advances in high-throughput sequencing are reshaping how we perceive microbial communities inhabiting the human body, with implications for therapeutic interventions. Several large-scale datasets derived from hundreds of human microbiome samples sourced from multiple studies are now publicly available. However, idiosyncratic data processing methods between studies introduce systematic differences that confound comparative analyses. To overcome these challenges, we developed GutCyc, a compendium of environmental pathway genome databases (ePGDBs) constructed from 418 assembled human microbiome datasets using MetaPathways, enabling reproducible functional metagenomic annotation. We also generated metabolic network reconstructions for each metagenome using the Pathway Tools software, empowering researchers and clinicians interested in visualizing and interpreting metabolic pathways encoded by the human gut microbiome. For the first time, GutCyc provides consistent annotations and metabolic pathway predictions, making possible comparative community analyses between health and disease states in inflammatory bowel disease, Crohn’s disease, and type 2 diabetes. GutCyc data products are searchable online, or may be downloaded and explored locally using MetaPathways and Pathway Tools.

  3. The Microbiome in Mental Health: Potential Contribution of Gut Microbiota in Disease and Pharmacotherapy Management.

    Science.gov (United States)

    Flowers, Stephanie A; Ellingrod, Vicki L

    2015-10-01

    The gut microbiome is composed of ~10(13) -10(14) microbial cells and viruses that exist in a symbiotic bidirectional communicative relationship with the host. Bacterial functions in the gut have an important role in healthy host metabolic function, and dysbiosis can contribute to the pathology of many medical conditions. Alterations in the relationship between gut microbiota and host have gained some attention in mental health because new evidence supports the association of gut bacteria to cognitive and emotional processes. Of interest, illnesses such as major depressive disorder are disproportionately prevalent in patients with gastrointestinal illnesses such as inflammatory bowel disease, which pathologically has been strongly linked to microbiome function. Not only is the microbiome associated with the disease itself, but it may also influence the effectiveness or adverse effects associated with pharmacologic agents used to treat these disorders. This field of study may also provide new insights on how dietary agents may help manage mental illness both directly as well as though their influence on the therapeutic and adverse effects of psychotropic agents. © 2015 Pharmacotherapy Publications, Inc.

  4. Targeting friend and foe: Emerging therapeutics in the age of gut microbiome and disease.

    Science.gov (United States)

    Cho, Jin Ah; Chinnapen, Daniel J F

    2018-03-01

    Mucosal surfaces that line our gastrointestinal tract are continuously exposed to trillions of bacteria that form a symbiotic relationship and impact host health and disease. It is only beginning to be understood that the cross-talk between the host and microbiome involve dynamic changes in commensal bacterial population, secretion, and absorption of metabolites between the host and microbiome. As emerging evidence implicates dysbiosis of gut microbiota in the pathology and progression of various diseases such as inflammatory bowel disease, obesity, and allergy, conventional treatments that either overlook the microbiome in the mechanism of action, or eliminate vast populations of microbes via wide-spectrum antibiotics need to be reconsidered. It is also becoming clear the microbiome can influence the body's response to therapeutic treatments for cancers. As such, targeting the microbiome as treatment has garnered much recent attention and excitement from numerous research labs and biotechnology companies. Treatments range from fecal microbial transplantation to precision-guided molecular approaches. Here, we survey recent progress in the development of innovative therapeutics that target the microbiome to treat disease, and highlight key findings in the interplay between host microbes and therapy.

  5. Global investigation of composition and interaction networks in gut microbiomes of individuals belonging to diverse geographies and age-groups.

    Science.gov (United States)

    Yadav, Deepak; Ghosh, Tarini Shankar; Mande, Sharmila S

    2016-01-01

    Factors like ethnicity, diet and age of an individual have been hypothesized to play a role in determining the makeup of gut microbiome. In order to investigate the gut microbiome structure as well as the inter-microbial associations present therein, we have performed a comprehensive global comparative profiling of the structure (composition, relative heterogeneity and diversity) and the inter-microbial networks in the gut microbiomes of 399 individuals of eight different nationalities. The study identified certain geography-specific trends with respect to composition, intra-group heterogeneity and diversity of the gut microbiomes. Interestingly, the gut microbial association/mutual-exlusion networks were observed to exhibit several cross-geography trends. It was seen that though the composition of gut microbiomes of the American and European individuals were similar, there were distinct patterns in their microbial interaction networks. Amongst European gut-microbiomes, the co-occurrence network obtained for the Danish population was observed to be most dense. Distinct patterns were also observed within Chinese, Japanese and Indian datasets. While performing an age-wise comparison, it was observed that the microbial interactions increased with the age of individuals. Furthermore, certain bacterial groups were identified to be present only in the older age groups. The trends observed in gut microbial networks could be due to the inherent differences in the diet of individuals belonging to different nationalities. For example, the higher number of microbial associations in the Danish population as compared to the Spanish population, may be attributed to the evenly distributed diet of the later. This is in line with previously reported findings which indicate an increase in functional interdependency of microbes in individuals with higher nutritional status. To summarise, the present study identifies geography and age specific patterns in the composition as well as

  6. Gut Microbiome Developmental Patterns in Early Life of Preterm Infants: Impacts of Feeding and Gender.

    Directory of Open Access Journals (Sweden)

    Xiaomei Cong

    Full Text Available Gut microbiota plays a key role in multiple aspects of human health and disease, particularly in early life. Distortions of the gut microbiota have been found to correlate with fatal diseases in preterm infants, however, developmental patterns of gut microbiome and factors affecting the colonization progress in preterm infants remain unclear. The purpose of this prospective longitudinal study was to explore day-to-day gut microbiome patterns in preterm infants during their first 30 days of life in the neonatal intensive care unit (NICU and investigate potential factors related to the development of the infant gut microbiome. A total of 378 stool samples were collected daily from 29 stable/healthy preterm infants. DNA extracted from stool was used to sequence the V4 region of the 16S rRNA gene region for community analysis. Operational taxonomic units (OTUs and α-diversity of the community were determined using QIIME software. Proteobacteria was the most abundant phylum, accounting for 54.3% of the total reads. Result showed shift patterns of increasing Clostridium and Bacteroides, and decreasing Staphylococcus and Haemophilus over time during early life. Alpha-diversity significantly increased daily in preterm infants after birth and linear mixed-effects models showed that postnatal days, feeding types and gender were associated with the α-diversity, p< 0.05-0.01. Male infants were found to begin with a low α-diversity, whereas females tended to have a higher diversity shortly after birth. Female infants were more likely to have higher abundance of Clostridiates, and lower abundance of Enterobacteriales than males during early life. Infants fed mother's own breastmilk (MBM had a higher diversity of gut microbiome and significantly higher abundance in Clostridiales and Lactobacillales than infants fed non-MBM. Permanova also showed that bacterial compositions were different between males and females and between MBM and non-MBM feeding types

  7. Stable Engraftment of Bifidobacterium longum AH1206 in the Human Gut Depends on Individualized Features of the Resident Microbiome.

    Science.gov (United States)

    Maldonado-Gómez, María X; Martínez, Inés; Bottacini, Francesca; O'Callaghan, Amy; Ventura, Marco; van Sinderen, Douwe; Hillmann, Benjamin; Vangay, Pajau; Knights, Dan; Hutkins, Robert W; Walter, Jens

    2016-10-12

    Live bacteria (such as probiotics) have long been used to modulate gut microbiota and human physiology, but their colonization is mostly transient. Conceptual understanding of the ecological principles as they apply to exogenously introduced microbes in gut ecosystems is lacking. We find that, when orally administered to humans, Bifidobacterium longum AH1206 stably persists in the gut of 30% of individuals for at least 6 months without causing gastrointestinal symptoms or impacting the composition of the resident gut microbiota. AH1206 engraftment was associated with low abundance of resident B. longum and underrepresentation of specific carbohydrate utilization genes in the pre-treatment microbiome. Thus, phylogenetic limiting and resource availability are two factors that control the niche opportunity for AH1206 colonization. These findings suggest that bacterial species and functional genes absent in the gut microbiome of individual humans can be reestablished, providing opportunities for precise and personalized microbiome reconstitution. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Gut microbiome can control antitumor immune function in liver

    Science.gov (United States)

    An NCI study in mice that found a connection between gut bacteria and antitumor immune responses in the liver has implications for understanding mechanisms that lead to liver cancer and for potential treatments. The study was published in Science.

  9. The obese gut microbiome across the epidemiologic transition

    Directory of Open Access Journals (Sweden)

    Lara R. Dugas

    2016-01-01

    Full Text Available Abstract The obesity epidemic has emerged over the past few decades and is thought to be a result of both genetic and environmental factors. A newly identified factor, the gut microbiota, which is a bacterial ecosystem residing within the gastrointestinal tract of humans, has now been implicated in the obesity epidemic. Importantly, this bacterial community is impacted by external environmental factors through a variety of undefined mechanisms. We focus this review on how the external environment may impact the gut microbiota by considering, the host’s geographic location ‘human geography’, and behavioral factors (diet and physical activity. Moreover, we explore the relationship between the gut microbiota and obesity with these external factors. And finally, we highlight here how an epidemiologic model can be utilized to elucidate causal relationships between the gut microbiota and external environment independently and collectively, and how this will help further define this important new factor in the obesity epidemic.

  10. Diets Alter the Gut Microbiome of Crocodile Lizards

    Directory of Open Access Journals (Sweden)

    Hai-Ying Jiang

    2017-10-01

    Full Text Available The crocodile lizard is a critically endangered reptile, and serious diseases have been found in this species in recent years, especially in captive lizards. Whether these diseases are caused by changes in the gut microbiota and the effect of captivity on disease remains to be determined. Here, we examined the relationship between the gut microbiota and diet and disease by comparing the fecal microbiota of wild lizards with those of sick and healthy lizards in captivity. The gut microbiota in wild crocodile lizards was consistently dominated by Proteobacteria (∼56.4% and Bacteroidetes (∼19.1%. However, the abundance of Firmicutes (∼2.6% in the intestine of the wild crocodile lizards was distinctly lower than that in other vertebrates. In addition, the wild samples from Guangdong Luokeng Shinisaurus crocodilurus National Nature Reserve also had a high abundance of Deinococcus–Thermus while the wild samples from Guangxi Daguishan Crocodile Lizard National Nature Reserve had a high abundance of Tenericutes. The gut microbial community in loach-fed crocodile lizards was significantly different from the gut microbial community in the earthworm-fed and wild lizards. In addition, significant differences in specific bacteria were detected among groups. Notably, in the gut microbiota, the captive lizards fed earthworms resulted in enrichment of Fusobacterium, and the captive lizards fed loaches had higher abundances of Elizabethkingia, Halomonas, Morganella, and Salmonella, all of which are pathogens or opportunistic pathogens in human or other animals. However, there is no sufficient evidence that the gut microbiota contributes to either disease A or disease B. These results provide a reference for the conservation of endangered crocodile lizards and the first insight into the relationship between disease and the gut microbiota in lizards.

  11. Pathophysiology of the Gut and the Microbiome in the Host Response.

    Science.gov (United States)

    Lyons, John D; Coopersmith, Craig M

    2017-03-01

    To describe and summarize the data supporting the gut as the motor driving critical illness and multiple organ dysfunction syndrome presented at the National Institute of Child Health and Human Development MODS Workshop (March 26-27, 2015). Summary of workshop keynote presentation. Not applicable. Presented by an expert in the field, the data assessing the role of gastrointestinal dysfunction driving critical illness were described with a focus on identifying knowledge gaps and research priorities. Summary of presentation and discussion supported and supplemented by relevant literature. The understanding of gut dysfunction in critical illness has evolved greatly over time, and the gut is now often considered as the "motor" of critical illness. The association of the gut with critical illness is supported by both animal models and clinical studies. Initially, the association between gut dysfunction and critical illness focused primarily on bacterial translocation into the bloodstream. However, that work has evolved to include other gut-derived products causing distant injury via other routes (e.g., lymphatics). Additionally, alterations in the gut epithelium may be associated with critical illness and influence outcomes. Gut epithelial apoptosis, intestinal hyperpermeability, and perturbations in the intestinal mucus layer have all been associated with critical illness. Finally, there is growing evidence that the intestinal microbiome plays a crucial role in mediating pathology in critical illness. Further research is needed to better understand the role of each of these mechanisms and their contribution to multiple organ dysfunction syndrome in children.

  12. Whole gut microbiome composition of damselfish and cardinalfish before and after reef settlement.

    Science.gov (United States)

    Parris, Darren J; Brooker, Rohan M; Morgan, Michael A; Dixson, Danielle L; Stewart, Frank J

    2016-01-01

    The Pomacentridae (damselfish) and Apogonidae (cardinalfish) are among the most common fish families on coral reefs and in the aquarium trade. Members of both families undergo a pelagic larvae phase prior to settlement on the reef, where adults play key roles in benthic habitat structuring and trophic interactions. Fish-associated microbial communities (microbiomes) significantly influence fish health and ecology, yet little is known of how microbiomes change with life stage. We quantified the taxonomic (16S rRNA gene) composition of whole gut microbiomes from ten species of damselfish and two species of cardinalfish from Lizard Island, Australia, focusing specifically on comparisons between pelagic larvae prior to settlement on the reef versus post-settlement juvenile and adult individuals. On average, microbiome phylogenetic diversity increased from pre- to post-settlement, and was unrelated to the microbial composition in the surrounding water column. However, this trend varied among species, suggesting stochasticity in fish microbiome assembly. Pre-settlement fish were enriched with bacteria of the Endozoicomonaceae, Shewanellaceae, and Fusobacteriaceae, whereas settled fish harbored higher abundances of Vibrionaceae and Pasteurellaceae. Several individual operational taxonomic units, including ones related to Vibrio harveyi, Shewanella sp., and uncultured Endozoicomonas bacteria, were shared between both pre and post-settlement stages and may be of central importance in the intestinal niche across development. Richness of the core microbiome shared among pre-settlement fish was comparable to that of settled individuals, suggesting that changes in diversity with adulthood are due to the acquisition or loss of host-specific microbes. These results identify a key transition in microbiome structure across host life stage, suggesting changes in the functional contribution of microbiomes over development in two ecologically dominant reef fish families.

  13. Whole gut microbiome composition of damselfish and cardinalfish before and after reef settlement

    Directory of Open Access Journals (Sweden)

    Darren J. Parris

    2016-08-01

    Full Text Available The Pomacentridae (damselfish and Apogonidae (cardinalfish are among the most common fish families on coral reefs and in the aquarium trade. Members of both families undergo a pelagic larvae phase prior to settlement on the reef, where adults play key roles in benthic habitat structuring and trophic interactions. Fish-associated microbial communities (microbiomes significantly influence fish health and ecology, yet little is known of how microbiomes change with life stage. We quantified the taxonomic (16S rRNA gene composition of whole gut microbiomes from ten species of damselfish and two species of cardinalfish from Lizard Island, Australia, focusing specifically on comparisons between pelagic larvae prior to settlement on the reef versus post-settlement juvenile and adult individuals. On average, microbiome phylogenetic diversity increased from pre- to post-settlement, and was unrelated to the microbial composition in the surrounding water column. However, this trend varied among species, suggesting stochasticity in fish microbiome assembly. Pre-settlement fish were enriched with bacteria of the Endozoicomonaceae, Shewanellaceae, and Fusobacteriaceae, whereas settled fish harbored higher abundances of Vibrionaceae and Pasteurellaceae. Several individual operational taxonomic units, including ones related to Vibrio harveyi, Shewanella sp., and uncultured Endozoicomonas bacteria, were shared between both pre and post-settlement stages and may be of central importance in the intestinal niche across development. Richness of the core microbiome shared among pre-settlement fish was comparable to that of settled individuals, suggesting that changes in diversity with adulthood are due to the acquisition or loss of host-specific microbes. These results identify a key transition in microbiome structure across host life stage, suggesting changes in the functional contribution of microbiomes over development in two ecologically dominant reef fish

  14. The Gut Microbiome, Its Metabolome, and Their Relationship to Health and Disease.

    Science.gov (United States)

    Wu, Gary D

    2016-01-01

    Despite its importance in maintaining the health of the host, growing evidence suggests that gut microbiota may also be an important factor in the pathogenesis of various diseases. The composition of the microbiota can be influenced by many factors, including age, genetics, host environment, and diet. There are epidemiologic data associating diet with the development of inflammatory bowel disease as well as evidence that diet can influence both the form and the function of the microbiome. Based on this evidence, studies are now underway to examine the effect of defined formula diets, an effective therapeutic modality in Crohn's disease, on both the gut microbiome and its metabolome as a therapeutic probe. Diet has an impact upon both the composition and the function of the microbiota in part through small-molecule production that may influence the development of both immune-mediated and metabolic diseases. By comparing dietary intake, the gut microbiota, and the plasma metabolome in omnivores versus vegans, we provide evidence that the production of certain bacterial metabolites is constrained by the composition of the gut microbiota. In total, these results demonstrate the potential promise of dietary manipulation of the gut microbiota and its metabolome as a modality to both maintain health and treat disease. © 2016 Nestec Ltd., Vevey/S. Karger AG, Basel.

  15. Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism.

    Science.gov (United States)

    Zheng, P; Zeng, B; Zhou, C; Liu, M; Fang, Z; Xu, X; Zeng, L; Chen, J; Fan, S; Du, X; Zhang, X; Yang, D; Yang, Y; Meng, H; Li, W; Melgiri, N D; Licinio, J; Wei, H; Xie, P

    2016-06-01

    Major depressive disorder (MDD) is the result of complex gene-environment interactions. According to the World Health Organization, MDD is the leading cause of disability worldwide, and it is a major contributor to the overall global burden of disease. However, the definitive environmental mechanisms underlying the pathophysiology of MDD remain elusive. The gut microbiome is an increasingly recognized environmental factor that can shape the brain through the microbiota-gut-brain axis. We show here that the absence of gut microbiota in germ-free (GF) mice resulted in decreased immobility time in the forced swimming test relative to conventionally raised healthy control mice. Moreover, from clinical sampling, the gut microbiotic compositions of MDD patients and healthy controls were significantly different with MDD patients characterized by significant changes in the relative abundance of Firmicutes, Actinobacteria and Bacteroidetes. Fecal microbiota transplantation of GF mice with 'depression microbiota' derived from MDD patients resulted in depression-like behaviors compared with colonization with 'healthy microbiota' derived from healthy control individuals. Mice harboring 'depression microbiota' primarily exhibited disturbances of microbial genes and host metabolites involved in carbohydrate and amino acid metabolism. This study demonstrates that dysbiosis of the gut microbiome may have a causal role in the development of depressive-like behaviors, in a pathway that is mediated through the host's metabolism.

  16. Prebiotics Mediate Microbial Interactions in a Consortium of the Infant Gut Microbiome.

    Science.gov (United States)

    Medina, Daniel A; Pinto, Francisco; Ovalle, Aline; Thomson, Pamela; Garrido, Daniel

    2017-10-04

    Composition of the gut microbiome is influenced by diet. Milk or formula oligosaccharides act as prebiotics, bioactives that promote the growth of beneficial gut microbes. The influence of prebiotics on microbial interactions is not well understood. Here we investigated the transformation of prebiotics by a consortium of four representative species of the infant gut microbiome, and how their interactions changed with dietary substrates. First, we optimized a culture medium resembling certain infant gut parameters. A consortium containing Bifidobacterium longum subsp. infantis , Bacteroides vulgatus , Escherichia coli and Lactobacillus acidophilus was grown on fructooligosaccharides (FOS) or 2'-fucosyllactose (2FL) in mono- or co-culture. While Bi. infantis and Ba. vulgatus dominated growth on 2FL, their combined growth was reduced. Besides, interaction coefficients indicated strong competition, especially on FOS. While FOS was rapidly consumed by the consortium, B. infantis was the only microbe displaying significant consumption of 2FL. Acid production by the consortium resembled the metabolism of microorganisms dominating growth in each substrate. Finally, the consortium was tested in a bioreactor, observing similar predominance but more pronounced acid production and substrate consumption. This study indicates that the chemical nature of prebiotics modulate microbial interactions in a consortium of infant gut species.

  17. Host Genotype and Gut Microbiome Modulate Insulin Secretion and Diet-Induced Metabolic Phenotypes.

    Science.gov (United States)

    Kreznar, Julia H; Keller, Mark P; Traeger, Lindsay L; Rabaglia, Mary E; Schueler, Kathryn L; Stapleton, Donald S; Zhao, Wen; Vivas, Eugenio I; Yandell, Brian S; Broman, Aimee Teo; Hagenbuch, Bruno; Attie, Alan D; Rey, Federico E

    2017-02-14

    Genetic variation drives phenotypic diversity and influences the predisposition to metabolic disease. Here, we characterize the metabolic phenotypes of eight genetically distinct inbred mouse strains in response to a high-fat/high-sucrose diet. We found significant variation in diabetes-related phenotypes and gut microbiota composition among the different mouse strains in response to the dietary challenge and identified taxa associated with these traits. Follow-up microbiota transplant experiments showed that altering the composition of the gut microbiota modifies strain-specific susceptibility to diet-induced metabolic disease. Animals harboring microbial communities with enhanced capacity for processing dietary sugars and for generating hydrophobic bile acids showed increased susceptibility to metabolic disease. Notably, differences in glucose-stimulated insulin secretion between different mouse strains were partially recapitulated via gut microbiota transfer. Our results suggest that the gut microbiome contributes to the genetic and phenotypic diversity observed among mouse strains and provide a link between the gut microbiome and insulin secretion. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. Prebiotics Mediate Microbial Interactions in a Consortium of the Infant Gut Microbiome

    Directory of Open Access Journals (Sweden)

    Daniel A. Medina

    2017-10-01

    Full Text Available Composition of the gut microbiome is influenced by diet. Milk or formula oligosaccharides act as prebiotics, bioactives that promote the growth of beneficial gut microbes. The influence of prebiotics on microbial interactions is not well understood. Here we investigated the transformation of prebiotics by a consortium of four representative species of the infant gut microbiome, and how their interactions changed with dietary substrates. First, we optimized a culture medium resembling certain infant gut parameters. A consortium containing Bifidobacterium longum subsp. infantis, Bacteroides vulgatus, Escherichia coli and Lactobacillus acidophilus was grown on fructooligosaccharides (FOS or 2′-fucosyllactose (2FL in mono- or co-culture. While Bi. infantis and Ba. vulgatus dominated growth on 2FL, their combined growth was reduced. Besides, interaction coefficients indicated strong competition, especially on FOS. While FOS was rapidly consumed by the consortium, B. infantis was the only microbe displaying significant consumption of 2FL. Acid production by the consortium resembled the metabolism of microorganisms dominating growth in each substrate. Finally, the consortium was tested in a bioreactor, observing similar predominance but more pronounced acid production and substrate consumption. This study indicates that the chemical nature of prebiotics modulate microbial interactions in a consortium of infant gut species.

  19. The Infant Gut Microbiome: Evidence for Obesity Risk and Dietary Intervention

    Science.gov (United States)

    Koleva, Petya T.; Bridgman, Sarah L.; Kozyrskyj, Anita L.

    2015-01-01

    Increasing globally, particularly in children, obesity is a serious public health issue and risk factor for overweight and metabolic disease in later life. Both in experimental animal and human studies, advances in gene sequencing technologies have yielded intriguing possibilities for the role of the gut microbiome in later development of overweight status. Before translating study findings into practice, we must first reconcile inconsistencies between animal experimentation, and human adult and infant studies. Recent evidence for associations with gut microbiota and infant weight gain or child weight status, implicate Bacteroides and Lactobacillus species. Dietary manipulation with human milk and pre/probiotic formulations holds promise for preventing obesity. PMID:25835047

  20. The Infant Gut Microbiome: Evidence for Obesity Risk and Dietary Intervention

    Directory of Open Access Journals (Sweden)

    Petya T. Koleva

    2015-03-01

    Full Text Available Increasing globally, particularly in children, obesity is a serious public health issue and risk factor for overweight and metabolic disease in later life. Both in experimental animal and human studies, advances in gene sequencing technologies have yielded intriguing possibilities for the role of the gut microbiome in later development of overweight status. Before translating study findings into practice, we must first reconcile inconsistencies between animal experimentation, and human adult and infant studies. Recent evidence for associations with gut microbiota and infant weight gain or child weight status, implicate Bacteroides and Lactobacillus species. Dietary manipulation with human milk and pre/probiotic formulations holds promise for preventing obesity.

  1. Towards understanding the trajectory and interactions of the gut microbiome in healthy older humans

    DEFF Research Database (Denmark)

    Castro Mejia, Josue Leonardo

    The human gastrointestinal tract (GIT) is inhabited by a vast amount of microorganisms from different domains of life collectively denominated the gut microbiome (GM). Among its numerous functions, GM plays a crucial role in developing the immune system in early-life and contributes to maintain...... by food-selectivity (pickiness) and associated patterns of carbohydrates’ consumption (and total energy), reflecting changes in GM composition that corresponded with signs of glucoseintolerance. Lastly, in order to gain understanding on the role of viral communities in the gut of older adults, we...

  2. Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice

    DEFF Research Database (Denmark)

    Livanos, Alexandra E; Greiner, Thomas U; Vangay, Pajau

    2016-01-01

    The early life microbiome plays important roles in host immunological and metabolic development. Because the incidence of type 1 diabetes (T1D) has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota, which predisposes to disease....... PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression. These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression and T-cell populations, accelerating T1D onset in non-obese diabetic...

  3. Characterization of the SOS meta-regulon in the human gut microbiome.

    Science.gov (United States)

    Cornish, Joseph P; Sanchez-Alberola, Neus; O'Neill, Patrick K; O'Keefe, Ronald; Gheba, Jameel; Erill, Ivan

    2014-05-01

    Data from metagenomics projects remain largely untapped for the analysis of transcriptional regulatory networks. Here, we provide proof-of-concept that metagenomic data can be effectively leveraged to analyze regulatory networks by characterizing the SOS meta-regulon in the human gut microbiome. We combine well-established in silico and in vitro techniques to mine the human gut microbiome data and determine the relative composition of the SOS network in a natural setting. Our analysis highlights the importance of translesion synthesis as a primary function of the SOS response. We predict the association of this network with three novel protein clusters involved in cell wall biogenesis, chromosome partitioning and restriction modification, and we confirm binding of the SOS response transcriptional repressor to sites in the promoter of a cell wall biogenesis enzyme, a phage integrase and a death-on-curing protein. We discuss the implications of these findings and the potential for this approach for metagenome analysis.

  4. Alterations of the murine gut microbiome in allergic airway disease are independent of surfactant protein D

    DEFF Research Database (Denmark)

    Barfod, Kenneth Klingenberg; Roggenbuck, Michael; Al-Shuweli, Suzan

    2017-01-01

    Background SP-D is an important host defense lectin in innate immunity and SP-D deficient mice show several abnormal immune effects and are susceptible to allergen-induced airway disease. At the same time, host microbiome interactions play an important role in the development of allergic airway...... disease, and alterations to gut microbiota have been linked to airway disease through the gut-lung axis. Currently, it is unknown if the genotype (Sftpd-/- or Sftpd+/+) of the standard SP-D mouse model can affect the host microbiota to such an degree that it would overcome the cohousing effect...... on microbiota and interfere with the interpretation of immunological data from the model. Generally, little is known about the effect of the SP-D protein in itself and in combination with airway disease on the microbiota. In this study, we tested the hypothesis that microbiome composition would change...

  5. Space-type radiation induces multimodal responses in the mouse gut microbiome and metabolome.

    Science.gov (United States)

    Casero, David; Gill, Kirandeep; Sridharan, Vijayalakshmi; Koturbash, Igor; Nelson, Gregory; Hauer-Jensen, Martin; Boerma, Marjan; Braun, Jonathan; Cheema, Amrita K

    2017-08-18

    Space travel is associated with continuous low dose rate exposure to high linear energy transfer (LET) radiation. Pathophysiological manifestations after low dose radiation exposure are strongly influenced by non-cytocidal radiation effects, including changes in the microbiome and host gene expression. Although the importance of the gut microbiome in the maintenance of human health is well established, little is known about the role of radiation in altering the microbiome during deep-space travel. Using a mouse model for exposure to high LET radiation, we observed substantial changes in the composition and functional potential of the gut microbiome. These were accompanied by changes in the abundance of multiple metabolites, which were related to the enzymatic activity of the predicted metagenome by means of metabolic network modeling. There was a complex dynamic in microbial and metabolic composition at different radiation doses, suggestive of transient, dose-dependent interactions between microbial ecology and signals from the host's cellular damage repair processes. The observed radiation-induced changes in microbiota diversity and composition were analyzed at the functional level. A constitutive change in activity was found for several pathways dominated by microbiome-specific enzymatic reactions like carbohydrate digestion and absorption and lipopolysaccharide biosynthesis, while the activity in other radiation-responsive pathways like phosphatidylinositol signaling could be linked to dose-dependent changes in the abundance of specific taxa. The implication of microbiome-mediated pathophysiology after low dose ionizing radiation may be an unappreciated biologic hazard of space travel and deserves experimental validation. This study provides a conceptual and analytical basis of further investigations to increase our understanding of the chronic effects of space radiation on human health, and points to potential new targets for intervention in adverse radiation

  6. Impact of Age, Caloric Restriction, and Influenza Infection on Mouse Gut Microbiome: An Exploratory Study of the Role of Age-Related Microbiome Changes on Influenza Responses

    OpenAIRE

    Jenna M. Bartley; Jenna M. Bartley; Xin Zhou; Xin Zhou; George A. Kuchel; George A. Kuchel; George M. Weinstock; George M. Weinstock; Laura Haynes; Laura Haynes

    2017-01-01

    Immunosenescence refers to age-related declines in the capacity to respond to infections such as influenza (flu). Caloric restriction represents a known strategy to slow many aging processes, including those involving the immune system. More recently, some changes in the microbiome have been described with aging, while the gut microbiome appears to influence responses to flu vaccination and infection. With these considerations in mind, we used a well-established mouse model of flu infection t...

  7. The Gut Microbiome of the Vector Lutzomyia longipalpis Is Essential for Survival of Leishmania infantum.

    Science.gov (United States)

    Kelly, Patrick H; Bahr, Sarah M; Serafim, Tiago D; Ajami, Nadim J; Petrosino, Joseph F; Meneses, Claudio; Kirby, John R; Valenzuela, Jesus G; Kamhawi, Shaden; Wilson, Mary E

    2017-01-17

    The vector-borne disease leishmaniasis, caused by Leishmania species protozoa, is transmitted to humans by phlebotomine sand flies. Development of Leishmania to infective metacyclic promastigotes in the insect gut, a process termed metacyclogenesis, is an essential prerequisite for transmission. Based on the hypothesis that vector gut microbiota influence the development of virulent parasites, we sequenced midgut microbiomes in the sand fly Lutzomyia longipalpis with or without Leishmania infantum infection. Sucrose-fed sand flies contained a highly diverse, stable midgut microbiome. Blood feeding caused a decrease in microbial richness that eventually recovered. However, bacterial richness progressively decreased in L. infantum-infected sand flies. Acetobacteraceae spp. became dominant and numbers of Pseudomonadaceae spp. diminished coordinately as the parasite underwent metacyclogenesis and parasite numbers increased. Importantly, antibiotic-mediated perturbation of the midgut microbiome rendered sand flies unable to support parasite growth and metacyclogenesis. Together, these data suggest that the sand fly midgut microbiome is a critical factor for Leishmania growth and differentiation to its infective state prior to disease transmission. Leishmania infantum, a parasitic protozoan causing fatal visceral leishmaniasis, is transmitted to humans through the bite of the sand fly Lutzomyia longipalpis Development of the parasite to its virulent metacyclic state occurs in the sand fly gut. In this study, the microbiota within the Lu. longipalpis midgut was delineated by 16S ribosomal DNA (rDNA) sequencing, revealing a highly diverse community composition that lost diversity as parasites developed to their metacyclic state and increased in abundance in infected flies. Perturbing sand fly gut microbiota with an antibiotic cocktail, which alone had no effect on either the parasite or the fly, arrested both the development of virulent parasites and parasite expansion

  8. Boolean analysis reveals systematic interactions among low-abundance species in the human gut microbiome.

    Directory of Open Access Journals (Sweden)

    Jens Christian Claussen

    2017-06-01

    Full Text Available The analysis of microbiome compositions in the human gut has gained increasing interest due to the broader availability of data and functional databases and substantial progress in data analysis methods, but also due to the high relevance of the microbiome in human health and disease. While most analyses infer interactions among highly abundant species, the large number of low-abundance species has received less attention. Here we present a novel analysis method based on Boolean operations applied to microbial co-occurrence patterns. We calibrate our approach with simulated data based on a dynamical Boolean network model from which we interpret the statistics of attractor states as a theoretical proxy for microbiome composition. We show that for given fractions of synergistic and competitive interactions in the model our Boolean abundance analysis can reliably detect these interactions. Analyzing a novel data set of 822 microbiome compositions of the human gut, we find a large number of highly significant synergistic interactions among these low-abundance species, forming a connected network, and a few isolated competitive interactions.

  9. Gut microbiota and obesity: lessons from the microbiome.

    Science.gov (United States)

    Cani, Patrice D

    2013-07-01

    The distal gut harbours microbial communities that outnumber our own eukaryotic cells. The contribution of the gut microbiota to the development of several diseases (e.g. obesity, type 2 diabetes, steatosis, cardiovascular diseases and inflammatory bowel diseases) is becoming clear, although the causality remains to be proven in humans. Global changes in the gut microbiota have been observed by a number of culture-dependent and culture-independent methods, and while the latter have mostly included 16S ribosomal RNA gene analyses, more recent studies have utilized DNA sequencing of whole-microbial communities. Altogether, these high-throughput methods have facilitated the identification of novel candidate bacteria and, most importantly, metabolic functions that might be associated with obesity and type 2 diabetes. This review discusses the association between specific taxa and obesity, together with the techniques that are used to characterize the gut microbiota in the context of obesity and type 2 diabetes. Recent results are discussed in the framework of the interactions between gut microbiota and host metabolism.

  10. Gut microbiome of the Hadza hunter-gatherers.

    Science.gov (United States)

    Schnorr, Stephanie L; Candela, Marco; Rampelli, Simone; Centanni, Manuela; Consolandi, Clarissa; Basaglia, Giulia; Turroni, Silvia; Biagi, Elena; Peano, Clelia; Severgnini, Marco; Fiori, Jessica; Gotti, Roberto; De Bellis, Gianluca; Luiselli, Donata; Brigidi, Patrizia; Mabulla, Audax; Marlowe, Frank; Henry, Amanda G; Crittenden, Alyssa N

    2014-04-15

    Human gut microbiota directly influences health and provides an extra means of adaptive potential to different lifestyles. To explore variation in gut microbiota and to understand how these bacteria may have co-evolved with humans, here we investigate the phylogenetic diversity and metabolite production of the gut microbiota from a community of human hunter-gatherers, the Hadza of Tanzania. We show that the Hadza have higher levels of microbial richness and biodiversity than Italian urban controls. Further comparisons with two rural farming African groups illustrate other features unique to Hadza that can be linked to a foraging lifestyle. These include absence of Bifidobacterium and differences in microbial composition between the sexes that probably reflect sexual division of labour. Furthermore, enrichment in Prevotella, Treponema and unclassified Bacteroidetes, as well as a peculiar arrangement of Clostridiales taxa, may enhance the Hadza's ability to digest and extract valuable nutrition from fibrous plant foods.

  11. Evaluating the impact of domestication and captivity on the horse gut microbiome.

    Science.gov (United States)

    Metcalf, Jessica L; Song, Se Jin; Morton, James T; Weiss, Sophie; Seguin-Orlando, Andaine; Joly, Frédéric; Feh, Claudia; Taberlet, Pierre; Coissac, Eric; Amir, Amnon; Willerslev, Eske; Knight, Rob; McKenzie, Valerie; Orlando, Ludovic

    2017-11-14

    The mammal gut microbiome, which includes host microbes and their respective genes, is now recognized as an essential second genome that provides critical functions to the host. In humans, studies have revealed that lifestyle strongly influences the composition and diversity of the gastrointestinal microbiome. We hypothesized that these trends in humans may be paralleled in mammals subjected to anthropogenic forces such as domestication and captivity, in which diets and natural life histories are often greatly modified. We investigated fecal microbiomes of Przewalski's horse (PH; Equus ferus przewalskii), the only horses alive today not successfully domesticated by humans, and herded, domestic horse (E. f. caballus) living in adjacent natural grasslands. We discovered PH fecal microbiomes hosted a distinct and more diverse community of bacteria compared to domestic horses, which is likely partly explained by different plant diets as revealed by trnL maker data. Within the PH population, four individuals were born in captivity in European zoos and hosted a strikingly low diversity of fecal microbiota compared to individuals born in natural reserves in France and Mongolia. These results suggest that anthropogenic forces can dramatically reshape equid gastrointestinal microbiomes, which has broader implications for the conservation management of endangered mammals.

  12. On Growth and Form of the Zebrafish Gut Microbiome

    Science.gov (United States)

    Jemielita, Matthew; Taormina, Michael; Rolig, Annah; Burns, Adam; Hampton, Jennifer; Guillemin, Karen; Parthasarathy, Raghuveer

    2014-03-01

    The vertebrate gut is home to a diverse microbial community whose composition has a strong influence on the development and health of the host organism. Researchers can identify the members of the microbiota, yet little is known about the spatial and temporal dynamics of these microbial communities, including the mechanisms guiding their nucleation, growth, and interactions. We address these issues using the larval zebrafish (Danio rerio) as a model organism, which are raised microbe-free and then inoculated with controlled compositions of fluorophore-expressing bacteria. Live imaging using light sheet fluorescence microscopy enables visualization of the gut's entire microbial population over the first 24 hours of colonization. Image analysis allows us to quantify microbial populations that range from a few individuals to tens of thousands of microbes, and analyze the structure and growth kinetics of gut bacterial communities. We find that genetically-identical microbes can show surprisingly different growth rates and colonization abilities depending on their order of arrival. This demonstrates that knowing only the constituents of the gut community is insufficient to determine their dynamics; rather, the history of colonization matters.

  13. Brain gut microbiome interactions and functional bowel disorders

    Science.gov (United States)

    Alterations in the bidirectional interactions between the intestine and the nervous system have important roles in the pathogenesis of irritable bowel syndrome (IBS). A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. A small and poorly defined r...

  14. Bisphenol A alters gut microbiome: Comparative metagenomics analysis.

    Science.gov (United States)

    Lai, Keng-Po; Chung, Yan-Tung; Li, Rong; Wan, Hin-Ting; Wong, Chris Kong-Chu

    2016-11-01

    Mounting evidence has shown that an alteration of the gut microbiota is associated with diet, and plays an important role in animal health and metabolic diseases. However, little is known about the influence of environmental contaminants on the gut microbial community. Bisphenol A (BPA), which is widely used for manufacturing plastic products, has recently been classified as an environmental obesogen. Although many studies have demonstrated the metabolic-disrupting effects of BPA on liver and pancreatic functions, the possible effects of this synthetic compound on the metabolic diversity of the intestinal microbiota is unknown. Using 16S rRNA gene sequencing analysis on caecum samples of CD-1 mice, the present study aimed to test the hypothesis that dietary BPA intake may influence the gut microbiota composition and functions, an important attributing factor to development of the metabolic syndrome. A high-fat diet (HFD) and high-sucrose diet (HSD) were included as the positive controls for comparing the changes in the intestinal microbial profiles. Our results demonstrated a significant reduction of species diversity in the gut microbiota of BPA-fed mice. Alpha and beta diversity analyses showed that dietary BPA intake led to a similar gut microbial community structure as that induced by HFD and HSD in mice. In addition, comparative analysis of the microbial communities revealed that both BPA and a HFD favored the growth of Proteobacteria, a microbial marker of dysbiosis. Consistently, growth induction of the family Helicobacteraceae and reduction of the Firmicutes and Clostridia populations were observed in the mice fed BPA or a HFD. Collectively, our study highlighted that the effects of dietary BPA intake on the shift of microbial community structure were similar to those of a HFD and HSD, and revealed microbial markers for the development of diseases associated with an unstable microbiota. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. The gut microbiome of hooded cranes (Grus monacha) wintering at Shengjin Lake, China.

    Science.gov (United States)

    Zhao, Guanghong; Zhou, Lizhi; Dong, Yuanqiu; Cheng, Yuanyuan; Song, Yunwei

    2017-06-01

    Gut microbes of animals play critical roles in processes such as digestion and immunity. Therefore, identifying gut microbes will shed light on understanding the annual life of animal species, particularly those that are threatened or endangered. In the present study, we conducted nucleotide sequence analyses of the 16S rRNA genes of gut microbiome of the hooded cranes (Grus monacha) wintering at Shengjin Lake, China, by Illumina high-throughput sequencing technology. We acquired 503,398 high-quality sequences and 785 operational taxonomic units (OTUs) from 15 fecal samples from different cranes, representing 22 phyla that were dominated by Firmicutes, Proteobacteria, and Actinobacteria. A total of 305 genera were identified that were dominated by Clostridium, Lysinibacillus, and Enterobacter. The core gut microbiome comprised 26 genera, including many probiotic species such as Clostridium, Bacillus, Cellulosilyticum, and Cellulomonas that could catabolize cellulose. The findings reported here contribute to our knowledge of the microbiology of hooded cranes and will likely advance efforts to protect waterbirds that inhabit Shengjin Lake Reserve during winter. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  16. Gut microbiome composition and metabolomic profiles of wild western lowland gorillas (Gorilla gorilla gorilla) reflect host ecology.

    Science.gov (United States)

    Gomez, Andres; Petrzelkova, Klara; Yeoman, Carl J; Vlckova, Klara; Mrázek, Jakub; Koppova, Ingrid; Carbonero, Franck; Ulanov, Alexander; Modry, David; Todd, Angelique; Torralba, Manolito; Nelson, Karen E; Gaskins, H Rex; Wilson, Brenda; Stumpf, Rebecca M; White, Bryan A; Leigh, Steven R

    2015-05-01

    The metabolic activities of gut microbes significantly influence host physiology; thus, characterizing the forces that modulate this micro-ecosystem is key to understanding mammalian biology and fitness. To investigate the gut microbiome of wild primates and determine how these microbial communities respond to the host's external environment, we characterized faecal bacterial communities and, for the first time, gut metabolomes of four wild lowland gorilla groups in the Dzanga-Sangha Protected Areas, Central African Republic. Results show that geographical range may be an important modulator of the gut microbiomes and metabolomes of these gorilla groups. Distinctions seemed to relate to feeding behaviour, implying energy harvest through increased fruit consumption or fermentation of highly fibrous foods. These observations were supported by differential abundance of metabolites and bacterial taxa associated with the metabolism of cellulose, phenolics, organic acids, simple sugars, lipids and sterols between gorillas occupying different geographical ranges. Additionally, the gut microbiomes of a gorilla group under increased anthropogenic pressure could always be distinguished from that of all other groups. By characterizing the interplay between environment, behaviour, diet and symbiotic gut microbes, we present an alternative perspective on primate ecology and on the forces that shape the gut microbiomes of wild primates from an evolutionary context. © 2015 John Wiley & Sons Ltd.

  17. Honey Bee Gut Microbiome Is Altered by In-Hive Pesticide Exposures.

    Science.gov (United States)

    Kakumanu, Madhavi L; Reeves, Alison M; Anderson, Troy D; Rodrigues, Richard R; Williams, Mark A

    2016-01-01

    Honey bees (Apis mellifera) are the primary pollinators of major horticultural crops. Over the last few decades, a substantial decline in honey bees and their colonies have been reported. While a plethora of factors could contribute to the putative decline, pathogens, and pesticides are common concerns that draw attention. In addition to potential direct effects on honey bees, indirect pesticide effects could include alteration of essential gut microbial communities and symbionts that are important to honey bee health (e.g., immune system). The primary objective of this study was to determine the microbiome associated with honey bees exposed to commonly used in-hive pesticides: coumaphos, tau-fluvalinate, and chlorothalonil. Treatments were replicated at three independent locations near Blacksburg Virginia, and included a no-pesticide amended control at each location. The microbiome was characterized through pyrosequencing of V2-V3 regions of the bacterial 16S rRNA gene and fungal ITS region. Pesticide exposure significantly affected the structure of bacterial but not fungal communities. The bee bacteriome, similar to other studies, was dominated by sequences derived from Bacilli, Actinobacteria, α-, β-, γ-proteobacteria. The fungal community sequences were dominated by Ascomycetes and Basidiomycetes. The Multi-response permutation procedures (MRPP) and subsequent Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) analysis indicated that chlorothalonil caused significant change to the structure and functional potential of the honey bee gut bacterial community relative to control. Putative genes for oxidative phosphorylation, for example, increased while sugar metabolism and peptidase potential declined in the microbiome of chlorothalonil exposed bees. The results of this field-based study suggest the potential for pesticide induced changes to the honey bee gut microbiome that warrant further investigation.

  18. Lateral gene transfer of an ABC transporter complex between major constituents of the human gut microbiome

    Directory of Open Access Journals (Sweden)

    Meehan Conor J

    2012-11-01

    Full Text Available Abstract Background Several links have been established between the human gut microbiome and conditions such as obesity and inflammatory bowel syndrome. This highlights the importance of understanding what properties of the gut microbiome can affect the health of the human host. Studies have been undertaken to determine the species composition of this microbiome and infer functional profiles associated with such host properties. However, lateral gene transfer (LGT between community members may result in misleading taxonomic attributions for the recipient organisms, thus making species-function links difficult to establish. Results We identified a peptides/nickel transport complex whose components differed in abundance based upon levels of host obesity, and assigned the encoded proteins to members of the microbial community. Each protein was assigned to several distinct taxonomic groups, with moderate levels of agreement observed among different proteins in the complex. Phylogenetic trees of these proteins produced clusters that differed greatly from taxonomic attributions and indicated that habitat-directed LGT of this complex is likely to have occurred, though not always between the same partners. Conclusions These findings demonstrate that certain membrane transport systems may be an important factor within an obese-associated gut microbiome and that such complexes may be acquired several times by different strains of the same species. Additionally, an example of individual proteins from different organisms being transferred into one operon was observed, potentially demonstrating a functional complex despite the donors of the subunits being taxonomically disparate. Our results also highlight the potential impact of habitat-directed LGT on the resident microbiota.

  19. Influence of early life exposure, host genetics and diet on the mouse gut microbiome and metabolome

    Energy Technology Data Exchange (ETDEWEB)

    Snijders, Antoine M.; Langley, Sasha A.; Kim, Young-Mo; Brislawn, Colin J.; Noecker, Cecilia; Zink, Erika M.; Fansler, Sarah J.; Casey, Cameron P.; Miller, Darla R.; Huang, Yurong; Karpen, Gary H.; Celniker, Susan E.; Brown, James B.; Borenstein, Elhanan; Jansson, Janet K.; Metz, Thomas O.; Mao, Jian-Hua

    2016-11-28

    Although the gut microbiome plays important roles in host physiology, health and disease1, we lack understanding of the complex interplay between host genetics and early life environment on the microbial and metabolic composition of the gut.We used the genetically diverse Collaborative Cross mouse system2 to discover that early life history impacts themicrobiome composition, whereas dietary changes have only a moderate effect. By contrast, the gut metabolome was shaped mostly by diet, with specific non-dietary metabolites explained by microbial metabolism. Quantitative trait analysis identified mouse genetic trait loci (QTL) that impact the abundances of specific microbes. Human orthologues of genes in the mouse QTL are implicated in gastrointestinal cancer. Additionally, genes located in mouse QTL for Lactobacillales abundance are implicated in arthritis, rheumatic disease and diabetes. Furthermore, Lactobacillales abundance was predictive of higher host T-helper cell counts, suggesting an important link between Lactobacillales and host adaptive immunity.

  20. An obesity-associated gut microbiome reprograms the intestinal epigenome and leads to altered colonic gene expression.

    Science.gov (United States)

    Qin, Yufeng; Roberts, John D; Grimm, Sara A; Lih, Fred B; Deterding, Leesa J; Li, Ruifang; Chrysovergis, Kaliopi; Wade, Paul A

    2018-01-23

    The gut microbiome, a key constituent of the colonic environment, has been implicated as an important modulator of human health. The eukaryotic epigenome is postulated to respond to environmental stimuli through alterations in chromatin features and, ultimately, gene expression. How the host mediates epigenomic responses to gut microbiota is an emerging area of interest. Here, we profile the gut microbiome and chromatin characteristics in colon epithelium from mice fed either an obesogenic or control diet, followed by an analysis of the resultant changes in gene expression. The obesogenic diet shapes the microbiome prior to the development of obesity, leading to altered bacterial metabolite production which predisposes the host to obesity. This microbiota-diet interaction leads to changes in histone modification at active enhancers that are enriched for binding sites for signal responsive transcription factors. These alterations of histone methylation and acetylation are associated with signaling pathways integral to the development of colon cancer. The transplantation of obesogenic diet-conditioned microbiota into germ free mice, combined with an obesogenic diet, recapitulates the features of the long-term diet regimen. The diet/microbiome-dependent changes are reflected in both the composition of the recipient animals' microbiome as well as in the set of transcription factor motifs identified at diet-influenced enhancers. These findings suggest that the gut microbiome, under specific dietary exposures, stimulates a reprogramming of the enhancer landscape in the colon, with downstream effects on transcription factors. These chromatin changes may be associated with those seen during colon cancer development.

  1. Moderate-Intensity Exercise Affects Gut Microbiome Composition and Influences Cardiac Function in Myocardial Infarction Mice

    Directory of Open Access Journals (Sweden)

    Zuheng Liu

    2017-09-01

    Full Text Available Physical exercise is commonly regarded as protective against cardiovascular disease (CVD. Recent studies have reported that exercise alters the gut microbiota and that modification of the gut microbiota can influence cardiac function. Here, we focused on the relationships among exercise, the gut microbiota and cardiac function after myocardial infarction (MI. Four-week-old C57BL/6J mice were exercised on a treadmill for 4 weeks before undergoing left coronary artery ligation. Cardiac function was assessed using echocardiography. Gut microbiomes were evaluated post-exercise and post-MI using 16S rRNA gene sequencing on an Illumina HiSeq platform. Exercise training inhibited declines in cardiac output and stroke volume in post-MI mice. In addition, physical exercise and MI led to alterations in gut microbial composition. Exercise training increased the relative abundance of Butyricimonas and Akkermansia. Additionally, key operational taxonomic units were identified, including 24 lineages (mainly from Bacteroidetes, Barnesiella, Helicobacter, Parabacteroides, Porphyromonadaceae, Ruminococcaceae, and Ureaplasma that were closely related to exercise and cardiac function. These results suggested that exercise training improved cardiac function to some extent in addition to altering the gut microbiota; therefore, they could provide new insights into the use of exercise training for the treatment of CVD.

  2. Construction and Analysis of Functional Networks in the Gut Microbiome of Type 2 Diabetes Patients.

    Science.gov (United States)

    Li, Lianshuo; Wang, Zicheng; He, Peng; Ma, Shining; Du, Jie; Jiang, Rui

    2016-10-01

    Although networks of microbial species have been widely used in the analysis of 16S rRNA sequencing data of a microbiome, the construction and analysis of a complete microbial gene network are in general problematic because of the large number of microbial genes in metagenomics studies. To overcome this limitation, we propose to map microbial genes to functional units, including KEGG orthologous groups and the evolutionary genealogy of genes: Non-supervised Orthologous Groups (eggNOG) orthologous groups, to enable the construction and analysis of a microbial functional network. We devised two statistical methods to infer pairwise relationships between microbial functional units based on a deep sequencing dataset of gut microbiome from type 2 diabetes (T2D) patients as well as healthy controls. Networks containing such functional units and their significant interactions were constructed subsequently. We conducted a variety of analyses of global properties, local properties, and functional modules in the resulting functional networks. Our data indicate that besides the observations consistent with the current knowledge, this study provides novel biological insights into the gut microbiome associated with T2D. Copyright © 2016. Production and hosting by Elsevier Ltd.

  3. Microbiota in allergy and asthma and the emerging relationship with the gut microbiome.

    Science.gov (United States)

    Fujimura, Kei E; Lynch, Susan V

    2015-05-13

    Asthma and atopy, classically associated with hyper-activation of the T helper 2 (Th2) arm of adaptive immunity, are among the most common chronic illnesses worldwide. Emerging evidence relates atopy and asthma to the composition and function of the human microbiome, the collection of microbes that reside in and on and interact with the human body. The ability to interrogate microbial ecology of the human host is due in large part to recent technological developments that permit identification of microbes and their products using culture-independent molecular detection techniques. In this review we explore the roles of respiratory, gut, and environmental microbiomes in asthma and allergic disease development, manifestation, and attenuation. Though still a relatively nascent field of research, evidence to date suggests that the airway and/or gut microbiome may represent fertile targets for prevention or management of allergic asthma and other diseases in which adaptive immune dysfunction is a prominent feature. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Intestinal microbiome-gut-brain axis and irritable bowel syndrome.

    Science.gov (United States)

    Moser, Gabriele; Fournier, Camille; Peter, Johannes

    2018-03-01

    Psychological comorbidity is highly present in irritable bowel syndrome (IBS). Recent research points to a role of intestinal microbiota in visceral hypersensitivity, anxiety, and depression. Increased disease reactivity to psychological stress has been described too. A few clinical studies have attempted to identify features of dysbiosis in IBS. While animal studies revealed strong associations between stress and gut microbiota, studies in humans are rare. This review covers the most important studies on intestinal microbial correlates of psychological and clinical features in IBS, including stress, anxiety, and depression.

  5. Gut microbiome may contribute to insulin resistance and systemic inflammation in obese rodents: a meta-analysis.

    Science.gov (United States)

    Jiao, Na; Baker, Susan S; Nugent, Colleen A; Tsompana, Maria; Cai, Liting; Wang, Yong; Buck, Michael J; Genco, Robert J; Baker, Robert D; Zhu, Ruixin; Zhu, Lixin

    2018-04-01

    A number of studies have associated obesity with altered gut microbiota, although results are discordant regarding compositional changes in the gut microbiota of obese animals. Herein we used a meta-analysis to obtain an unbiased evaluation of structural and functional changes of the gut microbiota in diet-induced obese rodents. The raw sequencing data of nine studies generated from high-fat diet (HFD)-induced obese rodent models were processed with QIIME to obtain gut microbiota compositions. Biological functions were predicted and annotated with KEGG pathways with PICRUSt. No significant difference was observed for alpha diversity and Bacteroidetes-to-Firmicutes ratio between obese and lean rodents. Bacteroidia, Clostridia, Bacilli, and Erysipelotrichi were dominant classes, but gut microbiota compositions varied among studies. Meta-analysis of the nine microbiome data sets identified 15 differential taxa and 57 differential pathways between obese and lean rodents. In obese rodents, increased abundance was observed for Dorea, Oscillospira, and Ruminococcus, known for fermenting polysaccharide into short chain fatty acids (SCFAs). Decreased Turicibacter and increased Lactococcus are consistent with elevated inflammation in the obese status. Differential functional pathways of the gut microbiome in obese rodents included enriched pyruvate metabolism, butanoate metabolism, propanoate metabolism, pentose phosphate pathway, fatty acid biosynthesis, and glycerolipid metabolism pathways. These pathways converge in the function of carbohydrate metabolism, SCFA metabolism, and biosynthesis of lipid. HFD-induced obesity results in structural and functional dysbiosis of gut microbiota. The altered gut microbiome may contribute to obesity development by promoting insulin resistance and systemic inflammation.

  6. Gut microbiome response to short-term dietary interventions in reactive hypoglycemia subjects.

    Science.gov (United States)

    Quercia, Sara; Turroni, Silvia; Fiori, Jessica; Soverini, Matteo; Rampelli, Simone; Biagi, Elena; Castagnetti, Andrea; Consolandi, Clarissa; Severgnini, Marco; Pianesi, Mario; Fallucca, Francesco; Pozzilli, Paolo; Brigidi, Patrizia; Candela, Marco

    2017-11-01

    Reactive hypoglycemia is a metabolic disorder that provokes severe hypoglycemic episodes after meals. Over recent years, the gut microbiota has been recognized as potential target for the control of metabolic diseases, and the possibility to correct gut microbiota dysbioses through diet, favouring the recovery of metabolic homeostasis, has been considered. We investigate the impact of 2 short-term (3-day) nutritional interventions, based on the macrobiotic Ma-Pi 2 diet and a control Mediterranean diet, on the structure and functionality of the gut microbiota in 12 patients affected by reactive hypoglycemia. The gut microbiota composition was characterized by next-generation sequencing of the V3 to V4 region of the 16S rRNA gene, and the ecosystem functionality was addressed by measuring the faecal concentration of short-chain fatty acids (SCFAs). In order to measure the short-term physiological gut microbiota fluctuation, the microbiomes of 7 healthy people were characterized before and after 3 days of constant diet. While no convergence of the gut microbiota compositional profiles was observed, a significant increase in SCFA faecal levels was induced only in the Ma-Pi 2 diet group, suggesting the potential of this diet to support a short-term functional convergence of the gut microbiota, regardless of the individual compositional layout. The Ma-Pi 2 diet, with its high fibre load, was effective in increasing the production of SCFAs by the gut microbiota. Because these metabolites are known for their ability to counterbalance the metabolic deregulation in persons with glucose impairment disorders, their increased bioavailability could be of some relevance in reactive hypoglycemia. Copyright © 2017 John Wiley & Sons, Ltd.

  7. Metabolic Modeling of Common Escherichia coli Strains in Human Gut Microbiome

    Directory of Open Access Journals (Sweden)

    Yue-Dong Gao

    2014-01-01

    Full Text Available The recent high-throughput sequencing has enabled the composition of Escherichia coli strains in the human microbial community to be profiled en masse. However, there are two challenges to address: (1 exploring the genetic differences between E. coli strains in human gut and (2 dynamic responses of E. coli to diverse stress conditions. As a result, we investigated the E. coli strains in human gut microbiome using deep sequencing data and reconstructed genome-wide metabolic networks for the three most common E. coli strains, including E. coli HS, UTI89, and CFT073. The metabolic models show obvious strain-specific characteristics, both in network contents and in behaviors. We predicted optimal biomass production for three models on four different carbon sources (acetate, ethanol, glucose, and succinate and found that these stress-associated genes were involved in host-microbial interactions and increased in human obesity. Besides, it shows that the growth rates are similar among the models, but the flux distributions are different, even in E. coli core reactions. The correlations between human diabetes-associated metabolic reactions in the E. coli models were also predicted. The study provides a systems perspective on E. coli strains in human gut microbiome and will be helpful in integrating diverse data sources in the following study.

  8. Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling.

    Science.gov (United States)

    Severance, Emily G; Yolken, Robert H; Eaton, William W

    2016-09-01

    Autoimmunity, gastrointestinal (GI) disorders and schizophrenia have been associated with one another for a long time. This paper reviews these connections and provides a context by which multiple risk factors for schizophrenia may be related. Epidemiological studies strongly link schizophrenia with autoimmune disorders including enteropathic celiac disease. Exposure to wheat gluten and bovine milk casein also contribute to non-celiac food sensitivities in susceptible individuals. Co-morbid GI inflammation accompanies humoral immunity to food antigens, occurs early during the course of schizophrenia and appears to be independent from antipsychotic-generated motility effects. This inflammation impacts endothelial barrier permeability and can precipitate translocation of gut bacteria into systemic circulation. Infection by the neurotropic gut pathogen, Toxoplasma gondii, will elicit an inflammatory GI environment. Such processes trigger innate immunity, including activation of complement C1q, which also functions at synapses in the brain. The emerging field of microbiome research lies at the center of these interactions with evidence that the abundance and diversity of resident gut microbiota contribute to digestion, inflammation, gut permeability and behavior. Dietary modifications of core bacterial compositions may explain inefficient gluten digestion and how immigrant status in certain situations is a risk factor for schizophrenia. Gut microbiome research in schizophrenia is in its infancy, but data in related fields suggest disease-associated altered phylogenetic compositions. In summary, this review surveys associative and experimental data linking autoimmunity, GI activity and schizophrenia, and proposes that understanding of disrupted biological pathways outside of the brain can lend valuable information regarding pathogeneses of complex, polygenic brain disorders. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Gut Microbiota and a Selectively Bred Taste Phenotype: A Novel Model of Microbiome-Behavior Relationships.

    Science.gov (United States)

    Lyte, Mark; Fodor, Anthony A; Chapman, Clinton D; Martin, Gary G; Perez-Chanona, Ernesto; Jobin, Christian; Dess, Nancy K

    2016-06-01

    The microbiota-gut-brain axis is increasingly implicated in obesity, anxiety, stress, and other health-related processes. Researchers have proposed that gut microbiota may influence dietary habits, and pathways through the microbiota-gut-brain axis make such a relationship feasible; however, few data bear on the hypothesis. As a first step in the development of a model system, the gut microbiome was examined in rat lines selectively outbred on a taste phenotype with biobehavioral profiles that have diverged with respect to energy regulation, anxiety, and stress. Occidental low and high-saccharin-consuming rats were assessed for body mass and chow, water, and saccharin intake; littermate controls had shared cages with rats in the experimental group but were not assessed. Cecum and colon microbial communities were profiled using Illumina 16S rRNA sequencing and multivariate analysis of microbial diversity and composition. The saccharin phenotype was confirmed (low-saccharin-consuming rats, 0.7Δ% [0.9Δ%]; high-saccharin-consuming rats, 28.1Δ% [3.6Δ%]). Regardless of saccharin exposure, gut microbiota differed between lines in terms of overall community similarity and taxa at lower phylogenetic levels. Specifically, 16 genera in three phyla distinguished the lines at a 10% false discovery rate. The study demonstrates for the first time that rodent lines created through selective pressure on taste and differing on functionally related correlates host different microbial communities. Whether the microbiota are causally related to the taste phenotype or its correlates remains to be determined. These findings encourage further inquiry on the relationship of the microbiome to taste, dietary habits, emotion, and health.

  10. Heterogeneity of the gut microbiome in mice: guidelines for optimizing experimental design

    Science.gov (United States)

    Laukens, Debby; Brinkman, Brigitta M.; Raes, Jeroen; De Vos, Martine; Vandenabeele, Peter

    2015-01-01

    Targeted manipulation of the gut flora is increasingly being recognized as a means to improve human health. Yet, the temporal dynamics and intra- and interindividual heterogeneity of the microbiome represent experimental limitations, especially in human cross-sectional studies. Therefore, rodent models represent an invaluable tool to study the host–microbiota interface. Progress in technical and computational tools to investigate the composition and function of the microbiome has opened a new era of research and we gradually begin to understand the parameters that influence variation of host-associated microbial communities. To isolate true effects from confounding factors, it is essential to include such parameters in model intervention studies. Also, explicit journal instructions to include essential information on animal experiments are mandatory. The purpose of this review is to summarize the factors that influence microbiota composition in mice and to provide guidelines to improve the reproducibility of animal experiments. PMID:26323480

  11. Bacteria of the human gut microbiome catabolize red seaweed glycans with carbohydrate-active enzyme updates from extrinsic microbes

    OpenAIRE

    Hehemann, Jan-Hendrik; Kelly, Amelia G.; Pudlo, Nicholas A.; Martens, Eric C.; Boraston, Alisdair B.

    2012-01-01

    Humans host an intestinal population of microbes—collectively referred to as the gut microbiome—which encode the carbohydrate active enzymes, or CAZymes, that are absent from the human genome. These CAZymes help to extract energy from recalcitrant polysaccharides. The question then arises as to if and how the microbiome adapts to new carbohydrate sources when modern humans change eating habits. Recent metagenome analysis of microbiomes from healthy American, Japanese, and Spanish populations ...

  12. Understanding the gut microbiome of dairy calves: Opportunities to improve early-life gut health.

    Science.gov (United States)

    Malmuthuge, Nilusha; Guan, Le Luo

    2017-07-01

    Early gut microbiota plays a vital role in the long-term health of the host. However, understanding of these microbiota is very limited in livestock species, especially in dairy calves. Neonatal calves are highly susceptible to enteric infections, one of the major causes of calf death, so approaches to improving gut health and overall calf health are needed. An increasing number of studies are exploring the microbial composition of the gut, the mucosal immune system, and early dietary interventions to improve the health of dairy calves, revealing possibilities for effectively reducing the susceptibility of calves to enteric infections while promoting growth. Still, comprehensive understanding of the effect of dietary interventions on gut microbiota-one of the key aspects of gut health-is lacking. Such knowledge may provide in-depth understanding of the mechanisms behind functional changes in response to dietary interventions. Understanding of host-microbial interactions with dietary interventions and the role of the gut microbiota during pathogenesis at the site of infection in early life is vital for designing effective tools and techniques to improve calf gut health. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  13. Mucin glycan foraging in the human gut microbiome

    Science.gov (United States)

    Tailford, Louise E.; Crost, Emmanuelle H.; Kavanaugh, Devon; Juge, Nathalie

    2015-01-01

    The availability of host and dietary carbohydrates in the gastrointestinal (GI) tract plays a key role in shaping the structure-function of the microbiota. In particular, some gut bacteria have the ability to forage on glycans provided by the mucus layer covering the GI tract. The O-glycan structures present in mucin are diverse and complex, consisting predominantly of core 1-4 mucin-type O-glycans containing α- and β- linked N-acetyl-galactosamine, galactose and N-acetyl-glucosamine. These core structures are further elongated and frequently modified by fucose and sialic acid sugar residues via α1,2/3/4 and α2,3/6 linkages, respectively. The ability to metabolize these mucin O-linked oligosaccharides is likely to be a key factor in determining which bacterial species colonize the mucosal surface. Due to their proximity to the immune system, mucin-degrading bacteria are in a prime location to influence the host response. However, despite the growing number of bacterial genome sequences available from mucin degraders, our knowledge on the structural requirements for mucin degradation by gut bacteria remains fragmented. This is largely due to the limited number of functionally characterized enzymes and the lack of studies correlating the specificity of these enzymes with the ability of the strain to degrade and utilize mucin and mucin glycans. This review focuses on recent findings unraveling the molecular strategies used by mucin-degrading bacteria to utilize host glycans, adapt to the mucosal environment, and influence human health. PMID:25852737

  14. Identifying keystone species in the human gut microbiome from metagenomic timeseries using sparse linear regression.

    Directory of Open Access Journals (Sweden)

    Charles K Fisher

    Full Text Available Human associated microbial communities exert tremendous influence over human health and disease. With modern metagenomic sequencing methods it is now possible to follow the relative abundance of microbes in a community over time. These microbial communities exhibit rich ecological dynamics and an important goal of microbial ecology is to infer the ecological interactions between species directly from sequence data. Any algorithm for inferring ecological interactions must overcome three major obstacles: 1 a correlation between the abundances of two species does not imply that those species are interacting, 2 the sum constraint on the relative abundances obtained from metagenomic studies makes it difficult to infer the parameters in timeseries models, and 3 errors due to experimental uncertainty, or mis-assignment of sequencing reads into operational taxonomic units, bias inferences of species interactions due to a statistical problem called "errors-in-variables". Here we introduce an approach, Learning Interactions from MIcrobial Time Series (LIMITS, that overcomes these obstacles. LIMITS uses sparse linear regression with boostrap aggregation to infer a discrete-time Lotka-Volterra model for microbial dynamics. We tested LIMITS on synthetic data and showed that it could reliably infer the topology of the inter-species ecological interactions. We then used LIMITS to characterize the species interactions in the gut microbiomes of two individuals and found that the interaction networks varied significantly between individuals. Furthermore, we found that the interaction networks of the two individuals are dominated by distinct "keystone species", Bacteroides fragilis and Bacteroided stercosis, that have a disproportionate influence on the structure of the gut microbiome even though they are only found in moderate abundance. Based on our results, we hypothesize that the abundances of certain keystone species may be responsible for individuality in

  15. New frontiers in nanotoxicology: Gut microbiota/microbiome-mediated effects of engineered nanomaterials.

    Science.gov (United States)

    Pietroiusti, Antonio; Magrini, Andrea; Campagnolo, Luisa

    2016-05-15

    It has been recently recognized that the gut microbiota, the community of organisms living within the gastrointestinal tract is an integral part of the human body, and that its genoma (the microbiome) interacts with the genes expressed by the cells of the host organism. Several important physiological functions require the cooperation of microbiota/microbiome, whose alterations play an important role in several human diseases. On this basis, it is probable that microbiota/microbiome may in part be involved in many biological effects of engineered nanomaterials (ENMs). There are still few reports on the possible toxicological effects of ENMs on microbiota/microbiome, and on their possible clinical consequences. Available data suggest that several ENMs, including carbon nanotubes (CNTs), titanium dioxide, cerium dioxide, zinc oxide, nanosilica and nanosilver may affect the microbiota and that clinical disorders such as colitis, obesity and immunological dysfunctions might follow. On the other hand, other ENMs such as iron nanoparticles may show advantages over traditional iron-based supplemental treatment because they do not interfere with the microbiota/microbiome, and some ENM-based therapeutic interventions might be employed for treating intestinal infections, while sparing the microbiota. The final section of the review is focused on the possible future developments of the research in this field: new in vitro and in vivo models, possible biomarkers and new pathophysiological pathways are proposed and discussed, as well as the possibility that metabolic changes following ENMs/microbiota interactions might be exploited as a fingerprint of ENM exposure. The potential toxicological relevance of physico-chemical modifications of ENMs induced by the microbiota is also highlighted. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. New frontiers in nanotoxicology: Gut microbiota/microbiome-mediated effects of engineered nanomaterials

    International Nuclear Information System (INIS)

    Pietroiusti, Antonio; Magrini, Andrea; Campagnolo, Luisa

    2016-01-01

    It has been recently recognized that the gut microbiota, the community of organisms living within the gastrointestinal tract is an integral part of the human body, and that its genoma (the microbiome) interacts with the genes expressed by the cells of the host organism. Several important physiological functions require the cooperation of microbiota/microbiome, whose alterations play an important role in several human diseases. On this basis, it is probable that microbiota/microbiome may in part be involved in many biological effects of engineered nanomaterials (ENMs). There are still few reports on the possible toxicological effects of ENMs on microbiota/microbiome, and on their possible clinical consequences. Available data suggest that several ENMs, including carbon nanotubes (CNTs), titanium dioxide, cerium dioxide, zinc oxide, nanosilica and nanosilver may affect the microbiota and that clinical disorders such as colitis, obesity and immunological dysfunctions might follow. On the other hand, other ENMs such as iron nanoparticles may show advantages over traditional iron-based supplemental treatment because they do not interfere with the microbiota/microbiome, and some ENM-based therapeutic interventions might be employed for treating intestinal infections, while sparing the microbiota. The final section of the review is focused on the possible future developments of the research in this field: new in vitro and in vivo models, possible biomarkers and new pathophysiological pathways are proposed and discussed, as well as the possibility that metabolic changes following ENMs/microbiota interactions might be exploited as a fingerprint of ENM exposure. The potential toxicological relevance of physico-chemical modifications of ENMs induced by the microbiota is also highlighted. - Highlights: • Interactions between ENMs and microbiota are largely unexplored. • Microbiota probably mediates several ENMs' biological actions. • ENMs/microbiota interactions

  17. New frontiers in nanotoxicology: Gut microbiota/microbiome-mediated effects of engineered nanomaterials

    Energy Technology Data Exchange (ETDEWEB)

    Pietroiusti, Antonio, E-mail: pietroiu@uniroma2.it; Magrini, Andrea; Campagnolo, Luisa

    2016-05-15

    It has been recently recognized that the gut microbiota, the community of organisms living within the gastrointestinal tract is an integral part of the human body, and that its genoma (the microbiome) interacts with the genes expressed by the cells of the host organism. Several important physiological functions require the cooperation of microbiota/microbiome, whose alterations play an important role in several human diseases. On this basis, it is probable that microbiota/microbiome may in part be involved in many biological effects of engineered nanomaterials (ENMs). There are still few reports on the possible toxicological effects of ENMs on microbiota/microbiome, and on their possible clinical consequences. Available data suggest that several ENMs, including carbon nanotubes (CNTs), titanium dioxide, cerium dioxide, zinc oxide, nanosilica and nanosilver may affect the microbiota and that clinical disorders such as colitis, obesity and immunological dysfunctions might follow. On the other hand, other ENMs such as iron nanoparticles may show advantages over traditional iron-based supplemental treatment because they do not interfere with the microbiota/microbiome, and some ENM-based therapeutic interventions might be employed for treating intestinal infections, while sparing the microbiota. The final section of the review is focused on the possible future developments of the research in this field: new in vitro and in vivo models, possible biomarkers and new pathophysiological pathways are proposed and discussed, as well as the possibility that metabolic changes following ENMs/microbiota interactions might be exploited as a fingerprint of ENM exposure. The potential toxicological relevance of physico-chemical modifications of ENMs induced by the microbiota is also highlighted. - Highlights: • Interactions between ENMs and microbiota are largely unexplored. • Microbiota probably mediates several ENMs' biological actions. • ENMs/microbiota interactions

  18. The Core Gut Microbiome of the American Cockroach, Periplaneta americana, Is Stable and Resilient to Dietary Shifts.

    Science.gov (United States)

    Tinker, Kara A; Ottesen, Elizabeth A

    2016-11-15

    The omnivorous cockroach Periplaneta americana hosts a diverse hindgut microbiota encompassing hundreds of microbial species. In this study, we used 16S rRNA gene sequencing to examine the effect of diet on the composition of the P. americana hindgut microbial community. Results show that the hindgut microbiota of P. americana exhibit a highly stable core microbial community with low variance in compositions between individuals and minimal community change in response to dietary shifts. This core hindgut microbiome is shared between laboratory-hosted and wild-caught individuals, although wild-caught specimens exhibited a higher diversity of low-abundance microbes that were lost following extended cultivation under laboratory conditions. This taxonomic stability strongly contrasts with observations of the gut microbiota of mammals, which have been shown to be highly responsive to dietary change. A comparison of P. americana hindgut samples with human fecal samples indicated that the cockroach hindgut community exhibited higher alpha diversity but a substantially lower beta diversity than the human gut microbiome. This suggests that cockroaches have evolved unique mechanisms for establishing and maintaining a diverse and stable core microbiome. The gut microbiome plays an important role in the overall health of its host. A healthy gut microbiota typically assists with defense against pathogens and the digestion and absorption of nutrients from food, while dysbiosis of the gut microbiota has been associated with reduced health. In this study, we examined the composition and stability of the gut microbiota from the omnivorous cockroach Periplaneta americana. We found that P. americana hosts a diverse core gut microbiome that remains stable after drastic long-term changes in diet. While other insects, notably ant and bee species, have evolved mechanisms for maintaining a stable association with specific gut microbiota, these insects typically host low-diversity gut

  19. Machine Learning Leveraging Genomes from Metagenomes Identifies Influential Antibiotic Resistance Genes in the Infant Gut Microbiome

    Science.gov (United States)

    Olm, Matthew R.; Morowitz, Michael J.

    2018-01-01

    ABSTRACT Antibiotic resistance in pathogens is extensively studied, and yet little is known about how antibiotic resistance genes of typical gut bacteria influence microbiome dynamics. Here, we leveraged genomes from metagenomes to investigate how genes of the premature infant gut resistome correspond to the ability of bacteria to survive under certain environmental and clinical conditions. We found that formula feeding impacts the resistome. Random forest models corroborated by statistical tests revealed that the gut resistome of formula-fed infants is enriched in class D beta-lactamase genes. Interestingly, Clostridium difficile strains harboring this gene are at higher abundance in formula-fed infants than C. difficile strains lacking this gene. Organisms with genes for major facilitator superfamily drug efflux pumps have higher replication rates under all conditions, even in the absence of antibiotic therapy. Using a machine learning approach, we identified genes that are predictive of an organism’s direction of change in relative abundance after administration of vancomycin and cephalosporin antibiotics. The most accurate results were obtained by reducing annotated genomic data to five principal components classified by boosted decision trees. Among the genes involved in predicting whether an organism increased in relative abundance after treatment are those that encode subclass B2 beta-lactamases and transcriptional regulators of vancomycin resistance. This demonstrates that machine learning applied to genome-resolved metagenomics data can identify key genes for survival after antibiotics treatment and predict how organisms in the gut microbiome will respond to antibiotic administration. IMPORTANCE The process of reconstructing genomes from environmental sequence data (genome-resolved metagenomics) allows unique insight into microbial systems. We apply this technique to investigate how the antibiotic resistance genes of bacteria affect their ability to

  20. Antibiotic-induced shifts in the mouse gut microbiome and metabolome increase susceptibility to Clostridium difficile infection

    Science.gov (United States)

    Theriot, Casey M.; Koenigsknecht, Mark J.; Carlson, Paul E.; Hatton, Gabrielle E.; Nelson, Adam M.; Li, Bo; Huffnagle, Gary B.; Li, Jun; Young, Vincent B.

    2014-01-01

    Antibiotics can have significant and long lasting effects on the gastrointestinal tract microbiota, reducing colonization resistance against pathogens including Clostridium difficile. Here we show that antibiotic treatment induces substantial changes in the gut microbial community and in the metabolome of mice susceptible to C. difficile infection. Levels of secondary bile acids, glucose, free fatty acids, and dipeptides decrease, whereas those of primary bile acids and sugar alcohols increase, reflecting the modified metabolic activity of the altered gut microbiome. In vitro and ex vivo analyses demonstrate that C. difficile can exploit specific metabolites that become more abundant in the mouse gut after antibiotics, including primary bile acid taurocholate for germination, and carbon sources mannitol, fructose, sorbitol, raffinose and stachyose for growth. Our results indicate that antibiotic-mediated alteration of the gut microbiome converts the global metabolic profile to one that favors C. difficile germination and growth. PMID:24445449

  1. Recovery of the gut microbiome following fecal microbiota transplantation.

    Science.gov (United States)

    Seekatz, Anna M; Aas, Johannes; Gessert, Charles E; Rubin, Timothy A; Saman, Daniel M; Bakken, Johan S; Young, Vincent B

    2014-06-17

    Clostridium difficile infection is one of the most common health care-associated infections, and up to 40% of patients suffer from recurrence of disease following standard antibiotic therapy. Recently, fecal microbiota transplantation (FMT) has been successfully used to treat recurrent C. difficile infection. It is hypothesized that FMT aids in recovery of a microbiota capable of colonization resistance to C. difficile. However, it is not fully understood how this occurs. Here we investigated changes in the fecal microbiota structure following FMT in patients with recurrent C. difficile infection, and imputed a hypothetical functional profile based on the 16S rRNA profile using a predictive metagenomic tool. Increased relative abundance of Bacteroidetes and decreased abundance of Proteobacteria were observed following FMT. The fecal microbiota of recipients following transplantation was more diverse and more similar to the donor profile than the microbiota prior to transplantation. Additionally, we observed differences in the imputed metagenomic profile. In particular, amino acid transport systems were overrepresented in samples collected prior to transplantation. These results suggest that functional changes accompany microbial structural changes following this therapy. Further identification of the specific community members and functions that promote colonization resistance may aid in the development of improved treatment methods for C. difficile infection. Within the last decade, Clostridium difficile infection has surpassed other bacterial infections to become the leading cause of nosocomial infections. Antibiotic use, which disrupts the gut microbiota and its capability in providing colonization resistance against C. difficile, is a known risk factor in C. difficile infection. In particular, recurrent C. difficile remains difficult to treat with standard antibiotic therapy. Fecal microbiota transplantation (FMT) has provided a successful treatment method for

  2. Altered Gut Microbiome Composition and Tryptic Activity of the 5xFAD Alzheimer's Mouse Model.

    Science.gov (United States)

    Brandscheid, Carolin; Schuck, Florian; Reinhardt, Sven; Schäfer, Karl-Herbert; Pietrzik, Claus U; Grimm, Marcus; Hartmann, Tobias; Schwiertz, Andreas; Endres, Kristina

    2017-01-01

    The regulation of physiological gut functions such as peristalsis or secretion of digestive enzymes by the central nervous system via the Nervus vagus is well known. Recent investigations highlight that pathological conditions of neurological or psychiatric disorders might directly interfere with the autonomous neuronal network of the gut - the enteric nervous system, or even derive from there. By using a murine Alzheimer's disease model, we investigated a potential influence of disease-associated changes on gastrointestinal properties. 5xFAD mice at three different ages were compared to wild type littermates in regard to metabolic parameters and enzymes of the gut by fluorimetric enzyme assay and western blotting. Overexpression of human amyloid-β protein precursor (AβPP) within the gut was assessed by qPCR and IHC; fecal microbiome analysis was conducted by 16SrRNA quantitation of selected phyla and species. While general composition of fecal samples, locomotion, and food consumption of male 5xFAD animals were not changed, we observed a reduced body weight occurring at early pathological stages. Human AβPP was not only expressed within the brain of these mice but also in gut tissue. Analysis of fecal proteins revealed a reduced trypsin amount in the 5xFAD model mice as compared to the wild type. In addition, we observed changes in fecal microbiota composition along with age. We therefore suggest that the presence of the mutated transgenes (AβPP and PS1), which are per se the basis for the genetic form of Alzheimer's disease in humans, directly interferes with gut function as shown here for the disease model mice.

  3. Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition.

    Science.gov (United States)

    Wong, M-L; Inserra, A; Lewis, M D; Mastronardi, C A; Leong, L; Choo, J; Kentish, S; Xie, P; Morrison, M; Wesselingh, S L; Rogers, G B; Licinio, J

    2016-06-01

    The inflammasome is hypothesized to be a key mediator of the response to physiological and psychological stressors, and its dysregulation may be implicated in major depressive disorder. Inflammasome activation causes the maturation of caspase-1 and activation of interleukin (IL)-1β and IL-18, two proinflammatory cytokines involved in neuroimmunomodulation, neuroinflammation and neurodegeneration. In this study, C57BL/6 mice with genetic deficiency or pharmacological inhibition of caspase-1 were screened for anxiety- and depressive-like behaviors, and locomotion at baseline and after chronic stress. We found that genetic deficiency of caspase-1 decreased depressive- and anxiety-like behaviors, and conversely increased locomotor activity and skills. Caspase-1 deficiency also prevented the exacerbation of depressive-like behaviors following chronic stress. Furthermore, pharmacological caspase-1 antagonism with minocycline ameliorated stress-induced depressive-like behavior in wild-type mice. Interestingly, chronic stress or pharmacological inhibition of caspase-1 per se altered the fecal microbiome in a very similar manner. When stressed mice were treated with minocycline, the observed gut microbiota changes included increase in relative abundance of Akkermansia spp. and Blautia spp., which are compatible with beneficial effects of attenuated inflammation and rebalance of gut microbiota, respectively, and the increment in Lachnospiracea abundance was consistent with microbiota changes of caspase-1 deficiency. Our results suggest that the protective effect of caspase-1 inhibition involves the modulation of the relationship between stress and gut microbiota composition, and establishes the basis for a gut microbiota-inflammasome-brain axis, whereby the gut microbiota via inflammasome signaling modulate pathways that will alter brain function, and affect depressive- and anxiety-like behaviors. Our data also suggest that further elucidation of the gut microbiota

  4. Bread Affects Clinical Parameters and Induces Gut Microbiome-Associated Personal Glycemic Responses.

    Science.gov (United States)

    Korem, Tal; Zeevi, David; Zmora, Niv; Weissbrod, Omer; Bar, Noam; Lotan-Pompan, Maya; Avnit-Sagi, Tali; Kosower, Noa; Malka, Gal; Rein, Michal; Suez, Jotham; Goldberg, Ben Z; Weinberger, Adina; Levy, Avraham A; Elinav, Eran; Segal, Eran

    2017-06-06

    Bread is consumed daily by billions of people, yet evidence regarding its clinical effects is contradicting. Here, we performed a randomized crossover trial of two 1-week-long dietary interventions comprising consumption of either traditionally made sourdough-leavened whole-grain bread or industrially made white bread. We found no significant differential effects of bread type on multiple clinical parameters. The gut microbiota composition remained person specific throughout this trial and was generally resilient to the intervention. We demonstrate statistically significant interpersonal variability in the glycemic response to different bread types, suggesting that the lack of phenotypic difference between the bread types stems from a person-specific effect. We further show that the type of bread that induces the lower glycemic response in each person can be predicted based solely on microbiome data prior to the intervention. Together, we present marked personalization in both bread metabolism and the gut microbiome, suggesting that understanding dietary effects requires integration of person-specific factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. The Kynurenine Pathway As a Novel Link between Allergy and the Gut Microbiome

    Directory of Open Access Journals (Sweden)

    Aaron P. Van der Leek

    2017-11-01

    Full Text Available In the past few decades, the indoleamine 2,3 dioxygenase (IDO subset of the kynurenine (KYN pathway of tryptophan (TRP metabolism has been the subject of much research in the area of immune tolerance. In this review, we aim to incorporate new findings on this pathway in relation to allergy and the gut microbiome, while providing a comprehensive overview of the pathway itself. Stimulated by interferon gamma, IDO acts as a tolerogenic, immunosuppressive enzyme to attenuate allergic responses by the induction of the KYN-IDO pathway, resultant depletion of TRP, and elevation in KYN metabolites. Acting through the aryl hydrocarbon receptor, KYN metabolites cause T-cell anergy and apoptosis, proliferation of Treg and Th17 cells, and deviation of the Th1/Th2 response, although the outcome is highly dependent on the microenvironment. Moreover, new evidence from germ-free mice and human infants shows that gut microbiota and breast milk are key in determining the functioning of the KYN-IDO pathway. As such, we recommend further research on how this pathway may be a critical link between the microbiome and development of allergy.

  6. Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents.

    Directory of Open Access Journals (Sweden)

    Christian Hoffmann

    Full Text Available Diet influences health as a source of nutrients and toxins, and by shaping the composition of resident microbial populations. Previous studies have begun to map out associations between diet and the bacteria and viruses of the human gut microbiome. Here we investigate associations of diet with fungal and archaeal populations, taking advantage of samples from 98 well-characterized individuals. Diet was quantified using inventories scoring both long-term and recent diet, and archaea and fungi were characterized by deep sequencing of marker genes in DNA purified from stool. For fungi, we found 66 genera, with generally mutually exclusive presence of either the phyla Ascomycota or Basiodiomycota. For archaea, Methanobrevibacter was the most prevalent genus, present in 30% of samples. Several other archaeal genera were detected in lower abundance and frequency. Myriad associations were detected for fungi and archaea with diet, with each other, and with bacterial lineages. Methanobrevibacter and Candida were positively associated with diets high in carbohydrates, but negatively with diets high in amino acids, protein, and fatty acids. A previous study emphasized that bacterial population structure was associated primarily with long-term diet, but high Candida abundance was most strongly associated with the recent consumption of carbohydrates. Methobrevibacter abundance was associated with both long term and recent consumption of carbohydrates. These results confirm earlier targeted studies and provide a host of new associations to consider in modeling the effects of diet on the gut microbiome and human health.

  7. The early infant gut microbiome varies in association with a maternal high-fat diet.

    Science.gov (United States)

    Chu, Derrick M; Antony, Kathleen M; Ma, Jun; Prince, Amanda L; Showalter, Lori; Moller, Michelle; Aagaard, Kjersti M

    2016-08-09

    Emerging evidence suggests that the in utero environment is not sterile as once presumed. Work in the mouse demonstrated transmission of commensal bacteria from mother to fetus during gestation, though it is unclear what modulates this process. We have previously shown in the nonhuman primate that, independent of obesity, a maternal high-fat diet during gestation and lactation persistently shapes the juvenile gut microbiome. We therefore sought to interrogate in a population-based human longitudinal cohort whether a maternal high-fat diet similarly alters the neonatal and infant gut microbiome in early life. A representative cohort was prospectively enrolled either in the early third trimester or intrapartum (n = 163), with a subset consented to longitudinal sampling through the postpartum interval (n = 81). Multiple body site samples, including stool and meconium, were collected from neonates at delivery and by 6 weeks of age. A rapid dietary questionnaire was administered to estimate intake of fat, added sugars, and fiber over the past month (National Health and Examination Survey). DNA was extracted from each infant meconium/stool sample (MoBio) and subjected to 16S rRNA gene sequencing and analysis. On average, the maternal dietary intake of fat ranged from 14.0 to 55.2 %, with an average intake of 33.1 % (σ = 6.1 %). Mothers whose diets significantly differed from the mean (±1 standard deviation) were separated into two distinct groups, a control group (n = 13, μ = 24.4 %) and a high-fat group (n = 13, μ = 43.1 %). Principal coordinate analysis revealed that the microbiome of the neonatal stool at birth (meconium) clustered differently by virtue of maternal gestational diet (PERMANOVA p = 0.001). LEfSe feature selection identified several taxa that discriminated the groups, with a notable relative depletion of Bacteroides in the neonates exposed to a maternal high-fat gestational diet (Student's t-test, p < 0

  8. Gut microbiomes of free-ranging and captive Namibian cheetahs: Diversity, putative functions and occurrence of potential pathogens.

    Science.gov (United States)

    Wasimuddin; Menke, Sebastian; Melzheimer, Jörg; Thalwitzer, Susanne; Heinrich, Sonja; Wachter, Bettina; Sommer, Simone

    2017-10-01

    Although the significance of the gut microbiome for host health is well acknowledged, the impact of host traits and environmental factors on the interindividual variation of gut microbiomes of wildlife species is not well understood. Such information is essential; however, as changes in the composition of these microbial communities beyond the natural range might cause dysbiosis leading to increased susceptibility to infections. We examined the potential influence of sex, age, genetic relatedness, spatial tactics and the environment on the natural range of the gut microbiome diversity in free-ranging Namibian cheetahs (Acinonyx jubatus). We further explored the impact of an altered diet and frequent contact with roaming dogs and cats on the occurrence of potential bacterial pathogens by comparing free-ranging and captive individuals living under the same climatic conditions. Abundance patterns of particular bacterial genera differed between the sexes, and bacterial diversity and richness were higher in older (>3.5 years) than in younger individuals. In contrast, male spatial tactics, which probably influence host exposure to environmental bacteria, had no discernible effect on the gut microbiome. The profound resemblance of the gut microbiome of kin in contrast to nonkin suggests a predominant role of genetics in shaping bacterial community characteristics and functional similarities. We also detected various Operational Taxonomic Units (OTUs) assigned to potential pathogenic bacteria known to cause diseases in humans and wildlife species, such as Helicobacter spp., and Clostridium perfringens. Captive individuals did not differ in their microbial alpha diversity but exhibited higher abundances of OTUs related to potential pathogenic bacteria and shifts in disease-associated functional pathways. Our study emphasizes the need to integrate ecological, genetic and pathogenic aspects to improve our comprehension of the main drivers of natural variation and shifts in

  9. Application of a hierarchical enzyme classification method reveals the role of gut microbiome in human metabolism.

    Science.gov (United States)

    Mohammed, Akram; Guda, Chittibabu

    2015-01-01

    Enzymes are known as the molecular machines that drive the metabolism of an organism; hence identification of the full enzyme complement of an organism is essential to build the metabolic blueprint of that species as well as to understand the interplay of multiple species in an ecosystem. Experimental characterization of the enzymatic reactions of all enzymes in a genome is a tedious and expensive task. The problem is more pronounced in the metagenomic samples where even the species are not adequately cultured or characterized. Enzymes encoded by the gut microbiota play an essential role in the host metabolism; thus, warranting the need to accurately identify and annotate the full enzyme complements of species in the genomic and metagenomic projects. To fulfill this need, we develop and apply a method called ECemble, an ensemble approach to identify enzymes and enzyme classes and study the human gut metabolic pathways. ECemble method uses an ensemble of machine-learning methods to accurately model and predict enzymes from protein sequences and also identifies the enzyme classes and subclasses at the finest resolution. A tenfold cross-validation result shows accuracy between 97 and 99% at different levels in the hierarchy of enzyme classification, which is superior to comparable methods. We applied ECemble to predict the entire complements of enzymes from ten sequenced proteomes including the human proteome. We also applied this method to predict enzymes encoded by the human gut microbiome from gut metagenomic samples, and to study the role played by the microbe-derived enzymes in the human metabolism. After mapping the known and predicted enzymes to canonical human pathways, we identified 48 pathways that have at least one bacteria-encoded enzyme, which demonstrates the complementary role of gut microbiome in human gut metabolism. These pathways are primarily involved in metabolizing dietary nutrients such as carbohydrates, amino acids, lipids, cofactors and

  10. Developing a Bacteroides System for Function-Based Screening of DNA from the Human Gut Microbiome.

    Science.gov (United States)

    Lam, Kathy N; Martens, Eric C; Charles, Trevor C

    2018-01-01

    Functional metagenomics is a powerful method that allows the isolation of genes whose role may not have been predicted from DNA sequence. In this approach, first, environmental DNA is cloned to generate metagenomic libraries that are maintained in Escherichia coli, and second, the cloned DNA is screened for activities of interest. Typically, functional screens are carried out using E. coli as a surrogate host, although there likely exist barriers to gene expression, such as lack of recognition of native promoters. Here, we describe efforts to develop Bacteroides thetaiotaomicron as a surrogate host for screening metagenomic DNA from the human gut. We construct a B. thetaiotaomicron-compatible fosmid cloning vector, generate a fosmid clone library using DNA from the human gut, and show successful functional complementation of a B. thetaiotaomicron glycan utilization mutant. Though we were unable to retrieve the physical fosmid after complementation, we used genome sequencing to identify the complementing genes derived from the human gut microbiome. Our results demonstrate that the use of B. thetaiotaomicron to express metagenomic DNA is promising, but they also exemplify the challenges that can be encountered in the development of new surrogate hosts for functional screening. IMPORTANCE Human gut microbiome research has been supported by advances in DNA sequencing that make it possible to obtain gigabases of sequence data from metagenomes but is limited by a lack of knowledge of gene function that leads to incomplete annotation of these data sets. There is a need for the development of methods that can provide experimental data regarding microbial gene function. Functional metagenomics is one such method, but functional screens are often carried out using hosts that may not be able to express the bulk of the environmental DNA being screened. We expand the range of current screening hosts and demonstrate that human gut-derived metagenomic libraries can be

  11. Application of a hierarchical enzyme classification method reveals the role of gut microbiome in human metabolism

    Science.gov (United States)

    2015-01-01

    Background Enzymes are known as the molecular machines that drive the metabolism of an organism; hence identification of the full enzyme complement of an organism is essential to build the metabolic blueprint of that species as well as to understand the interplay of multiple species in an ecosystem. Experimental characterization of the enzymatic reactions of all enzymes in a genome is a tedious and expensive task. The problem is more pronounced in the metagenomic samples where even the species are not adequately cultured or characterized. Enzymes encoded by the gut microbiota play an essential role in the host metabolism; thus, warranting the need to accurately identify and annotate the full enzyme complements of species in the genomic and metagenomic projects. To fulfill this need, we develop and apply a method called ECemble, an ensemble approach to identify enzymes and enzyme classes and study the human gut metabolic pathways. Results ECemble method uses an ensemble of machine-learning methods to accurately model and predict enzymes from protein sequences and also identifies the enzyme classes and subclasses at the finest resolution. A tenfold cross-validation result shows accuracy between 97 and 99% at different levels in the hierarchy of enzyme classification, which is superior to comparable methods. We applied ECemble to predict the entire complements of enzymes from ten sequenced proteomes including the human proteome. We also applied this method to predict enzymes encoded by the human gut microbiome from gut metagenomic samples, and to study the role played by the microbe-derived enzymes in the human metabolism. After mapping the known and predicted enzymes to canonical human pathways, we identified 48 pathways that have at least one bacteria-encoded enzyme, which demonstrates the complementary role of gut microbiome in human gut metabolism. These pathways are primarily involved in metabolizing dietary nutrients such as carbohydrates, amino acids, lipids

  12. Bacteria of the human gut microbiome catabolize red seaweed glycans with carbohydrate-active enzyme updates from extrinsic microbes.

    Science.gov (United States)

    Hehemann, Jan-Hendrik; Kelly, Amelia G; Pudlo, Nicholas A; Martens, Eric C; Boraston, Alisdair B

    2012-11-27

    Humans host an intestinal population of microbes--collectively referred to as the gut microbiome--which encode the carbohydrate active enzymes, or CAZymes, that are absent from the human genome. These CAZymes help to extract energy from recalcitrant polysaccharides. The question then arises as to if and how the microbiome adapts to new carbohydrate sources when modern humans change eating habits. Recent metagenome analysis of microbiomes from healthy American, Japanese, and Spanish populations identified putative CAZymes obtained by horizontal gene transfer from marine bacteria, which suggested that human gut bacteria evolved to degrade algal carbohydrates-for example, consumed in form of sushi. We approached this hypothesis by studying such a polysaccharide utilization locus (PUL) obtained by horizontal gene transfer by the gut bacterium Bacteroides plebeius. Transcriptomic and growth experiments revealed that the PUL responds to the polysaccharide porphyran from red algae, enabling growth on this carbohydrate but not related substrates like agarose and carrageenan. The X-ray crystallographic and biochemical analysis of two proteins encoded by this PUL, BACPLE_01689 and BACPLE_01693, showed that they are β-porphyranases belonging to glycoside hydrolase families 16 and 86, respectively. The product complex of the GH86 at 1.3 Å resolution highlights the molecular details of porphyran hydrolysis by this new porphyranase. Combined, these data establish experimental support for the argument that CAZymes and associated genes obtained from extrinsic microbes add new catabolic functions to the human gut microbiome.

  13. Discovery of α-L-arabinopyranosidases from human gut microbiome expands the diversity within glycoside hydrolase family 42

    DEFF Research Database (Denmark)

    Viborg, Alexander Holm; Katayama, Takane; Arakawa, Takatoshi

    2017-01-01

    Enzymes of the glycoside hydrolase family 42 (GH42) are widespread in bacteria of the human gut microbiome and play fundamental roles in the decomposition of both milk and plant oligosaccharides. All GH42 enzymes characterized so far have β-galactosidase activity. Here, we report the existence...

  14. Review article: the gut microbiome as a therapeutic target in the pathogenesis and treatment of chronic liver disease.

    Science.gov (United States)

    Woodhouse, C A; Patel, V C; Singanayagam, A; Shawcross, D L

    2018-01-01

    Mortality from chronic liver disease is rising exponentially. The liver is intimately linked to the gut via the portal vein, and exposure to gut microbiota and their metabolites translocating across the gut lumen may impact upon both the healthy and diseased liver. Modulation of gut microbiota could prove to be a potential therapeutic target. To characterise the changes in the gut microbiome that occur in chronic liver disease and to assess the impact of manipulation of the microbiome on the liver. We conducted a PubMed search using search terms including 'microbiome', 'liver' and 'cirrhosis' as well as 'non-alcoholic fatty liver disease', 'steatohepatitis', 'alcohol' and 'primary sclerosing cholangitis'. Relevant articles were also selected from references of articles and review of the ClinicalTrials.gov website. Reduced bacterial diversity, alcohol sensitivity and the development of gut dysbiosis are seen in several chronic liver diseases, including non-alcoholic fatty liver disease, alcohol-related liver disease and primary sclerosing cholangitis. Perturbations in gut commensals could lead to deficient priming of the immune system predisposing the development of immune-mediated diseases. Furthermore, transfer of stool from an animal with the metabolic syndrome may induce steatosis in a healthy counterpart. Patients with cirrhosis develop dysbiosis, small bowel bacterial overgrowth and increased gut wall permeability, allowing bacterial translocation and uptake of endotoxin inducing hepatic and systemic inflammation. Manipulation of the gut microbiota with diet, probiotics or faecal microbiota transplantation to promote the growth of "healthy" bacteria may ameliorate the dysbiosis and alter prognosis. © 2017 John Wiley & Sons Ltd.

  15. Impact of Age, Caloric Restriction, and Influenza Infection on Mouse Gut Microbiome: An Exploratory Study of the Role of Age-Related Microbiome Changes on Influenza Responses

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    Jenna M. Bartley

    2017-09-01

    Full Text Available Immunosenescence refers to age-related declines in the capacity to respond to infections such as influenza (flu. Caloric restriction represents a known strategy to slow many aging processes, including those involving the immune system. More recently, some changes in the microbiome have been described with aging, while the gut microbiome appears to influence responses to flu vaccination and infection. With these considerations in mind, we used a well-established mouse model of flu infection to explore the impact of flu infection, aging, and caloric restriction on the gut microbiome. Young, middle-aged, and aged caloric restricted (CR and ad lib fed (AL mice were examined after a sublethal flu infection. All mice lost 10–20% body weight and, as expected for these early time points, losses were similar at different ages and between diet groups. Cytokine and chemokine levels were also similar with the notable exception of IL-1α, which rose more than fivefold in aged AL mouse serum, while it remained unchanged in aged CR serum. Fecal microbiome phyla abundance profiles were similar in young, middle-aged, and aged AL mice at baseline and at 4 days post flu infection, while increases in Proteobacteria were evident at 7 days post flu infection in all three age groups. CR mice, compared to AL mice in each age group, had increased abundance of Proteobacteria and Verrucomicrobia at all time points. Interestingly, principal coordinate analysis determined that diet exerts a greater effect on the microbiome than age or flu infection. Percentage body weight loss correlated with the relative abundance of Proteobacteria regardless of age, suggesting flu pathogenicity is related to Proteobacteria abundance. Further, several microbial Operational Taxonomic Units from the Bacteroidetes phyla correlated with serum chemokine/cytokines regardless of both diet and age suggesting an interplay between flu-induced systemic inflammation and gut microbiota. These

  16. Chronic chlorpyrifos exposure elicits diet-specific effects on metabolism and the gut microbiome in rats.

    Science.gov (United States)

    Fang, Bing; Li, Jin Wang; Zhang, Ming; Ren, Fa Zheng; Pang, Guo Fang

    2018-01-01

    Chlorpyrifos is a commonly-used pesticide which was reported to interfere with hormone signaling and metabolism, however, little is known about its effect on gut microbiota. In this study, adult male rats fed a normal (NF) or high fat (HF) diet were exposed to 0.3 or 3.0 mg chlorpyrifos/kg bodyweight/day or vehicle alone for 9 weeks. Effects on bodyweight, serum levels of glucose, lipid, cytokines, and gut microbiome community structure were measured. The effects of chlorpyrifos on metabolism were dose- and diet-dependent, with NF-fed rats administered the low dose showing the largest metabolic changes. NF-fed rats exposed to chlorpyrifos exhibited a pro-obesity phenotype compared with their controls, whereas there was no difference in pro-obesity phenotype between HF-fed groups. Chlorpyrifos exposure significantly reduced serum insulin, C-peptide, and amylin concentrations in NF- and HF-fed rats, leaving serum glucose and lipid profiles unaffected. Chlorpyrifos exposure also significantly altered gut microbiota composition, including the abundance of opportunistic pathogens, short chain fatty acid-producing bacteria and other bacteria previously associated with obese and diabetic phenotypes. The abundance of bacteria associated with neurotoxicity and islet injury was also significantly increased by chlorpyrifos. Our results suggest risk assessments for chlorpyrifos exposure should consider other effects in addition to neurotoxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Impact of prematurity and nutrition on the developing gut microbiome and preterm infant growth.

    Science.gov (United States)

    Grier, Alex; Qiu, Xing; Bandyopadhyay, Sanjukta; Holden-Wiltse, Jeanne; Kessler, Haeja A; Gill, Ann L; Hamilton, Brooke; Huyck, Heidie; Misra, Sara; Mariani, Thomas J; Ryan, Rita M; Scholer, Lori; Scheible, Kristin M; Lee, Yi-Horng; Caserta, Mary T; Pryhuber, Gloria S; Gill, Steven R

    2017-12-11

    Identification of factors that influence the neonatal gut microbiome is urgently needed to guide clinical practices that support growth of healthy preterm infants. Here, we examined the influence of nutrition and common practices on the gut microbiota and growth in a cohort of preterm infants. With weekly gut microbiota samples spanning postmenstrual age (PMA) 24 to 46 weeks, we developed two models to test associations between the microbiota, nutrition and growth: a categorical model with three successive microbiota phases (P1, P2, and P3) and a model with two periods (early and late PMA) defined by microbiota composition and PMA, respectively. The more significant associations with phase led us to use a phase-based framework for the majority of our analyses. Phase transitions were characterized by rapid shifts in the microbiota, with transition out of P1 occurring nearly simultaneously with the change from meconium to normal stool. The rate of phase progression was positively associated with gestational age at birth, and delayed transition to a P3 microbiota was associated with growth failure. We found distinct bacterial metabolic functions in P1-3 and significant associations between nutrition, microbiota phase, and infant growth. The phase-dependent impact of nutrition on infant growth along with phase-specific metabolic functions suggests a pioneering potential for improving growth outcomes by tailoring nutrient intake to microbiota phase.

  18. Relationships between diet-related changes in the gut microbiome and cognitive flexibility.

    Science.gov (United States)

    Magnusson, K R; Hauck, L; Jeffrey, B M; Elias, V; Humphrey, A; Nath, R; Perrone, A; Bermudez, L E

    2015-08-06

    Western diets are high in fat and sucrose and can influence behavior and gut microbiota. There is growing evidence that altering the microbiome can influence the brain and behavior. This study was designed to determine whether diet-induced changes in the gut microbiota could contribute to alterations in anxiety, memory or cognitive flexibility. Two-month-old, male C57BL/6 mice were randomly assigned high-fat (42% fat, 43% carbohydrate (CHO), high-sucrose (12% fat, 70% CHO (primarily sucrose) or normal chow (13% kcal fat, 62% CHO) diets. Fecal microbiome analysis, step-down latency, novel object and novel location tasks were performed prior to and 2weeks after diet change. Water maze testing for long- and short-term memory and cognitive flexibility was conducted during weeks 5-6 post-diet change. Some similarities in alterations in the microbiome were seen in both the high-fat and high-sucrose diets (e.g., increased Clostridiales), as compared to the normal diet, but the percentage decreases in Bacteroidales were greater in the high-sucrose diet mice. Lactobacillales was only significantly increased in the high-sucrose diet group and Erysipelotrichales was only significantly affected by the high-fat diet. The high-sucrose diet group was significantly impaired in early development of a spatial bias for long-term memory, short-term memory and reversal training, compared to mice on normal diet. An increased focus on the former platform position was seen in both high-sucrose and high-fat groups during the reversal probe trials. There was no significant effect of diet on step-down, exploration or novel recognitions. Higher percentages of Clostridiales and lower expression of Bacteroidales in high-energy diets were related to the poorer cognitive flexibility in the reversal trials. These results suggest that changes in the microbiome may contribute to cognitive changes associated with eating a Western diet. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights

  19. Gut microbiome and innate immune response patterns in IgE-associated eczema.

    Science.gov (United States)

    West, C E; Rydén, P; Lundin, D; Engstrand, L; Tulic, M K; Prescott, S L

    2015-09-01

    Gut microbiome patterns have been associated with predisposition to eczema potentially through modulation of innate immune signalling. We examined gut microbiome development in the first year of life in relation to innate immune responses and onset of IgE-associated eczema over the first 2.5 years in predisposed children due to maternal atopy [www.anzctr.org.au, trial ID ACTRN12606000280505]. Microbial composition and diversity were analysed with barcoded 16S rRNA 454 pyrosequencing in stool samples in pregnancy and at ages 1 week, 1 month and 12 months in infants (n = 10) who developed IgE-associated eczema and infants who remained free of any allergic symptoms at 2.5 years of age (n = 10). Microbiome data at 1 week and 1 month were analysed in relation to previously assessed immune responses to TLR 2 and 4 ligands at 6 months of age. The relative abundance of Gram-positive Ruminococcaceae was lower at 1 week of age in infants developing IgE-associated eczema, compared with controls (P = 0.0047). At that age, the relative abundance of Ruminococcus was inversely associated with TLR2 induced IL-6 (-0.567, P = 0.042) and TNF-α (-0.597, P = 0.032); there was also an inverse association between the abundance of Proteobacteria (comprising Gram-negative taxa) and TLR4-induced TNF-α (rs = -0.629, P = 0.024). This relationship persisted at 1 month, with inverse associations between the relative abundance of Enterobacteriaceae (within the Proteobacteria phylum) and TLR4-induced TNF-α (rs = -0.697, P = 0.038) and Enterobacteriaceae and IL-6 (rs = -0.709, P = 0.035). Mothers whose infants developed IgE-associated eczema had lower α-diversity of Bacteroidetes (P = 0.04) although this was not seen later in their infants. At 1 year, α-diversity of Actinobacteria was lower in infants with IgE-associated eczema compared with controls (P = 0.002). Our findings suggest that reduced relative abundance of potentially immunomodulatory gut bacteria is associated with exaggerated

  20. An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection.

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    Vijay C Antharam

    Full Text Available Clostridium difficile infection (CDI is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas-chromatography mass spectrometry (GC-MS and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7 and healthy controls (n = 6. From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA, 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub-communities, with each community containing a consortium of organisms that co-occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism.

  1. An Integrated Metabolomic and Microbiome Analysis Identified Specific Gut Microbiota Associated with Fecal Cholesterol and Coprostanol in Clostridium difficile Infection.

    Science.gov (United States)

    Antharam, Vijay C; McEwen, Daniel C; Garrett, Timothy J; Dossey, Aaron T; Li, Eric C; Kozlov, Andrew N; Mesbah, Zhubene; Wang, Gary P

    2016-01-01

    Clostridium difficile infection (CDI) is characterized by dysbiosis of the intestinal microbiota and a profound derangement in the fecal metabolome. However, the contribution of specific gut microbes to fecal metabolites in C. difficile-associated gut microbiome remains poorly understood. Using gas-chromatography mass spectrometry (GC-MS) and 16S rRNA deep sequencing, we analyzed the metabolome and microbiome of fecal samples obtained longitudinally from subjects with Clostridium difficile infection (n = 7) and healthy controls (n = 6). From 155 fecal metabolites, we identified two sterol metabolites at >95% match to cholesterol and coprostanol that significantly discriminated C. difficile-associated gut microbiome from healthy microbiota. By correlating the levels of cholesterol and coprostanol in fecal extracts with 2,395 bacterial operational taxonomic units (OTUs) determined by 16S rRNA sequencing, we identified 63 OTUs associated with high levels of coprostanol and 2 OTUs correlated with low coprostanol levels. Using indicator species analysis (ISA), 31 of the 63 coprostanol-associated bacteria correlated with health, and two Veillonella species were associated with low coprostanol levels that correlated strongly with CDI. These 65 bacterial taxa could be clustered into 12 sub-communities, with each community containing a consortium of organisms that co-occurred with one another. Our studies identified 63 human gut microbes associated with cholesterol-reducing activities. Given the importance of gut bacteria in reducing and eliminating cholesterol from the GI tract, these results support the recent finding that gut microbiome may play an important role in host lipid metabolism.

  2. Pyrosequencing Reveals the Predominance of Pseudomonadaceae in Gut Microbiome of a Gall Midge

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    Raman Bansal

    2014-06-01

    Full Text Available Gut microbes are known to play various roles in insects such as digestion of inaccessible nutrients, synthesis of deficient amino acids, and interaction with ecological environments, including host plants. Here, we analyzed the gut microbiome in Hessian fly, a serious pest of wheat. A total of 3,654 high quality sequences of the V3 hypervariable region of the 16S rRNA gene were obtained through 454-pyrosequencing. From these sequences, 311 operational taxonomic units (OTUs were obtained at the >97% similarity cutoff. In the gut of 1st instar, otu01, a member of Pseudomonas, was predominant, representing 90.2% of total sequences. otu13, an unidentified genus in the Pseudomonadaceae family, represented 1.9% of total sequences. The remaining OTUs were each less than 1%. In the gut of the 2nd instar, otu01 and otu13 decreased to 85.5% and 1.5%, respectively. otu04, a member of Buttiauxella, represented 9.7% of total sequences. The remaining OTUs were each less than 1%. In the gut of the 3rd instar, otu01 and otu13 further decreased to 29.0% and 0%, respectively. otu06, otu08, and otu16, also three members of the Pseudomonadaceae family were 13.2%, 8.6%, and 2.3%, respectively. In addition, otu04 and otu14, two members of the Enterobacteriaceae family, were 4.7% and 2.5%; otu18 and otu20, two members of the Xanthomonadaceae family, were 1.3% and 1.2%, respectively; otu12, a member of Achromobacter, was 4.2%; otu19, a member of Undibacterium, was 1.4%; and otu9, otu10, and otu15, members of various families, were 6.1%, 6.3%, and 1.9%, respectively. The investigation into dynamics of Pseudomonas, the most abundant genera, revealed that its population level was at peak in freshly hatched or 1 day larvae as well as in later developmental stages, thus suggesting a prominent role for this bacterium in Hessian fly development and in its interaction with host plants. This study is the first comprehensive survey on bacteria associated with the gut of a gall

  3. Metagenomic identification of a novel salt tolerance gene from the human gut microbiome which encodes a membrane protein with homology to a brp/blh-family β-carotene 15,15'-monooxygenase.

    Directory of Open Access Journals (Sweden)

    Eamonn P Culligan

    Full Text Available The human gut microbiome consists of at least 3 million non-redundant genes, 150 times that of the core human genome. Herein, we report the identification and characterisation of a novel stress tolerance gene from the human gut metagenome. The locus, assigned brpA, encodes a membrane protein with homology to a brp/blh-family β-carotene monooxygenase. Cloning and heterologous expression of brpA in Escherichia coli confers a significant salt tolerance phenotype. Furthermore, when cultured in the presence of exogenous β-carotene, cell pellets adopt a red/orange pigmentation indicating the incorporation of carotenoids in the cell membrane.

  4. Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders

    Science.gov (United States)

    MacFabe, Derrick F.

    2012-01-01

    Recent evidence suggests potential, but unproven, links between dietary, metabolic, infective, and gastrointestinal factors and the behavioral exacerbations and remissions of autism spectrum disorders (ASDs). Propionic acid (PPA) and its related short-chain fatty acids (SCFAs) are fermentation products of ASD-associated bacteria (Clostridia, Bacteriodetes, Desulfovibrio). SCFAs represent a group of compounds derived from the host microbiome that are plausibly linked to ASDs and can induce widespread effects on gut, brain, and behavior. Intraventricular administration of PPA and SCFAs in rats induces abnormal motor movements, repetitive interests, electrographic changes, cognitive deficits, perseveration, and impaired social interactions. The brain tissue of PPA-treated rats shows a number of ASD-linked neurochemical changes, including innate neuroinflammation, increased oxidative stress, glutathione depletion, and altered phospholipid/acylcarnitine profiles. These directly or indirectly contribute to acquired mitochondrial dysfunction via impairment in carnitine-dependent pathways, consistent with findings in patients with ASDs. Of note, common antibiotics may impair carnitine-dependent processes by altering gut flora favoring PPA-producing bacteria and by directly inhibiting carnitine transport across the gut. Human populations that are partial metabolizers of PPA are more common than previously thought. PPA has further bioactive effects on neurotransmitter systems, intracellular acidification/calcium release, fatty acid metabolism, gap junction gating, immune function, and alteration of gene expression that warrant further exploration. These findings are consistent with the symptoms and proposed underlying mechanisms of ASDs and support the use of PPA infusions in rats as a valid animal model of the condition. Collectively, this offers further support that gut-derived factors, such as dietary or enteric bacterially produced SCFAs, may be plausible environmental

  5. Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Derrick F. MacFabe

    2012-08-01

    Full Text Available Recent evidence suggests potential, but unproven, links between dietary, metabolic, infective, and gastrointestinal factors and the behavioral exacerbations and remissions of autism spectrum disorders (ASDs. Propionic acid (PPA and its related short-chain fatty acids (SCFAs are fermentation products of ASD-associated bacteria (Clostridia, Bacteriodetes, Desulfovibrio. SCFAs represent a group of compounds derived from the host microbiome that are plausibly linked to ASDs and can induce widespread effects on gut, brain, and behavior. Intraventricular administration of PPA and SCFAs in rats induces abnormal motor movements, repetitive interests, electrographic changes, cognitive deficits, perseveration, and impaired social interactions. The brain tissue of PPA-treated rats shows a number of ASD-linked neurochemical changes, including innate neuroinflammation, increased oxidative stress, glutathione depletion, and altered phospholipid/acylcarnitine profiles. These directly or indirectly contribute to acquired mitochondrial dysfunction via impairment in carnitine-dependent pathways, consistent with findings in patients with ASDs. Of note, common antibiotics may impair carnitine-dependent processes by altering gut flora favoring PPA-producing bacteria and by directly inhibiting carnitine transport across the gut. Human populations that are partial metabolizers of PPA are more common than previously thought. PPA has further bioactive effects on neurotransmitter systems, intracellular acidification/calcium release, fatty acid metabolism, gap junction gating, immune function, and alteration of gene expression that warrant further exploration. These findings are consistent with the symptoms and proposed underlying mechanisms of ASDs and support the use of PPA infusions in rats as a valid animal model of the condition. Collectively, this offers further support that gut-derived factors, such as dietary or enteric bacterially produced SCFAs, may be plausible

  6. The new era of treatment for obesity: evidence and expectations for gut microbiome transplantation

    Directory of Open Access Journals (Sweden)

    Thilini N Jayasinghe

    2016-02-01

    Full Text Available Obesity has reached epidemic proportions. Despite a better understanding of the underlying pathophysiology and growing treatment options, a significant proportion of obese patients do not respond to treatment. Recently, microbes residing in the human gastrointestinal tract have been found to act as an endocrine organ, whose composition and functionality may contribute to the development of obesity. Therefore, faecal/gut microbiome transplantation (GMT, which involves the transfer of faeces from a healthy donor to a recipient, is increasingly drawing attention as a potential treatment for obesity. Currently the evidence for GMT effectiveness in the treatment of obesity is preliminary. Here, we summarize benefits, procedures, and issues associated with GMT, with a special focus on obesity.

  7. Disruption of the Gut Microbiome: Clostridium difficile Infection and the Threat of Antibiotic Resistance

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    Priscilla A. Johanesen

    2015-12-01

    Full Text Available Clostridium difficile is well recognized as the leading cause of antibiotic-associated diarrhea, having a significant impact in both health-care and community settings. Central to predisposition to C. difficile infection is disruption of the gut microbiome by antibiotics. Being a Gram-positive anaerobe, C. difficile is intrinsically resistant to a number of antibiotics. Mobile elements encoding antibiotic resistance determinants have also been characterized in this pathogen. While resistance to antibiotics currently used to treat C. difficile infection has not yet been detected, it may be only a matter of time before this occurs, as has been seen with other bacterial pathogens. This review will discuss C. difficile disease pathogenesis, the impact of antibiotic use on inducing disease susceptibility, and the role of antibiotic resistance and mobile elements in C. difficile epidemiology.

  8. Gut microbiome in gestational diabetes: a cross-sectional study of mothers and offspring 5 years postpartum.

    Science.gov (United States)

    Hasan, Sayyid; Aho, Velma; Pereira, Pedro; Paulin, Lars; Koivusalo, Saila B; Auvinen, Petri; Eriksson, Johan G

    2018-01-01

    An altered gut microbiome composition is shown to be associated with various diseases and health outcomes. We compare the gut microbiota of women who developed gestational diabetes mellitus (GDM) with that of those who did not, and the gut microbiota of their offspring, to determine any differences in the composition and diversity of their gut microbiota, which may be correlated with their GDM state. All women were at high risk for GDM and participated in the Finnish Gestational Diabetes Prevention Study (RADIEL). Stool samples were obtained, 5 years postpartum, from 60 GDM-positive women, 68 non-GDM control women, and their children (n = 109), 237 individuals in total. 16S ribosomal RNA gene sequencing was employed to determine the composition of bacterial communities present. Statistical correlations were inferred between clinical variables and microbiota, while taking into account potential confounders. In mothers, no significant differences were observed in microbiota composition between the two groups. Genus Anaerotruncus was increased in children of women with GDM (p microbiome composition when compared with unrelated children, other mothers, or the children compared with each other (p microbiome basis to GDM susceptibility in high-risk women, whereas microbiome differences between the offspring could be of greater biological significance. The heterogeneous nature of the disease could be obscuring potential differences between women. A longer time-series study, with carefully defined subject subgroups, may be an appropriate course of future investigation into GDM and the microbiome. © 2017 Nordic Federation of Societies of Obstetrics and Gynecology.

  9. The Gut Microbiome and HIV-1 Pathogenesis: A Two Way Street

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    Dillon, Stephanie M.; Frank, Daniel N.; Wilson, Cara C.

    2016-01-01

    HIV-1 infection is associated with substantial damage to the gastrointestinal (GI) tract resulting in structural impairment of the epithelial barrier and a disruption of intestinal homeostasis. The accompanying translocation of microbial products and potentially microbes themselves from the lumen into systemic circulation has been linked to immune activation, inflammation, and HIV-1 disease progression. The importance of microbial translocation in the setting of HIV-1 infection has led to a recent focus on understanding how the communities of microbes that make up the intestinal microbiome are altered during HIV-1 infection and how they interact with mucosal immune cells to contribute to inflammation. This review details the dysbiotic intestinal communities associated with HIV-1 infection and their potential link to HIV-1 pathogenesis. We detail studies that begin to address the mechanisms driving microbiota-associated immune activation and inflammation and the various treatment strategies aimed at correcting dysbiosis and improving the overall health of HIV-1 infected individuals. Finally, we discuss how this relatively new field of research can advance to provide a more comprehensive understanding of the contribution of the gut microbiome to HIV-1 pathogenesis. PMID:27755100

  10. Food matters: how the microbiome and gut-brain interaction might impact the development and course of anorexia nervosa.

    Science.gov (United States)

    Herpertz-Dahlmann, Beate; Seitz, Jochen; Baines, John

    2017-09-01

    Anorexia nervosa (AN) is one of the most common chronic illnesses in female adolescents and exhibits the highest mortality risk of all psychiatric disorders. Evidence for the effectiveness of psychotherapeutic or psychopharmacological interventions is weak. Mounting data indicate that the gut microbiome interacts with the central nervous system and the immune system by neuroendocrine, neurotransmitter, neurotrophic and neuroinflammatory afferent and efferent pathways. There is growing evidence that the gut microbiota influences weight regulation and psychopathology, such as anxiety and depression. This article reviews how the gut-brain interaction may impact the development and course of AN. A "leaky gut", characterized by antigens traversing the intestinal wall, was demonstrated in an animal model of AN, and could underlie the low-grade inflammation and increased risk of autoimmune diseases found in AN. Moreover, starvation has a substantial impact on the gut microbiome, and diets used for re-nutrition based on animal products may support the growth of bacteria capable of triggering inflammation. As there is currently no empirically derived agreement on therapeutic re-nourishment in AN, this review discusses how consideration of gut-brain interactions may be important for treatment regarding the determination of target weight, rapidity of weight gain, refeeding methods and composition of the diet which might all be of importance to improve long-term outcome of one of the most chronic psychiatric disorders of adolescence.

  11. Effect of postnatal low-dose exposure to environmental chemicals on the gut microbiome in a rodent model.

    Science.gov (United States)

    Hu, Jianzhong; Raikhel, Vincent; Gopalakrishnan, Kalpana; Fernandez-Hernandez, Heriberto; Lambertini, Luca; Manservisi, Fabiana; Falcioni, Laura; Bua, Luciano; Belpoggi, Fiorella; L Teitelbaum, Susan; Chen, Jia

    2016-06-14

    This proof-of-principle study examines whether postnatal, low-dose exposure to environmental chemicals modifies the composition of gut microbiome. Three chemicals that are widely used in personal care products-diethyl phthalate (DEP), methylparaben (MPB), triclosan (TCS)-and their mixture (MIX) were administered at doses comparable to human exposure to Sprague-Dawley rats from birth through adulthood. Fecal samples were collected at two time points: postnatal day (PND) 62 (adolescence) and PND 181 (adulthood). The gut microbiome was profiled by 16S ribosomal RNA gene sequencing, taxonomically assigned and assessed for diversity. Metagenomic profiling revealed that the low-dose chemical exposure resulted in significant changes in the overall bacterial composition, but in adolescent rats only. Specifically, the individual taxon relative abundance for Bacteroidetes (Prevotella) was increased while the relative abundance of Firmicutes (Bacilli) was reduced in all treated rats compared to controls. Increased abundance was observed for Elusimicrobia in DEP and MPB groups, Betaproteobacteria in MPB and MIX groups, and Deltaproteobacteria in TCS group. Surprisingly, these differences diminished by adulthood (PND 181) despite continuous exposure, suggesting that exposure to the environmental chemicals produced a more profound effect on the gut microbiome in adolescents. We also observed a small but consistent reduction in the bodyweight of exposed rats in adolescence, especially with DEP and MPB treatment (p gut microbiota in adolescent rats; whether these changes lead to downstream health effects requires further investigation.

  12. Adaptive evolution to a high purine and fat diet of carnivorans revealed by gut microbiomes and host genomes.

    Science.gov (United States)

    Zhu, Lifeng; Wu, Qi; Deng, Cao; Zhang, Mengjie; Zhang, Chenglin; Chen, Hua; Lu, Guoqing; Wei, Fuwen

    2018-05-01

    Carnivorous members of the Carnivora reside at the apex of food chains and consume meat-only diets, rich in purine, fats and protein. Here, we aimed to identify potential adaptive evolutionary signatures compatible with high purine and fat metabolism based on analysis of host genomes and symbiotic gut microbial metagenomes. We found that the gut microbiomes of carnivorous Carnivora (e.g., Felidae, Canidae) clustered in the same clade, and other clades comprised omnivorous and herbivorous Carnivora (e.g., badgers, bears and pandas). The relative proportions of genes encoding enzymes involved in uric acid degradation were higher in the gut microbiomes of meat-eating carnivorans than plant-eating species. Adaptive amino acid substitutions in two enzymes, carnitine O-palmitoyltransferase 1 (CPT1A) and lipase F (LIPF), which play a role in fat digestion, were identified in Felidae-Candidae species. Carnivorous carnivorans appear to endure diets high in purines and fats via gut microbiomic and genomic adaptations. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.

  13. Novel Interactions between Gut Microbiome and Host Drug-Processing Genes Modify the Hepatic Metabolism of the Environmental Chemicals Polybrominated Diphenyl Ethers

    Energy Technology Data Exchange (ETDEWEB)

    Li, Cindy Yanfei; Lee, Soowan; Cade, Sara; Kuo, Li-Jung; Schultz, Irvin R.; Bhatt, Deepak K.; Prasad, Bhagwat; Bammler, Theo K.; Cui, Julia Yue

    2017-09-01

    The gut microbiome is a novel frontier in xenobiotic metabolism. Polybrominated diphenyl ethers (PBDEs), especially BDE-47 and BDE-99, are among the most abundant and persistent environmental contaminants that produce a variety of toxicities. Little is known about how the gut microbiome affects the hepatic metabolism of PBDEs and the PBDE-mediated regulation of drug-processing genes (DPGs) in vivo. The goal of this study was to determine the role of gut microbiome in modulating the hepatic biotransformation of PBDEs. Nine-week-old male C57BL/6J conventional (CV) or germ free (GF) mice were treated with vehicle, BDE-47 or BDE-99 (100 μmol/kg) for four days. Following BDE-47 treatment, GF mice had higher level of 5-OH-BDE-47 but lower levels of 4 other metabolites in liver than CV mice; whereas following BDE-99 treatment, GF mice had lower levels of 4 minor metabolites in liver than CV mice. RNA- Seq demonstrated that the hepatic expression of DPGs was regulated by both PBDEs and enterotypes. Under basal condition, the lack of gut microbiome up-regulated the Cyp2c subfamily but down-regulated the Cyp3a subfamily. Following PBDE exposure, certain DPGs were differentially regulated by PBDEs in a gut microbiome-dependent manner. Interestingly, the lack of gut microbiome augmented PBDE-mediated up- regulation of many DPGs, such as Cyp1a2 and Cyp3a11 in mouse liver, which was further confirmed by targeted metabolomics. The lack of gut microbiome also augmented the Cyp3a enzyme activity in liver. In conclusion, our study has unveiled a novel interaction between gut microbiome and the hepatic biotransformation of PBDEs.

  14. The malleable gut microbiome of juvenile rainbow trout (Oncorhynchus mykiss): Diet-dependent shifts of bacterial community structures.

    Science.gov (United States)

    Michl, Stéphanie Céline; Ratten, Jenni-Marie; Beyer, Matt; Hasler, Mario; LaRoche, Julie; Schulz, Carsten

    2017-01-01

    Plant-derived protein sources are the most relevant substitutes for fishmeal in aquafeeds. Nevertheless, the effects of plant based diets on the intestinal microbiome especially of juvenile Rainbow trout (Oncorhynchus mykiss) are yet to be fully investigated. The present study demonstrates, based on 16S rDNA bacterial community profiling, that the intestinal microbiome of juvenile Rainbow trout is strongly affected by dietary plant protein inclusion levels. After first feeding of juveniles with either 0%, 50% or 97% of total dietary protein content derived from plants, statistically significant differences of the bacterial gut community for the three diet-types were detected, both at phylum and order level. The microbiome of juvenile fish consisted mainly of the phyla Proteobacteria, Firmicutes, Bacteroidetes, Fusobacteria and Actinobacteria, and thus fits the salmonid core microbiome suggested in previous studies. Dietary plant proteins significantly enhanced the relative abundance of the orders Lactobacillales, Bacillales and Pseudomonadales. Animal proteins in contrast significantly promoted Bacteroidales, Clostridiales, Vibrionales, Fusobacteriales and Alteromonadales. The overall alpha diversity significantly decreased with increasing plant protein inclusion levels and with age of experimental animals. In order to investigate permanent effects of the first feeding diet-type on the early development of the microbiome, a diet change was included in the study after 54 days, but no such effects could be detected. Instead, the microbiome of juvenile trout fry was highly dependent on the actual diet fed at the time of sampling.

  15. Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Vogt, Josef Korbinian; Kristensen, Mette

    2017-01-01

    Objective To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. Design 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week...... dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory...... of whole grain consumed, in particular with intake of rye. Conclusion Compared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic low-grade inflammation....

  16. Motivations of participants in the citizen science of microbiomics: data from the British Gut Project.

    Science.gov (United States)

    Del Savio, Lorenzo; Prainsack, Barbara; Buyx, Alena

    2017-08-01

    The establishment of databases for research in human microbiomics is dependent on the recruitment of sufficient numbers and diversity of participants. Factors that support or impede participant recruitment in studies of this type have not yet been studied. We report the results of a survey aimed at establishing the motivations of participants in the British Gut Project, a research project that relies on volunteers to provide samples and to help fund the project. The two most frequently reported motivations for participation were altruism and solidarity. Low education levels appeared to be a recruitment obstacle. More than half of our 151 respondents said they would participate in further citizen-science projects; 38% said they would not participate in a similar project if it was for-profit or in a project that did not release data sets in repositories accessible to scientists (30%). The desire to take part in research was reported as a key motivation for participation in the British Gut Project (BGP). Such prosocial motivations can be mobilized for the establishment of large data sets for research.Genet Med advance online publication 26 January 2017.

  17. Comparison of antimicrobial resistant genes in chicken gut microbiome grown on organic and conventional diet

    Directory of Open Access Journals (Sweden)

    Narasimha V. Hegde

    2016-12-01

    Full Text Available Antibiotics are widely used in chicken production for therapeutic purposes, disease prevention and growth promotion, and this may select for drug resistant microorganisms known to spread to humans through consumption of contaminated food. Raising chickens on an organic feed regimen, without the use of antibiotics, is increasingly popular with the consumers. In order to determine the effects of diet regimen on antibiotic resistant genes in the gut microbiome, we analyzed the phylotypes and identified the antimicrobial resistant genes in chicken, grown under conventional and organic dietary regimens. Phylotypes were analyzed from DNA extracted from fecal samples from chickens grown under these dietary conditions. While gut microbiota of chicken raised in both conventional and organic diet exhibited the presence of DNA from members of Proteobacteria and Bacteroidetes, organic diet favored the growth of members of Fusobacteria. Antimicrobial resistance genes were identified from metagenomic libraries following cloning and sequencing of DNA fragments from fecal samples and selecting for the resistant clones (n=340 on media containing different concentrations of eight antibiotics. The antimicrobial resistant genes exhibited diversity in their host distribution among the microbial population and expressed more in samples from chicken grown on a conventional diet at higher concentrations of certain antimicrobials than samples from chicken grown on organic diet. Further studies will elucidate if this phenomena is widespread and whether the antimicrobial resistance is indeed modulated by diet. This may potentially assist in defining strategies for intervention to reduce the prevalence and dissemination of antibiotic resistance genes in the production environment.

  18. Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health?

    Science.gov (United States)

    Bourassa, Megan W; Alim, Ishraq; Bultman, Scott J; Ratan, Rajiv R

    2016-06-20

    As interest in the gut microbiome has grown in recent years, attention has turned to the impact of our diet on our brain. The benefits of a high fiber diet in the colon have been well documented in epidemiological studies, but its potential impact on the brain has largely been understudied. Here, we will review evidence that butyrate, a short-chain fatty acid (SCFA) produced by bacterial fermentation of fiber in the colon, can improve brain health. Butyrate has been extensively studied as a histone deacetylase (HDAC) inhibitor but also functions as a ligand for a subset of G protein-coupled receptors and as an energy metabolite. These diverse modes of action make it well suited for solving the wide array of imbalances frequently encountered in neurological disorders. In this review, we will integrate evidence from the disparate fields of gastroenterology and neuroscience to hypothesize that the metabolism of a high fiber diet in the gut can alter gene expression in the brain to prevent neurodegeneration and promote regeneration. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  19. Succession in the gut microbiome following antibiotic and antibody therapies for Clostridium difficile.

    Science.gov (United States)

    Peterfreund, Gregory L; Vandivier, Lee E; Sinha, Rohini; Marozsan, Andre J; Olson, William C; Zhu, Jun; Bushman, Frederic D

    2012-01-01

    Antibiotic disruption of the intestinal microbiota may cause susceptibility to pathogens that is resolved by progressive bacterial outgrowth and colonization. Succession is central to ecological theory but not widely documented in studies of the vertebrate microbiome. Here, we study succession in the hamster gut after treatment with antibiotics and exposure to Clostridium difficile. C. difficile infection is typically lethal in hamsters, but protection can be conferred with neutralizing antibodies against the A and B toxins. We compare treatment with neutralizing monoclonal antibodies (mAb) to treatment with vancomycin, which prolongs the lives of animals but ultimately fails to protect them from death. We carried out longitudinal deep sequencing analysis and found distinctive waves of succession associated with each form of treatment. Clindamycin sensitization prior to infection was associated with the temporary suppression of the previously dominant Bacteroidales and the fungus Saccinobaculus in favor of Proteobacteria. In mAb-treated animals, C. difficile proliferated before joining Proteobacteria in giving way to re-expanding Bacteroidales and the fungus Wickerhamomyces. However, the Bacteroidales lineages returning by day 7 were different from those that were present initially, and they persisted for the duration of the experiment. Animals treated with vancomycin showed a different set of late-stage lineages that were dominated by Proteobacteria as well as increased disparity between the tissue-associated and luminal cecal communities. The control animals showed no change in their gut microbiota. These data thus suggest different patterns of ecological succession following antibiotic treatment and C. difficile infection.

  20. Succession in the gut microbiome following antibiotic and antibody therapies for Clostridium difficile.

    Directory of Open Access Journals (Sweden)

    Gregory L Peterfreund

    Full Text Available Antibiotic disruption of the intestinal microbiota may cause susceptibility to pathogens that is resolved by progressive bacterial outgrowth and colonization. Succession is central to ecological theory but not widely documented in studies of the vertebrate microbiome. Here, we study succession in the hamster gut after treatment with antibiotics and exposure to Clostridium difficile. C. difficile infection is typically lethal in hamsters, but protection can be conferred with neutralizing antibodies against the A and B toxins. We compare treatment with neutralizing monoclonal antibodies (mAb to treatment with vancomycin, which prolongs the lives of animals but ultimately fails to protect them from death. We carried out longitudinal deep sequencing analysis and found distinctive waves of succession associated with each form of treatment. Clindamycin sensitization prior to infection was associated with the temporary suppression of the previously dominant Bacteroidales and the fungus Saccinobaculus in favor of Proteobacteria. In mAb-treated animals, C. difficile proliferated before joining Proteobacteria in giving way to re-expanding Bacteroidales and the fungus Wickerhamomyces. However, the Bacteroidales lineages returning by day 7 were different from those that were present initially, and they persisted for the duration of the experiment. Animals treated with vancomycin showed a different set of late-stage lineages that were dominated by Proteobacteria as well as increased disparity between the tissue-associated and luminal cecal communities. The control animals showed no change in their gut microbiota. These data thus suggest different patterns of ecological succession following antibiotic treatment and C. difficile infection.

  1. CRISPR-Cas Systems in Bacteroides fragilis, an Important Pathobiont in the Human Gut Microbiome

    Science.gov (United States)

    Tajkarimi, Mehrdad; Wexler, Hannah M.

    2017-01-01

    Background: While CRISPR-Cas systems have been identified in bacteria from a wide variety of ecological niches, there are no studies to describe CRISPR-Cas elements in Bacteroides species, the most prevalent anaerobic bacteria in the lower intestinal tract. Microbes of the genus Bacteroides make up ~25% of the total gut microbiome. Bacteroides fragilis comprises only 2% of the total Bacteroides in the gut, yet causes of >70% of Bacteroides infections. The factors causing it to transition from benign resident of the gut microbiome to virulent pathogen are not well understood, but a combination of horizontal gene transfer (HGT) of virulence genes and differential transcription of endogenous genes are clearly involved. The CRISPR-Cas system is a multi-functional system described in prokaryotes that may be involved in control both of HGT and of gene regulation. Results: Clustered regularly interspaced short palindromic repeats (CRISPR) elements in all strains of B. fragilis (n = 109) with publically available genomes were identified. Three different CRISPR-Cas types, corresponding most closely to Type IB, Type IIIB, and Type IIC, were identified. Thirty-five strains had two CRISPR-Cas types, and three strains included all three CRISPR-Cas types in their respective genomes. The cas1 gene in the Type IIIB system encoded a reverse-transcriptase/Cas1 fusion protein rarely found in prokaryotes. We identified a short CRISPR (3 DR) with no associated cas genes present in most of the isolates; these CRISPRs were found immediately upstream of a hipA/hipB operon and we speculate that this element may be involved in regulation of this operon related to formation of persister cells during antimicrobial exposure. Also, blood isolates of B. fragilis did not have Type IIC CRISPR-Cas systems and had atypical Type IIIB CRISPR-Cas systems that were lacking adjacent cas genes. Conclusions: This is the first systematic report of CRISPR-Cas systems in a wide range of B. fragilis strains

  2. CRISPR-Cas Systems in Bacteroides fragilis, an Important Pathobiont in the Human Gut Microbiome

    Directory of Open Access Journals (Sweden)

    Mehrdad Tajkarimi

    2017-11-01

    Full Text Available Background: While CRISPR-Cas systems have been identified in bacteria from a wide variety of ecological niches, there are no studies to describe CRISPR-Cas elements in Bacteroides species, the most prevalent anaerobic bacteria in the lower intestinal tract. Microbes of the genus Bacteroides make up ~25% of the total gut microbiome. Bacteroides fragilis comprises only 2% of the total Bacteroides in the gut, yet causes of >70% of Bacteroides infections. The factors causing it to transition from benign resident of the gut microbiome to virulent pathogen are not well understood, but a combination of horizontal gene transfer (HGT of virulence genes and differential transcription of endogenous genes are clearly involved. The CRISPR-Cas system is a multi-functional system described in prokaryotes that may be involved in control both of HGT and of gene regulation.Results: Clustered regularly interspaced short palindromic repeats (CRISPR elements in all strains of B. fragilis (n = 109 with publically available genomes were identified. Three different CRISPR-Cas types, corresponding most closely to Type IB, Type IIIB, and Type IIC, were identified. Thirty-five strains had two CRISPR-Cas types, and three strains included all three CRISPR-Cas types in their respective genomes. The cas1 gene in the Type IIIB system encoded a reverse-transcriptase/Cas1 fusion protein rarely found in prokaryotes. We identified a short CRISPR (3 DR with no associated cas genes present in most of the isolates; these CRISPRs were found immediately upstream of a hipA/hipB operon and we speculate that this element may be involved in regulation of this operon related to formation of persister cells during antimicrobial exposure. Also, blood isolates of B. fragilis did not have Type IIC CRISPR-Cas systems and had atypical Type IIIB CRISPR-Cas systems that were lacking adjacent cas genes.Conclusions: This is the first systematic report of CRISPR-Cas systems in a wide range of B

  3. The gut microbiome and mucosal defenses in cats with coronaviruses: a pilot study

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    Sara Meazzi

    2017-05-01

    Full Text Available Feline Infectious Peritonitis (FIP develops from a mutation of enteric feline coronaviruses (FCoVs and an imbalance of the host immune response. The wide polymorphism of FCoVs is associated with the viral replication rate (Licitra et al. 2013.  Changes in the composition of the gut microbiota may induce quali-quantitative modifications in FCoVs and/or different immune profiles (Weese et al., 2015. Few information is available on feline gut microbiome and the association between microbiota and the predisposition to pathological conditions (Ramadan et al., 2014. The aim of this study is to provide preliminary data about the composition of gut microbiota in healthy cats compared with FCoV infected cats (with and without  FIP, in order to evaluate whether changes of gut microbiota may induce changes in FCoV, in its genetic polymorphism and in the mucosal immunity. Screening analyses have been performed on 22 cats: - Routine hematology and biochemistry on EDTA and serum (included electrophoresis and alpha-1-acid glycoprotein measurement for cats suspected with FIP - Nested RT-PCR-3’UTR on frozen faeces - Effusion evaluation - FIV/FeLV serology Due to strict inclusion criteria (cats younger than 2.5 years old, indoor and not assuming antibiotics in the previous two months and based on the results obtained from the complete set of analysis, only 15 cats, specifically 5 cats for each of the following 3 groups: FIP- affected, healthy negative and positive for FCoV, have been recruited to perform the following analyses:  - microbiota analysis through NGS of 16S rRNA gene (V4 region amplicons followed by bioinformatic analysis  -  evaluation of secretory IgA (ELISA kit - phylogenetic analysis of FCoVs S gene sequences Innovative results will be provided on the feline gut microbiota composition. These will be correlated with the presence and genetic polymorphisms of FCoV and mucosal defenses to establish significant correlations between the analysed

  4. The effects of iron fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review.

    Science.gov (United States)

    Paganini, Daniela; Zimmermann, Michael B

    2017-12-01

    In infants and young children in Sub-Saharan Africa, iron-deficiency anemia (IDA) is common, and many complementary foods are low in bioavailable iron. In-home fortification of complementary foods using iron-containing micronutrient powders (MNPs) and oral iron supplementation are both effective strategies to increase iron intakes and reduce IDA at this age. However, these interventions produce large increases in colonic iron because the absorption of their high iron dose (≥12.5 mg) is typically iron supplements and iron fortification with MNPs on the gut microbiome and diarrhea. Iron-containing MNPs and iron supplements can modestly increase diarrhea risk, and in vitro and in vivo studies have suggested that this occurs because increases in colonic iron adversely affect the gut microbiome in that they decrease abundances of beneficial barrier commensal gut bacteria (e.g., bifidobacteria and lactobacilli) and increase the abundance of enterobacteria including entropathogenic Escherichia coli These changes are associated with increased gut inflammation. Therefore, safer formulations of iron-containing supplements and MNPs are needed. To improve MNP safety, the iron dose of these formulations should be reduced while maximizing absorption to retain efficacy. Also, the addition of prebiotics to MNPs is a promising approach to mitigate the adverse effects of iron on the infant gut. © 2017 American Society for Nutrition.

  5. A global comparison of the microbiome compositions of three gut locations in commercial pigs with extreme feed conversion ratios.

    Science.gov (United States)

    Quan, Jianping; Cai, Gengyuan; Ye, Jian; Yang, Ming; Ding, Rongrong; Wang, Xingwang; Zheng, Enqin; Fu, Disheng; Li, Shaoyun; Zhou, Shenping; Liu, Dewu; Yang, Jie; Wu, Zhenfang

    2018-03-14

    In an attempt to increase profits and sustainability in the swine industry, the gut microbiome has become a focus of much research. In this study, we performed a comparative analysis of the gut microbiome in the ileum, cecum, and colon of Duroc × (Landrace × Yorkshire) (DLY) pigs showing two extreme feed conversion ratios (FCRs) using 16S rRNA gene sequencing. The results revealed that the microbial community in the cecum and colon had significantly higher alpha diversity than the ileum. We further identified 11, 55, and 55 operational taxonomic units (OTUs) with significantly different relative abundances between the high and low FCR pigs among the three gut locations, respectively. These OTUs were mainly associated with bacteria that participate in the metabolism of dietary polysaccharides and proteins. We then identified two and nine metabolic pathways that were enriched in the cecum and colon of the high FCR pigs, respectively. The results suggested that the short chain fatty acids and indolic compounds produced by microbial fermentation might influence porcine feed efficiency. These results should improve our understanding of microbiota compositions in the different gut locations of commercial pigs and provide important insights into the effect of gut microbiota on porcine FCRs.

  6. Comparative study of the gut microbiome potentially related to milk protein in Murrah buffaloes (Bubalus bubalis) and Chinese Holstein cattle

    OpenAIRE

    Jiachao Zhang; Chuanbiao Xu; Dongxue Huo; Qisong Hu; Qiannan Peng

    2017-01-01

    Previous studies suggested a close relationship between ruminant gut microbes and the mammary gland. In this study, shotgun metagenomic sequencing was used to reveal the differences in the intestinal microbiome potentially related to milk components in Murrah buffaloes and Chinese Holstein cattle. A PCoA based on the weighted Unifrac distances showed an apparent clustering pattern in the structure of intestinal microbiota between buffalo and cattle. We could attribute the structural differenc...

  7. Risperidone-induced weight gain is mediated through shifts in the gut microbiome and suppression of energy expenditure

    Directory of Open Access Journals (Sweden)

    Sarah M. Bahr

    2015-11-01

    Full Text Available Risperidone is a second-generation antipsychotic that causes weight gain. We hypothesized that risperidone-induced shifts in the gut microbiome are mechanistically involved in its metabolic consequences. Wild-type female C57BL/6J mice treated with risperidone (80 μg/day exhibited significant excess weight gain, due to reduced energy expenditure, which correlated with an altered gut microbiome. Fecal transplant from risperidone-treated mice caused a 16% reduction in total resting metabolic rate in naïve recipients, attributable to suppression of non-aerobic metabolism. Risperidone inhibited growth of cultured fecal bacteria grown anaerobically more than those grown aerobically. Finally, transplant of the fecal phage fraction from risperidone-treated mice was sufficient to cause excess weight gain in naïve recipients, again through reduced energy expenditure. Collectively, these data highlight a major role for the gut microbiome in weight gain following chronic use of risperidone, and specifically implicates the modulation of non-aerobic resting metabolism in this mechanism.

  8. How do agricultural practices impact microbiomes? A case study of antibiotic effects on the swine gut microbiome

    Science.gov (United States)

    The swine gastrointestinal tract is a rich environment containing up to 1000 different species of commensal bacteria. This collection of gut bacteria, or gut microbiota, confers benefits to the host under normal conditions. Disturbance of the gut microbiota is one collateral effect of in-feed anti...

  9. Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Vogt, Josef Korbinian; Kristensen, Mette

    2017-01-01

    Objective To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. Design 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week d...

  10. Altered gut microbiome in a mouse model of Gulf War Illness causes neuroinflammation and intestinal injury via leaky gut and TLR4 activation.

    Directory of Open Access Journals (Sweden)

    Firas Alhasson

    Full Text Available Many of the symptoms of Gulf War Illness (GWI that include neurological abnormalities, neuroinflammation, chronic fatigue and gastrointestinal disturbances have been traced to Gulf War chemical exposure. Though the association and subsequent evidences are strong, the mechanisms that connect exposure to intestinal and neurological abnormalities remain unclear. Using an established rodent model of Gulf War Illness, we show that chemical exposure caused significant dysbiosis in the gut that included increased abundance of phylum Firmicutes and Tenericutes, and decreased abundance of Bacteroidetes. Several gram negative bacterial genera were enriched in the GWI-model that included Allobaculum sp. Altered microbiome caused significant decrease in tight junction protein Occludin with a concomitant increase in Claudin-2, a signature of a leaky gut. Resultant leaching of gut caused portal endotoxemia that led to upregulation of toll like receptor 4 (TLR4 activation in the small intestine and the brain. TLR4 knock out mice and mice that had gut decontamination showed significant decrease in tyrosine nitration and inflammatory mediators IL1β and MCP-1 in both the small intestine and frontal cortex. These events signified that gut dysbiosis with simultaneous leaky gut and systemic endotoxemia-induced TLR4 activation contributes to GW chemical-induced neuroinflammation and gastrointestinal disturbances.

  11. The antibiotic resistome of swine manure is significantly altered by association with the Musca domestica larvae gut microbiome.

    Science.gov (United States)

    Wang, Hang; Sangwan, Naseer; Li, Hong-Yi; Su, Jian-Qiang; Oyang, Wei-Yin; Zhang, Zhi-Jian; Gilbert, Jack A; Zhu, Yong-Guan; Ping, Fan; Zhang, Han-Luo

    2017-01-01

    The overuse of antibiotics as veterinary feed additives is potentially contributing to a significant reservoir of antibiotic resistance in agricultural farmlands via the application of antibiotic-contaminated manure. Vermicomposting of swine manure using housefly larvae is a promising biotechnology for waste reduction and control of antibiotic pollution. To determine how vermicomposting influences antibiotic resistance traits in swine manure, we explored the resistome and associated bacterial community dynamics during larvae gut transit over 6 days of treatment. In total, 94 out of 158 antibiotic resistance genes (ARGs) were significantly attenuated (by 85%), while 23 were significantly enriched (3.9-fold) following vermicomposting. The manure-borne bacterial community showed a decrease in the relative abundance of Bacteroidetes, and an increase in Proteobacteria, specifically Ignatzschineria, following gut transit. ARG attenuation was significantly correlated with changes in microbial community succession, especially reduction in Clostridiales and Bacteroidales. Six genomes were assembled from the manure, vermicompost (final product) and gut samples, including Pseudomonas, Providencia, Enterococcus, Bacteroides and Alcanivorax. Transposon-linked ARGs were more abundant in gut-associated bacteria compared with those from manure and vermicompost. Further, ARG-transposon gene cassettes had a high degree of synteny between metagenomic assemblies from gut and vermicompost samples, highlighting the significant contribution of gut microbiota through horizontal gene transfer to the resistome of vermicompost. In conclusion, the larvae gut microbiome significantly influences manure-borne community succession and the antibiotic resistome during animal manure processing.

  12. Longitudinal development of the gut microbiome and metabolome in preterm neonates with late onset sepsis and healthy controls.

    Science.gov (United States)

    Stewart, Christopher J; Embleton, Nicholas D; Marrs, Emma C L; Smith, Daniel P; Fofanova, Tatiana; Nelson, Andrew; Skeath, Tom; Perry, John D; Petrosino, Joseph F; Berrington, Janet E; Cummings, Stephen P

    2017-07-12

    Late onset sepsis (LOS) in preterm infants is associated with considerable morbidity and mortality. While studies have implicated gut bacteria in the aetiology of the disease, functional analysis and mechanistic insights are generally lacking. We performed temporal bacterial (n = 613) and metabolomic (n = 63) profiling on extensively sampled stool from 7 infants with LOS and 28 matched healthy (no LOS or NEC) controls. The bacteria isolated in diagnostic blood culture usually corresponded to the dominant bacterial genera in the gut microbiome. Longitudinal changes were monitored based on preterm gut community types (PGCTs), where control infants had an increased number of PGCTs compared to LOS infants (P = 0.011). PGCT 6, characterised by Bifidobacteria dominance, was only present in control infants. Metabolite profiles differed between LOS and control infants at diagnosis and 7 days later, but not 7 days prior to diagnosis. Bifidobacteria was positively correlated with control metabolites, including raffinose, sucrose, and acetic acid. Using multi-omic analysis, we show that the gut microbiome is involved in the pathogenesis of LOS. While the causative agent of LOS varies, it is usually abundant in the gut. Bifidobacteria dominance was associated with control infants, and the presence of this organism may directly protect, or act as a marker for protection, against gut epithelial translocation. While the metabolomic data is preliminary, the findings support that gut development and protection in preterm infants is associated with increased in prebiotic oligosaccharides (e.g. raffinose) and the growth of beneficial bacteria (e.g. Bifidobacterium).

  13. Metagenomic systems biology of the human gut microbiome reveals topological shifts associated with obesity and inflammatory bowel disease.

    Science.gov (United States)

    Greenblum, Sharon; Turnbaugh, Peter J; Borenstein, Elhanan

    2012-01-10

    The human microbiome plays a key role in a wide range of host-related processes and has a profound effect on human health. Comparative analyses of the human microbiome have revealed substantial variation in species and gene composition associated with a variety of disease states but may fall short of providing a comprehensive understanding of the impact of this variation on the community and on the host. Here, we introduce a metagenomic systems biology computational framework, integrating metagenomic data with an in silico systems-level analysis of metabolic networks. Focusing on the gut microbiome, we analyze fecal metagenomic data from 124 unrelated individuals, as well as six monozygotic twin pairs and their mothers, and generate community-level metabolic networks of the microbiome. Placing variations in gene abundance in the context of these networks, we identify both gene-level and network-level topological differences associated with obesity and inflammatory bowel disease (IBD). We show that genes associated with either of these host states tend to be located at the periphery of the metabolic network and are enriched for topologically derived metabolic "inputs." These findings may indicate that lean and obese microbiomes differ primarily in their interface with the host and in the way they interact with host metabolism. We further demonstrate that obese microbiomes are less modular, a hallmark of adaptation to low-diversity environments. We additionally link these topological variations to community species composition. The system-level approach presented here lays the foundation for a unique framework for studying the human microbiome, its organization, and its impact on human health.

  14. Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome

    DEFF Research Database (Denmark)

    Roager, Henrik Munch; Vogt, Josef K; Kristensen, Mette

    2018-01-01

    OBJECTIVE: To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. DESIGN: 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week...... dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory.......0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did...

  15. Metagenomic and metabolomic analysis of the toxic effects of trichloroacetamide-induced gut microbiome and urine metabolome perturbations in mice.

    Science.gov (United States)

    Zhang, Yan; Zhao, Fuzheng; Deng, Yongfeng; Zhao, Yanping; Ren, Hongqiang

    2015-04-03

    Disinfection byproducts (DBPs) in drinking water have been linked to various diseases, including colon, colorectal, rectal, and bladder cancer. Trichloroacetamide (TCAcAm) is an emerging nitrogenous DBP, and our previous study found that TCAcAm could induce some changes associated with host-gut microbiota co-metabolism. In this study, we used an integrated approach combining metagenomics, based on high-throughput sequencing, and metabolomics, based on nuclear magnetic resonance (NMR), to evaluate the toxic effects of TCAcAm exposure on the gut microbiome and urine metabolome. High-throughput sequencing revealed that the gut microbiome's composition and function were significantly altered after TCAcAm exposure for 90 days in Mus musculus mice. In addition, metabolomic analysis showed that a number of gut microbiota-related metabolites were dramatically perturbed in the urine of the mice. These results may provide novel insight into evaluating the health risk of environmental pollutants as well as revealing the potential mechanism of TCAcAm's toxic effects.

  16. Variations in the post-weaning human gut metagenome profile as result of Bifidobacterium acquisition in the Western microbiome

    Directory of Open Access Journals (Sweden)

    Matteo Soverini

    2016-07-01

    Full Text Available Studies of the gut microbiome variation among human populations revealed the existence of robust compositional and functional layouts matching the three subsistence strategies that describe a trajectory of changes across our recent evolutionary history: hunting and gathering, rural agriculture, and urban post-industrialized agriculture. In particular, beside the overall reduction of ecosystem diversity, the gut microbiome of Western industrial populations is typically characterized by the loss of Treponema and the acquisition of Bifidobacterium as an abundant inhabitant of the post-weaning gut microbial ecosystem. In order to advance the hypothesis about the possible adaptive nature of this exchange, here we explore specific functional attributes that correspond to the mutually exclusive presence of Treponema and Bifidobacterium using publically available gut metagenomic data from Hadza hunter-gatherers and urban industrial Italians. According to our findings, Bifidobacterium provides the enteric ecosystem with a diverse panel of saccharolytic functions, well suited to the array of gluco- and galacto-based saccharides that abound in the Western diet. On the other hand, the metagenomic functions assigned to Treponema are more predictive of a capacity to incorporate complex polysaccharides, such as those found in unrefined plant foods, which are consistently incorporated in the Hadza diet. Finally, unlike Treponema, the Bifidobacterium metagenome functions include genes that permit the establishment of microbe-host immunological cross-talk, suggesting recent co-evolutionary events between the human immune system and Bifidobacterium that are adaptive in the context of agricultural subsistence and sedentary societies.

  17. The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome

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    Timothy A. Johnson

    2017-08-01

    Full Text Available Carbadox is a quinoxaline-di-N-oxide antibiotic fed to over 40% of young pigs in the United States that has been shown to induce phage DNA transduction in vitro; however, the effects of carbadox on swine microbiome functions are poorly understood. We investigated the in vivo longitudinal effects of carbadox on swine gut microbial gene expression (fecal metatranscriptome and phage population dynamics (fecal dsDNA viromes. Microbial metagenome, transcriptome, and virome sequences were annotated for taxonomic inference and gene function by using FIGfam (isofunctional homolog sequences and SEED subsystems databases. When the beta diversities of microbial FIGfam annotations were compared, the control and carbadox communities were distinct 2 days after carbadox introduction. This effect was driven by carbadox-associated lower expression of FIGfams (n = 66 related to microbial respiration, carbohydrate utilization, and RNA metabolism (q < 0.1, suggesting bacteriostatic or bactericidal effects within certain populations. Interestingly, carbadox treatment caused greater expression of FIGfams related to all stages of the phage lytic cycle 2 days following the introduction of carbadox (q ≤0.07, suggesting the carbadox-mediated induction of prophages and phage DNA recombination. These effects were diminished by 7 days of continuous carbadox in the feed, suggesting an acute impact. Additionally, the viromes included a few genes that encoded resistance to tetracycline, aminoglycoside, and beta-lactam antibiotics but these did not change in frequency over time or with treatment. The results show decreased bacterial growth and metabolism, prophage induction, and potential transduction of bacterial fitness genes in swine gut bacterial communities as a result of carbadox administration.

  18. The In-Feed Antibiotic Carbadox Induces Phage Gene Transcription in the Swine Gut Microbiome

    Science.gov (United States)

    Johnson, Timothy A.; Severin, Andrew J.; Bayles, Darrell O.; Nasko, Daniel J.; Wommack, K. Eric; Howe, Adina

    2017-01-01

    ABSTRACT Carbadox is a quinoxaline-di-N-oxide antibiotic fed to over 40% of young pigs in the United States that has been shown to induce phage DNA transduction in vitro; however, the effects of carbadox on swine microbiome functions are poorly understood. We investigated the in vivo longitudinal effects of carbadox on swine gut microbial gene expression (fecal metatranscriptome) and phage population dynamics (fecal dsDNA viromes). Microbial metagenome, transcriptome, and virome sequences were annotated for taxonomic inference and gene function by using FIGfam (isofunctional homolog sequences) and SEED subsystems databases. When the beta diversities of microbial FIGfam annotations were compared, the control and carbadox communities were distinct 2 days after carbadox introduction. This effect was driven by carbadox-associated lower expression of FIGfams (n = 66) related to microbial respiration, carbohydrate utilization, and RNA metabolism (q < 0.1), suggesting bacteriostatic or bactericidal effects within certain populations. Interestingly, carbadox treatment caused greater expression of FIGfams related to all stages of the phage lytic cycle 2 days following the introduction of carbadox (q ≤0.07), suggesting the carbadox-mediated induction of prophages and phage DNA recombination. These effects were diminished by 7 days of continuous carbadox in the feed, suggesting an acute impact. Additionally, the viromes included a few genes that encoded resistance to tetracycline, aminoglycoside, and beta-lactam antibiotics but these did not change in frequency over time or with treatment. The results show decreased bacterial growth and metabolism, prophage induction, and potential transduction of bacterial fitness genes in swine gut bacterial communities as a result of carbadox administration. PMID:28790203

  19. An abundance of Epsilonproteobacteria revealed in the gut microbiome of the laboratory cultured sea urchin, Lytechinus variegatus

    Science.gov (United States)

    Hakim, Joseph A.; Koo, Hyunmin; Dennis, Lacey N.; Kumar, Ranjit; Ptacek, Travis; Morrow, Casey D.; Lefkowitz, Elliot J.; Powell, Mickie L.; Bej, Asim K.; Watts, Stephen A.

    2015-01-01

    In this study, we have examined the bacterial community composition of the laboratory cultured sea urchin Lytechinus variegatus gut microbiome and its culture environment using NextGen amplicon sequencing of the V4 segment of the 16S rRNA gene, and downstream bioinformatics tools. Overall, the gut and tank water was dominated by Proteobacteria, whereas the feed consisted of a co-occurrence of Proteobacteria and Firmicutes at a high abundance. The gut tissue represented Epsilonproteobacteria as dominant, with order Campylobacterales at the highest relative abundance (>95%). However, the pharynx tissue was dominated by class Alphaproteobacteria. The gut digesta and egested fecal pellets had a high abundance of class Gammaproteobacteria, from which Vibrio was found to be the primary genus, and Epsilonproteobacteria, with genus Arcobacter occurring at a moderate level. At the class level, the tank water was dominated by Gammaproteobacteria, and the feed by Alphaproteobacteria. Multi-Dimensional Scaling analysis showed that the microbial community of the gut tissue clustered together, as did the pharynx tissue to the feed. The gut digesta and egested fecal pellets showed a similarity relationship to the tank water. Further analysis of Campylobacterales at a lower taxonomic level using the oligotyping method revealed 37 unique types across the 10 samples, where Oligotype 1 was primarily represented in the gut tissue. BLAST analysis identified Oligotype 1 to be Arcobacter sp., Sulfuricurvum sp., and Arcobacter bivalviorum at an identity level >90%. This study showed that although distinct microbial communities are evident across multiple components of the sea urchin gut ecosystem, there is a noticeable correlation between the overall microbial communities of the gut with the sea urchin L. variegatus culture environment. PMID:26528245

  20. An abundance of Epsilonproteobacteria revealed in the gut microbiome of the laboratory cultured sea urchin, Lytechinus variegatus

    Directory of Open Access Journals (Sweden)

    Joseph Antoine Hakim

    2015-10-01

    Full Text Available In this study, we have examined the bacterial community composition in the laboratory cultured sea urchin Lytechinus variegatus gut microbiome and its culture environment using NextGen amplicon sequencing of the V4 segment of the 16S rRNA gene, and downstream bioinformatics tools. Overall, the gut and tank water was dominated by Proteobacteria, whereas the feed consisted of a co-occurrence of Proteobacteria and Firmicutes at a high abundance. The gut tissue represented Epsilonproteobacteria as dominant, with order Campylobacterales at the highest relative abundance (>95%. However, the pharynx tissue was dominated by class Alphaproteobacteria. The gut digesta and egested fecal pellets had a high abundance of class Gammaproteobacteria, from which Vibrio was found to be the primary genus, and Epsilonproteobacteria, with genus Arcobacter occurring at a moderate level. At the class level, the tank water was dominated by Gammaproteobacteria, and the feed by Alphaproteobacteria. Multi-Dimensional Scaling analysis showed that the microbial community of the gut tissue clustered together, as did the pharynx tissue to the feed. The gut digesta and egested fecal pellets showed a similar relationship to the tank water. Further analysis of Campylobacterales at a lower taxonomic level using the oligotyping method revealed 37 unique types across the ten samples, where Oligotype 1 was primarily represented in the gut tissue. BLAST analysis identified Oligotype 1 to be Arcobacter sp., Sulfuricurvum sp., and Arcobacter bivalviorum at an identity level >90%. This study showed that although distinct microbial communities were evident across multiple components of the sea urchin gut ecosystem, there is a noticeable correlation between the overall microbial communities of the gut with the sea urchin L. variegatus culture environment.

  1. Probiotic modulation of symbiotic gut microbial–host metabolic interactions in a humanized microbiome mouse model

    Science.gov (United States)

    Martin, Francois-Pierre J; Wang, Yulan; Sprenger, Norbert; Yap, Ivan K S; Lundstedt, Torbjörn; Lek, Per; Rezzi, Serge; Ramadan, Ziad; van Bladeren, Peter; Fay, Laurent B; Kochhar, Sunil; Lindon, John C; Holmes, Elaine; Nicholson, Jeremy K

    2008-01-01

    The transgenomic metabolic effects of exposure to either Lactobacillus paracasei or Lactobacillus rhamnosus probiotics have been measured and mapped in humanized extended genome mice (germ-free mice colonized with human baby flora). Statistical analysis of the compartmental fluctuations in diverse metabolic compartments, including biofluids, tissue and cecal short-chain fatty acids (SCFAs) in relation to microbial population modulation generated a novel top-down systems biology view of the host response to probiotic intervention. Probiotic exposure exerted microbiome modification and resulted in altered hepatic lipid metabolism coupled with lowered plasma lipoprotein levels and apparent stimulated glycolysis. Probiotic treatments also altered a diverse range of pathways outcomes, including amino-acid metabolism, methylamines and SCFAs. The novel application of hierarchical-principal component analysis allowed visualization of multicompartmental transgenomic metabolic interactions that could also be resolved at the compartment and pathway level. These integrated system investigations demonstrate the potential of metabolic profiling as a top-down systems biology driver for investigating the mechanistic basis of probiotic action and the therapeutic surveillance of the gut microbial activity related to dietary supplementation of probiotics. PMID:18197175

  2. Gut microbiome composition is associated with cardiac disease in zoo-housed western lowland gorillas (Gorilla gorilla gorilla).

    Science.gov (United States)

    Krynak, Katherine L; Burke, David J; Martin, Ryan A; Dennis, Patricia M

    2017-08-15

    Cardiac disease is a leading cause of mortality in zoo-housed western lowland gorillas (Gorilla gorilla gorilla). The gut microbiome is associated with cardiac disease in humans and similarly the gut microbiome may be associated with cardiac diseases in close relatives of humans, such as gorillas. We assessed the relationship between cardiac disease and gut bacterial composition in eight zoo-housed male western lowland gorillas (N = 4 with and N = 4 without cardiac disease) utilizing 16S rRNA gene analysis on the Illumina MiSeq sequencing platform. We found bacterial composition differences between gorillas with and without cardiac disease. Bacterial operational taxonomic units from phyla Bacteroidetes, Spirochaetes, Proteobacteria and Firmicutes were significant indicators of cardiac disease. Our results suggest that further investigations between diet and cardiac disease could improve the management and health of zoo-housed populations of this endangered species. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Geriatric Respondents and Non-Respondents To Probiotic Intervention Can Be Differentiated By Inherent Gut Microbiome Composition

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    Suja eSenan

    2015-09-01

    Full Text Available Scope: Probiotic interventions are known to have been shown to influence the composition of the intestinal microbiota in geriatrics. The growing concern is the apparent variation in response to identical strain dosage among human volunteers. One factor that governs this variation is the host gut microbiome. In this study, we attempted to define a core gut metagenome which could act as a predisposition signature marker of inherent bacterial community that can help predict the success of a probiotic intervention. Methods and Results: To characterize the geriatric gut microbiome we designed primers targeting the 16S rRNA hypervariable region V2-V3 followed by semiconductor sequencing using Ion Torrent PGM. Among respondents and non- respondents the chief genera of phylum Firmicutes that showed significant differences are Lactobacillus, Clostridium, Eubacterium, and Blautia (q< 0.002 while in the genera of phylum Proteobacteria included Shigella, Escherichia, Burkholderia and Camphylobacter (q <0.002. Conclusion: We have identified potential microbial biomarkers and taxonomic patterns that correlate with a positive response to probiotic intervention in geriatric volunteers. Future work with larger cohorts of geriatrics with diverse dietary influences could reveal the potential of the signature patterns of microbiota for personalized nutrition.

  4. The Gut Microbiomes of Two Pachysoma MacLeay Desert Dung Beetle Species (Coleoptera: Scarabaeidae: Scarabaeinae Feeding on Different Diets.

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    Philippa Z N Franzini

    Full Text Available Micro-organisms inhabiting animal guts benefit from a protected and nutrient-rich environment while assisting the host with digestion and nutrition. In this study we compare, for the first time, the bacterial and fungal gut communities of two species of the small desert dung beetle genus Pachysoma feeding on different diets: the detritivorous P. endroedyi and the dry-dung-feeding P. striatum. Whole-gut microbial communities from 5 individuals of each species were assessed using 454 pyrosequencing of the bacterial 16S rRNA gene and fungal ITS gene regions. The two bacterial communities were significantly different, with only 3.7% of operational taxonomic units shared, and displayed intra-specific variation. The number of bacterial phyla present within the guts of P. endroedyi and P. striatum individuals ranged from 6-11 and 4-7, respectively. Fungal phylotypes could only be detected within the gut of P. striatum. Although the role of host phylogeny in Pachysoma microbiome assembly remains unknown, evidence presented in this study suggests that host diet may be a deterministic factor.

  5. TCDD modulation of gut microbiome correlated with liver and immune toxicity in streptozotocin (STZ)-induced hyperglycemic mice

    International Nuclear Information System (INIS)

    Lefever, Daniel E.; Xu, Joella; Chen, Yingjia; Huang, Guannan; Tamas, Nagy; Guo, Tai L.

    2016-01-01

    An increasing body of evidence has shown the important role of the gut microbiome in mediating toxicity following environmental contaminant exposure. The goal of this study was to determine if the adverse metabolic effects of chronic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure would be sufficient to exacerbate hyperglycemia, and to further determine if these outcomes were attributable to the gut microbiota alteration. Adult male CD-1 mice were exposed to TCDD (6 μg/kg body weight biweekly) by gavage and injected (i.p.) with STZ (4 × 50 mg/kg body weight) to induced hyperglycemia. 16S rRNA sequencing was used to characterize the changes in the microbiome community composition. Glucose monitoring, flow cytometry, histopathology, and organ characterization were performed to determine the deleterious phenotypic changes of TCDD exposure. Chronic TCDD treatment did not appear to exacerbate STZ-induced hyperglycemia as blood glucose levels were slightly reduced in the TCDD treated mice; however, polydipsia and polyphagia were observed. Importantly, TCDD exposure caused a dramatic change in microbiota structure, as characterized at the phylum level by increasing Firmicutes and decreasing Bacteroidetes while at the family level most notably by increasing Lactobacillaceae and Desulfovibrionaceae, and decreasing Prevotellaceae and ACK M1. The changes in microbiota were further found to be broadly associated with phenotypic changes seen from chronic TCDD treatment. In particular, the phylum level Bacteroidetes to Firmicutes ratio negatively correlated with both liver weight and liver pathology, and positively associated with %CD3 + NK + T cells, a key mediator of host-microbial interactions. Collectively, these findings suggest that the dysregulated gut microbiome may contribute to the deleterious effects (e.g., liver toxicity) seen with TCDD exposure. - Highlights: • TCDD promoted wasting syndrome. • TCDD decreased hyperglycemia. • TCDD exposure caused

  6. TCDD modulation of gut microbiome correlated with liver and immune toxicity in streptozotocin (STZ)-induced hyperglycemic mice

    Energy Technology Data Exchange (ETDEWEB)

    Lefever, Daniel E.; Xu, Joella; Chen, Yingjia [Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia, Athens, GA 30602-7382 (United States); Huang, Guannan [Department of Environmental Health Sciences, University of Georgia, Athens, GA 30602-7382 (United States); Tamas, Nagy [Department of Veterinary Pathology, University of Georgia, Athens, GA 30602-7382 (United States); Guo, Tai L., E-mail: tlguo1@uga.edu [Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia, Athens, GA 30602-7382 (United States)

    2016-08-01

    An increasing body of evidence has shown the important role of the gut microbiome in mediating toxicity following environmental contaminant exposure. The goal of this study was to determine if the adverse metabolic effects of chronic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure would be sufficient to exacerbate hyperglycemia, and to further determine if these outcomes were attributable to the gut microbiota alteration. Adult male CD-1 mice were exposed to TCDD (6 μg/kg body weight biweekly) by gavage and injected (i.p.) with STZ (4 × 50 mg/kg body weight) to induced hyperglycemia. 16S rRNA sequencing was used to characterize the changes in the microbiome community composition. Glucose monitoring, flow cytometry, histopathology, and organ characterization were performed to determine the deleterious phenotypic changes of TCDD exposure. Chronic TCDD treatment did not appear to exacerbate STZ-induced hyperglycemia as blood glucose levels were slightly reduced in the TCDD treated mice; however, polydipsia and polyphagia were observed. Importantly, TCDD exposure caused a dramatic change in microbiota structure, as characterized at the phylum level by increasing Firmicutes and decreasing Bacteroidetes while at the family level most notably by increasing Lactobacillaceae and Desulfovibrionaceae, and decreasing Prevotellaceae and ACK M1. The changes in microbiota were further found to be broadly associated with phenotypic changes seen from chronic TCDD treatment. In particular, the phylum level Bacteroidetes to Firmicutes ratio negatively correlated with both liver weight and liver pathology, and positively associated with %CD3{sup +} NK{sup +} T cells, a key mediator of host-microbial interactions. Collectively, these findings suggest that the dysregulated gut microbiome may contribute to the deleterious effects (e.g., liver toxicity) seen with TCDD exposure. - Highlights: • TCDD promoted wasting syndrome. • TCDD decreased hyperglycemia. • TCDD exposure

  7. Preterm Gut Microbiome Depending on Feeding Type: Significance of Donor Human Milk

    Directory of Open Access Journals (Sweden)

    Anna Parra-Llorca

    2018-06-01

    Full Text Available Preterm microbial colonization is affected by gestational age, antibiotic treatment, type of birth, but also by type of feeding. Breast milk has been acknowledged as the gold standard for human nutrition. In preterm infants breast milk has been associated with improved growth and cognitive development and a reduced risk of necrotizing enterocolitis and late onset sepsis. In the absence of their mother’s own milk (MOM, pasteurized donor human milk (DHM could be the best available alternative due to its similarity to the former. However, little is known about the effect of DHM upon preterm microbiota and potential biological implications. Our objective was to determine the impact of DHM upon preterm gut microbiota admitted in a referral neonatal intensive care unit (NICU. A prospective observational cohort study in NICU of 69 neonates <32 weeks of gestation and with a birth weight ≤1,500 g was conducted. Neonates were classified in three groups according to feeding practices consisting in their MOM, DHM, or formula. Fecal samples were collected when full enteral feeding (defined as ≥150 cc/kg/day was achieved. Gut microbiota composition was analyzed by 16S rRNA gene sequencing. Despite the higher variability, no differences in microbial diversity and richness were found, although feeding type significantly influenced the preterm microbiota composition and predictive functional profiles. Preterm infants fed MOM showed a significant greater presence of Bifidobacteriaceae and lower of Staphylococcaceae, Clostridiaceae, and Pasteurellaceae compared to preterm fed DHM. Formula fed microbial profile was different to those observed in preterm fed MOM. Remarkably, preterm infants fed DHM showed closer microbial profiles to preterm fed their MOM. Inferred metagenomic analyses showed higher presence of Bifidobacterium genus in mother’s milk group was related to enrichment in the Glycan biosynthesis and metabolism pathway that was not identified in

  8. Geographical patterns of the standing and active human gut microbiome in health and IBD.

    Science.gov (United States)

    Rehman, Ateequr; Rausch, Philipp; Wang, Jun; Skieceviciene, Jurgita; Kiudelis, Gediminas; Bhagalia, Ketan; Amarapurkar, Deepak; Kupcinskas, Limas; Schreiber, Stefan; Rosenstiel, Philip; Baines, John F; Ott, Stephan

    2016-02-01

    A global increase of IBD has been reported, especially in countries that previously had low incidence rates. Also, the knowledge of the human gut microbiome is steadily increasing, however, limited information regarding its variation on a global scale is available. In the light of the microbial involvement in IBDs, we aimed to (1) identify shared and distinct IBD-associated mucosal microbiota patterns from different geographical regions including Europe (Germany, Lithuania) and South Asia (India) and (2) determine whether profiling based on 16S rRNA transcripts provides additional resolution, both of which may hold important clinical relevance. In this study, we analyse a set of 89 mucosal biopsies sampled from individuals of German, Lithuanian and Indian origins, using bacterial community profiling of a roughly equal number of healthy controls, patients with Crohn's disease and UC from each location, and analyse 16S rDNA and rRNA as proxies for standing and active microbial community structure, respectively. We find pronounced population-specific as well as general disease patterns in the major phyla and patterns of diversity, which differ between the standing and active communities. The geographical origin of samples dominates the patterns of β diversity with locally restricted disease clusters and more pronounced effects in the active microbial communities. However, two genera belonging to the Clostridium leptum subgroup, Faecalibacteria and Papillibacter, display consistent patterns with respect to disease status and may thus serve as reliable 'microbiomarkers'. These analyses reveal important interactions of patients' geographical origin and disease in the interpretation of disease-associated changes in microbial communities and highlight the added value of analysing communities on both the 16S rRNA gene (DNA) and transcript (RNA) level. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go

  9. Systems Modeling of Interactions between Mucosal Immunity and the Gut Microbiome during Clostridium difficile Infection.

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    Andrew Leber

    Full Text Available Clostridium difficile infections are associated with the use of broad-spectrum antibiotics and result in an exuberant inflammatory response, leading to nosocomial diarrhea, colitis and even death. To better understand the dynamics of mucosal immunity during C. difficile infection from initiation through expansion to resolution, we built a computational model of the mucosal immune response to the bacterium. The model was calibrated using data from a mouse model of C. difficile infection. The model demonstrates a crucial role of T helper 17 (Th17 effector responses in the colonic lamina propria and luminal commensal bacteria populations in the clearance of C. difficile and colonic pathology, whereas regulatory T (Treg cells responses are associated with the recovery phase. In addition, the production of anti-microbial peptides by inflamed epithelial cells and activated neutrophils in response to C. difficile infection inhibit the re-growth of beneficial commensal bacterial species. Computational simulations suggest that the removal of neutrophil and epithelial cell derived anti-microbial inhibitions, separately and together, on commensal bacterial regrowth promote recovery and minimize colonic inflammatory pathology. Simulation results predict a decrease in colonic inflammatory markers, such as neutrophilic influx and Th17 cells in the colonic lamina propria, and length of infection with accelerated commensal bacteria re-growth through altered anti-microbial inhibition. Computational modeling provides novel insights on the therapeutic value of repopulating the colonic microbiome and inducing regulatory mucosal immune responses during C. difficile infection. Thus, modeling mucosal immunity-gut microbiota interactions has the potential to guide the development of targeted fecal transplantation therapies in the context of precision medicine interventions.

  10. Changes in Gut and Plasma Microbiome following Exercise Challenge in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS.

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    Sanjay K Shukla

    Full Text Available Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS is a disease characterized by intense and debilitating fatigue not due to physical activity that has persisted for at least 6 months, post-exertional malaise, unrefreshing sleep, and accompanied by a number of secondary symptoms, including sore throat, memory and concentration impairment, headache, and muscle/joint pain. In patients with post-exertional malaise, significant worsening of symptoms occurs following physical exertion and exercise challenge serves as a useful method for identifying biomarkers for exertion intolerance. Evidence suggests that intestinal dysbiosis and systemic responses to gut microorganisms may play a role in the symptomology of ME/CFS. As such, we hypothesized that post-exertion worsening of ME/CFS symptoms could be due to increased bacterial translocation from the intestine into the systemic circulation. To test this hypothesis, we collected symptom reports and blood and stool samples from ten clinically characterized ME/CFS patients and ten matched healthy controls before and 15 minutes, 48 hours, and 72 hours after a maximal exercise challenge. Microbiomes of blood and stool samples were examined. Stool sample microbiomes differed between ME/CFS patients and healthy controls in the abundance of several major bacterial phyla. Following maximal exercise challenge, there was an increase in relative abundance of 6 of the 9 major bacterial phyla/genera in ME/CFS patients from baseline to 72 hours post-exercise compared to only 2 of the 9 phyla/genera in controls (p = 0.005. There was also a significant difference in clearance of specific bacterial phyla from blood following exercise with high levels of bacterial sequences maintained at 72 hours post-exercise in ME/CFS patients versus clearance in the controls. These results provide evidence for a systemic effect of an altered gut microbiome in ME/CFS patients compared to controls. Upon exercise challenge, there

  11. The gut microbiome restores intrinsic and extrinsic nerve function in germ-free mice accompanied by changes in calbindin.

    Science.gov (United States)

    McVey Neufeld, K A; Perez-Burgos, A; Mao, Y K; Bienenstock, J; Kunze, W A

    2015-05-01

    The microbiome is essential for normal myenteric intrinsic primary afferent neuron (IPAN) excitability. These neurons control gut motility and modulate gut-brain signaling by exciting extrinsic afferent fibers innervating the enteric nervous system via an IPAN to extrinsic fiber sensory synapse. We investigated effects of germ-free (GF) status and conventionalization on extrinsic sensory fiber discharge in the mesenteric nerve bundle and IPAN electrophysiology, and compared these findings with those from specific pathogen-free (SPF) mice. As we have previously shown that the IPAN calcium-dependent slow afterhyperpolarization (sAHP) is enhanced in GF mice, we also examined the expression of the calcium-binding protein calbindin in these neurons in these different animal groups. IPAN sAHP and mesenteric nerve multiunit discharge were recorded using ex vivo jejunal gut segments from SPF, GF, or conventionalized (CONV) mice. IPANs were excited by adding 5 μM TRAM-34 to the serosal superfusate. We probed for calbindin expression using immunohistochemical techniques. SPF mice had a 21% increase in mesenteric nerve multiunit firing rate and CONV mice a 41% increase when IPANs were excited by TRAM-34. For GF mice, this increase was barely detectable (2%). TRAM-34 changed sAHP area under the curve by -77 for SPF, +3 for GF, or -54% for CONV animals. Calbindin-immunopositive neurons per myenteric ganglion were 36% in SPF, 24% in GF, and 52% in CONV animals. The intact microbiome is essential for normal intrinsic and extrinsic nerve function and gut-brain signaling. © 2015 John Wiley & Sons Ltd.

  12. An Investigation of Cellulose Digesting Bacteria in the Panda Gut Microbiome

    Science.gov (United States)

    Lu, M.; Leung, F. C.

    2014-12-01

    The Giant Panda (Ailuropoda melanoleuca) diet consists primarily of bamboo leaves, stems and shoots. However, the Giant Panda lacks genes for the enzymes needed to digest cellulose, the core component of bamboo. Thus, it is hypothesized that the cellulolytic digestion necessary for maintaining the Giant Panda diet is carried out by microbial symbionts in the panda gut microbiota. Fecal microbiota is used as surrogate index for gut microbiota since the Giant Panda is listed by the World Conservation Union as a Threatened Species. Two bacterial isolates with potential cellulolytic activity were isolated from Giant Panda fecal samples and cultured on selective media CMC (carboxymethyl cellulose) agar and CMC-Congo Red agar using various methods of inoculation. After incubation, clearance zones around colonies were observed and used as qualitative assays for cellulose digestion. Polymerase chain reaction amplification of the 16S rRNA gene was completed and species identification was done based on the BLAST result of 16S rRNA sequence obtained using Sanger sequencing. Once the cellulase activity is confirmed, genomic DNA of the bacteria will be extracted and used for whole genome shotgun sequencing. Illumina next generation sequencing platform will be adopted as it yields high-throughput information, providing a better understanding of cellulose digestion and the molecular genetic pathways to renewable sources of biofuels. Researchers have identified multiple cellulose-digesting microbes in the Giant Panda gut, but few have applied such bacteria in converting cellulose into glucose to create biofuel. Cellulosic ethanol, a biofuel, is produced through the fermentation of lignocellulosic biomasses. This anaerobic process is aided by cellulose-digesting enzymes. Certain microbes, such as those present in the Giant Panda gut, can produce enzymes that cleave the glycosidic bonds of cellulose (C6H10O5) into glucose molecules (C6H12O6), which can then be fermented into ethanol

  13. Alterations in the Vaginal Microbiome by Maternal Stress Are Associated With Metabolic Reprogramming of the Offspring Gut and Brain.

    Science.gov (United States)

    Jašarević, Eldin; Howerton, Christopher L; Howard, Christopher D; Bale, Tracy L

    2015-09-01

    The neonate is exposed to the maternal vaginal microbiota during parturition, providing the primary source for normal gut colonization, host immune maturation, and metabolism. These early interactions between the host and microbiota occur during a critical window of neurodevelopment, suggesting early life as an important period of cross talk between the developing gut and brain. Because perturbations in the prenatal environment such as maternal stress increase neurodevelopmental disease risk, disruptions to the vaginal ecosystem could be a contributing factor in significant and long-term consequences for the offspring. Therefore, to examine the hypothesis that changes in the vaginal microbiome are associated with effects on the offspring gut microbiota and on the developing brain, we used genomic, proteomic and metabolomic technologies to examine outcomes in our mouse model of early prenatal stress. Multivariate modeling identified broad proteomic changes to the maternal vaginal environment that influence offspring microbiota composition and metabolic processes essential for normal neurodevelopment. Maternal stress altered proteins related to vaginal immunity and abundance of Lactobacillus, the prominent taxa in the maternal vagina. Loss of maternal vaginal Lactobacillus resulted in decreased transmission of this bacterium to offspring. Further, altered microbiota composition in the neonate gut corresponded with changes in metabolite profiles involved in energy balance, and with region- and sex-specific disruptions of amino acid profiles in the developing brain. Taken together, these results identify the vaginal microbiota as a novel factor by which maternal stress may contribute to reprogramming of the developing brain that may predispose individuals to neurodevelopmental disorders.

  14. Development and validation of a microarray for the investigation of the CAZymes encoded by the human gut microbiome.

    Directory of Open Access Journals (Sweden)

    Abdessamad El Kaoutari

    Full Text Available Distal gut bacteria play a pivotal role in the digestion of dietary polysaccharides by producing a large number of carbohydrate-active enzymes (CAZymes that the host otherwise does not produce. We report here the design of a custom microarray that we used to spot non-redundant DNA probes for more than 6,500 genes encoding glycoside hydrolases and lyases selected from 174 reference genomes from distal gut bacteria. The custom microarray was tested and validated by the hybridization of bacterial DNA extracted from the stool samples of lean, obese and anorexic individuals. Our results suggest that a microarray-based study can detect genes from low-abundance bacteria better than metagenomic-based studies. A striking example was the finding that a gene encoding a GH6-family cellulase was present in all subjects examined, whereas metagenomic studies have consistently failed to detect this gene in both human and animal gut microbiomes. In addition, an examination of eight stool samples allowed the identification of a corresponding CAZome core containing 46 families of glycoside hydrolases and polysaccharide lyases, which suggests the functional stability of the gut microbiota despite large taxonomical variations between individuals.

  15. Turning Participatory Microbiome Research into Usable Data: Lessons from the American Gut Project.

    Science.gov (United States)

    Debelius, Justine W; Vázquez-Baeza, Yoshiki; McDonald, Daniel; Xu, Zhenjiang; Wolfe, Elaine; Knight, Rob

    2016-03-01

    The role of the human microbiome is the subject of continued investigation resulting in increased understanding. However, current microbiome research has only scratched the surface of the variety of healthy microbiomes. Public participation in science through crowdsourcing and crowdfunding microbiome research provides a novel opportunity for both participants and investigators. However, turning participatory science into publishable data can be challenging. Clear communication with the participant base and among researchers can ameliorate some challenges. Three major aspects need to be considered: recruitment and ongoing interaction, sample collection, and data analysis. Usable data can be maximized through diligent participant interaction, careful survey design, and maintaining an open source pipeline. While participatory science will complement rather than replace traditional avenues, it presents new opportunities for studies in the microbiome and beyond.

  16. Turning Participatory Microbiome Research into Usable Data: Lessons from the American Gut Project

    Directory of Open Access Journals (Sweden)

    Justine W. Debelius

    2015-10-01

    Full Text Available The role of the human microbiome is the subject of continued investigation resulting in increased understanding. However, current microbiome research has only scratched the surface of the variety of healthy microbiomes. Public participation in science through crowdsourcing and crowdfunding microbiome research provides a novel opportunity for both participants and investigators. However, turning participatory science into publishable data can be challenging. Clear communication with the participant base and among researchers can ameliorate some challenges. Three major aspects need to be considered: recruitment and ongoing interaction, sample collection, and data analysis. Usable data can be maximized through diligent participant interaction, careful survey design, and maintaining an open source pipeline. While participatory science will complement rather than replace traditional avenues, it presents new opportunities for studies in the microbiome and beyond.

  17. Comparative study of the gut microbiome potentially related to milk protein in Murrah buffaloes (Bubalus bubalis) and Chinese Holstein cattle.

    Science.gov (United States)

    Zhang, Jiachao; Xu, Chuanbiao; Huo, Dongxue; Hu, Qisong; Peng, Qiannan

    2017-02-08

    Previous studies suggested a close relationship between ruminant gut microbes and the mammary gland. In this study, shotgun metagenomic sequencing was used to reveal the differences in the intestinal microbiome potentially related to milk components in Murrah buffaloes and Chinese Holstein cattle. A PCoA based on the weighted Unifrac distances showed an apparent clustering pattern in the structure of intestinal microbiota between buffalo and cattle. We could attribute the structural difference to the genera of Sutterella, Coprococcus and Dorea. A further analysis of microbial functional features revealed that the biosynthesis of amino acids (including lysine, valine, leucine and isoleucine), lipopolysaccharide biosynthesis and cofactor/vitamin biosynthesis were enriched in the buffalo. In contrast, dairy cattle had higher levels of pyruvate metabolism and carbon fixation in photosynthetic organisms. A further correlation analysis based on different milk components and the typical microbiome uncovered a significant positive correlation between milk protein and the microbial biosynthesis of amino acids, which was also positively correlated in the genera of Parabacteroides, Dorea and Sutterella. This study will expand our understanding of the intestinal microbiome of buffalo and cattle as representative ruminants, as well as provide new views about how to improve the production and nutritional qualities of animal milk.

  18. Towards an Integrative Understanding of tRNA Aminoacylation–Diet–Host–Gut Microbiome Interactions in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Elena L. Paley

    2018-03-01

    Full Text Available Transgenic mice used for Alzheimer’s disease (AD preclinical experiments do not recapitulate the human disease. In our models, the dietary tryptophan metabolite tryptamine produced by human gut microbiome induces tryptophanyl-tRNA synthetase (TrpRS deficiency with consequent neurodegeneration in cells and mice. Dietary supplements, antibiotics and certain drugs increase tryptamine content in vivo. TrpRS catalyzes tryptophan attachment to tRNAtrp at initial step of protein biosynthesis. Tryptamine that easily crosses the blood–brain barrier induces vasculopathies, neurodegeneration and cell death via TrpRS competitive inhibition. TrpRS inhibitor tryptophanol produced by gut microbiome also induces neurodegeneration. TrpRS inhibition by tryptamine and its metabolites preventing tryptophan incorporation into proteins lead to protein biosynthesis impairment. Tryptophan, a least amino acid in food and proteins that cannot be synthesized by humans competes with frequent amino acids for the transport from blood to brain. Tryptophan is a vulnerable amino acid, which can be easily lost to protein biosynthesis. Some proteins marking neurodegenerative pathology, such as tau lack tryptophan. TrpRS exists in cytoplasmic (WARS and mitochondrial (WARS2 forms. Pathogenic gene variants of both forms cause TrpRS deficiency with consequent intellectual and motor disabilities in humans. The diminished tryptophan-dependent protein biosynthesis in AD patients is a proof of our model-based disease concept.

  19. Towards an Integrative Understanding of tRNA Aminoacylation-Diet-Host-Gut Microbiome Interactions in Neurodegeneration.

    Science.gov (United States)

    Paley, Elena L; Perry, George

    2018-03-26

    Transgenic mice used for Alzheimer's disease (AD) preclinical experiments do not recapitulate the human disease. In our models, the dietary tryptophan metabolite tryptamine produced by human gut microbiome induces tryptophanyl-tRNA synthetase (TrpRS) deficiency with consequent neurodegeneration in cells and mice. Dietary supplements, antibiotics and certain drugs increase tryptamine content in vivo. TrpRS catalyzes tryptophan attachment to tRNA trp at initial step of protein biosynthesis. Tryptamine that easily crosses the blood-brain barrier induces vasculopathies, neurodegeneration and cell death via TrpRS competitive inhibition. TrpRS inhibitor tryptophanol produced by gut microbiome also induces neurodegeneration. TrpRS inhibition by tryptamine and its metabolites preventing tryptophan incorporation into proteins lead to protein biosynthesis impairment. Tryptophan, a least amino acid in food and proteins that cannot be synthesized by humans competes with frequent amino acids for the transport from blood to brain. Tryptophan is a vulnerable amino acid, which can be easily lost to protein biosynthesis. Some proteins marking neurodegenerative pathology, such as tau lack tryptophan. TrpRS exists in cytoplasmic (WARS) and mitochondrial (WARS2) forms. Pathogenic gene variants of both forms cause TrpRS deficiency with consequent intellectual and motor disabilities in humans. The diminished tryptophan-dependent protein biosynthesis in AD patients is a proof of our model-based disease concept.

  20. The Overarching Influence of the Gut Microbiome on End-Organ Function: The Role of Live Probiotic Cultures

    Directory of Open Access Journals (Sweden)

    Luis Vitetta

    2014-09-01

    Full Text Available At the time of birth, humans experience an induced pro-inflammatory beneficial event. The mediators of this encouraged activity, is a fleet of bacteria that assault all mucosal surfaces as well as the skin. Thus initiating effects that eventually provide the infant with immune tissue maturation. These effects occur beneath an emergent immune system surveillance and antigenic tolerance capability radar. Over time, continuous and regulated interactions with environmental as well as commensal microbial, viral, and other antigens lead to an adapted and maintained symbiotic state of tolerance, especially in the gastrointestinal tract (GIT the organ site of the largest microbial biomass. However, the perplexing and much debated surprise has been that all microbes need not be targeted for destruction. The advent of sophisticated genomic techniques has led to microbiome studies that have begun to clarify the critical and important biochemical activities that commensal bacteria provide to ensure continued GIT homeostasis. Until recently, the GIT and its associated micro-biometabolome was a neglected factor in chronic disease development and end organ function. A systematic underestimation has been to undervalue the contribution of a persistent GIT dysbiotic (a gut barrier associated abnormality state. Dysbiosis provides a plausible clue as to the origin of systemic metabolic disorders encountered in clinical practice that may explain the epidemic of chronic diseases. Here we further build a hypothesis that posits the role that subtle adverse responses by the GIT microbiome may have in chronic diseases. Environmentally/nutritionally/and gut derived triggers can maintain microbiome perturbations that drive an abnormal overload of dysbiosis. Live probiotic cultures with specific metabolic properties may assist the GIT microbiota and reduce the local metabolic dysfunctions. As such the effect may translate to a useful clinical treatment approach for patients

  1. Beneficial Effects of a Dietary Weight Loss Intervention on Human Gut Microbiome Diversity and Metabolism Are Not Sustained during Weight Maintenance.

    Science.gov (United States)

    Heinsen, Femke-Anouska; Fangmann, Daniela; Müller, Nike; Schulte, Dominik M; Rühlemann, Malte C; Türk, Kathrin; Settgast, Ute; Lieb, Wolfgang; Baines, John F; Schreiber, Stefan; Franke, Andre; Laudes, Matthias

    2016-01-01

    In the present study, we examined the effect of a very low-calorie diet(VLCD)-based obesity program on human gut microbiome diversity and metabolism during weight loss and weight maintenance. Obese subjects underwent 3 months of VLCD followed by 3 months of weight maintenance. A lean and an obese control group were included. The microbiome was characterized by performing high-throughput dual-indexed 16S rDNA amplicon sequencing. At baseline, a significant difference in the Firmicutes/Bacteroidetes ratio between the lean and obese individuals was observed (p = 0.047). The VLCD resulted in significant alterations in gut microbiome diversity from baseline to 3 months (p = 0.0053). Acinetobacter represented an indicator species for the observed effect (indicator value = 0.998, p = 0.006). Metabolic analyses revealed alterations of the bacterial riboflavin pathway from baseline to 3 months (pnom = 0.0078). These changes in diversity and bacterial metabolism induced by VLCD diminished during the weight maintenance phase, despite sustained reductions in body weight and sustained improvements of insulin sensitivity. The present data show that a VLCD is able to beneficially alter both gut microbiome diversity and metabolism in obese humans, but that these changes are not sustained during weight maintenance. This finding might suggest that the microbiome should be targeted during obesity programs. © 2016 The Author(s) Published by S. Karger GmbH, Freiburg.

  2. Beneficial Effects of a Dietary Weight Loss Intervention on Human Gut Microbiome Diversity and Metabolism Are Not Sustained during Weight Maintenance

    Directory of Open Access Journals (Sweden)

    Femke-Anouska Heinsen

    2016-11-01

    Full Text Available Objective: In the present study, we examined the effect of a very low-calorie diet(VLCD-based obesity program on human gut microbiome diversity and metabolism during weight loss and weight maintenance. Methods: Obese subjects underwent 3 months of VLCD followed by 3 months of weight maintenance. A lean and an obese control group were included. The microbiome was characterized by performing high-throughput dual-indexed 16S rDNA amplicon sequencing. Results: At baseline, a significant difference in the Firmicutes/Bacteroidetes ratio between the lean and obese individuals was observed (p = 0.047. The VLCD resulted in significant alterations in gut microbiome diversity from baseline to 3 months (p = 0.0053. Acinetobacter represented an indicator species for the observed effect (indicator value = 0.998, p = 0.006. Metabolic analyses revealed alterations of the bacterial riboflavin pathway from baseline to 3 months (pnom = 0.0078. These changes in diversity and bacterial metabolism induced by VLCD diminished during the weight maintenance phase, despite sustained reductions in body weight and sustained improvements of insulin sensitivity. Conclusion: The present data show that a VLCD is able to beneficially alter both gut microbiome diversity and metabolism in obese humans, but that these changes are not sustained during weight maintenance. This finding might suggest that the microbiome should be targeted during obesity programs.

  3. Changes in Composition of the Gut Bacterial Microbiome after Fecal Microbiota Transplantation for Recurrent Clostridium difficile Infection in a Pediatric Heart Transplant Patient.

    Science.gov (United States)

    Flannigan, Kyle L; Rajbar, Taylor; Moffat, Andrew; McKenzie, Leanna S; Dicke, Frank; Rioux, Kevin; Workentine, Matthew L; Louie, Thomas J; Hirota, Simon A; Greenway, Steven C

    2017-01-01

    The microbiome is increasingly recognized as an important influence on human health and many of the comorbidities that affect patients after solid organ transplantation (SOT) have been shown to involve changes in gut bacterial populations. Thus, microbiome changes in an individual patient may have important health implications after SOT but this area remains understudied. We describe changes in the composition of the fecal microbiome from a pediatric heart transplant recipient before and >2.5 years after he underwent repeated fecal microbiota transplantation (FMT) for recurrent Clostridium difficile infection (CDI). With both documented episodes of CDI, there was marked loss of bacterial diversity with overgrowth of Proteobacteria (>98.9% of phyla identified) associated with symptomatic colitis that was corrected after FMT. We hypothesize that a second CDI occurring after FMT was related to incomplete restoration of normal bowel flora post-FMT with relative deficiencies of the phyla Firmicutes and Bacteroidetes and the families Lachnospiraceae and Ruminococcaceae . Following the second FMT, there was a gradual shift in gut bacterial composition coincident with the recipient developing lymphonodular hyperplasia of the colon and painless hematochezia that resolved with discontinuation of mycophenolate mofetil (MMF). This case documents dynamic changes in the bacterial microbiome after FMT and suggests that MMF may influence the gut microbiome with consequences for the patient.

  4. Significant Correlation Between the Infant Gut Microbiome and Rotavirus Vaccine Response in Rural Ghana.

    Science.gov (United States)

    Harris, Vanessa C; Armah, George; Fuentes, Susana; Korpela, Katri E; Parashar, Umesh; Victor, John C; Tate, Jacqueline; de Weerth, Carolina; Giaquinto, Carlo; Wiersinga, Willem Joost; Lewis, Kristen D C; de Vos, Willem M

    2017-01-01

     Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and 95% of RV-associated deaths occur in Africa and Asia where RV vaccines (RVVs) have lower efficacy. We hypothesize that differences in intestinal microbiome composition correlate with the decreased RVV efficacy observed in poor settings.  We conducted a nested, case-control study comparing prevaccination, fecal microbiome compositions between 6-week old, matched RVV responders and nonresponders in rural Ghana. These infants' microbiomes were then compared with 154 age-matched, healthy Dutch infants' microbiomes, assumed to be RVV responders. Fecal microbiome analysis was performed in all groups using the Human Intestinal Tract Chip.  We analyzed findings in 78 Ghanaian infants, including 39 RVV responder and nonresponder pairs. The overall microbiome composition was significantly different between RVV responders and nonresponders (FDR, 0.12), and Ghanaian responders were more similar to Dutch infants than nonresponders (P = .002). RVV response correlated with an increased abundance of Streptococcus bovis and a decreased abundance of the Bacteroidetes phylum in comparisons between both Ghanaian RVV responders and nonresponders (FDR, 0.008 vs 0.003) and Dutch infants and Ghanaian nonresponders (FDR, 0.002 vs 0.009).  The intestinal microbiome composition correlates significantly with RVV immunogenicity and may contribute to the diminished RVV immunogenicity observed in developing countries. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  5. Effects of the Dietary Protein and Carbohydrate Ratio on Gut Microbiomes in Dogs of Different Body Conditions.

    Science.gov (United States)

    Li, Qinghong; Lauber, Christian L; Czarnecki-Maulden, Gail; Pan, Yuanlong; Hannah, Steven S

    2017-01-24

    Obesity has become a health epidemic in both humans and pets. A dysbiotic gut microbiota has been associated with obesity and other metabolic disorders. High-protein, low-carbohydrate (HPLC) diets have been recommended for body weight loss, but little is known about their effects on the canine gut microbiome. Sixty-three obese and lean Labrador retrievers and Beagles (mean age, 5.72 years) were fed a common baseline diet for 4 weeks in phase 1, followed by 4 weeks of a treatment diet, specifically, the HPLC diet (49.4% protein, 10.9% carbohydrate) or a low-protein, high-carbohydrate (LPHC) diet (25.5% protein, 38.8% carbohydrate) in phase 2. 16S rRNA gene profiling revealed that dietary protein and carbohydrate ratios have significant impacts on gut microbial compositions. This effect appeared to be more evident in obese dogs than in lean dogs but was independent of breed. Consumption of either diet increased the bacterial evenness, but not the richness, of the gut compared to that after consumption of the baseline diet. Macronutrient composition affected taxon abundances, mainly within the predominant phyla, Firmicutes and Bacteroidetes The LPHC diet appeared to favor the growth of Bacteroides uniformis and Clostridium butyricum, while the HPLC diet increased the abundances of Clostridium hiranonis, Clostridium perfringens, and Ruminococcus gnavus and enriched microbial gene networks associated with weight maintenance. In addition, we observed a decrease in the Bacteroidetes to Firmicutes ratio and an increase in the Bacteroides to Prevotella ratio in the HPLC diet-fed dogs compared to these ratios in dogs fed other diets. Finally, analysis of the effect of diet on the predicted microbial gene network was performed using phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). More than 50% of dogs are either overweight or obese in the United States. A dysbiotic gut microbiota is associated with obesity and other

  6. Oligotyping reveals differences between gut microbiomes of free-ranging sympatric Namibian carnivores (Acinonyx jubatus, Canis mesomelas) on a bacterial species-like level

    Czech Academy of Sciences Publication Activity Database

    Menke, S.; Wasimuddin, Wasimuddin; Meier, M.; Melzheimer, J.; Mfune, J. K. E.; Heinrich, S.; Thalwitzer, S.; Wachter, B.; Sommer, S.

    2014-01-01

    Roč. 5, č. 526 (2014), s. 526 ISSN 1664-302X R&D Projects: GA MŠk EE2.3.20.0303 Institutional support: RVO:68081766 Keywords : gut microbiome * bacteria * oligotyping * carnivores * cheetah (Acinonyx jubatus) * black-backed jackal (Canis mesomelas) * Namibia Subject RIV: EG - Zoology Impact factor: 3.989, year: 2014

  7. Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial.

    Science.gov (United States)

    Villar-García, Judit; Güerri-Fernández, Robert; Moya, Andrés; González, Alicia; Hernández, Juan J; Lerma, Elisabet; Guelar, Ana; Sorli, Luisa; Horcajada, Juan P; Artacho, Alejandro; D Auria, Giuseppe; Knobel, Hernando

    2017-01-01

    Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly reduced plasma levels of bacterial translocation (Lipopolysaccharide-binding protein or LBP) and systemic inflammation (IL-6) in 44 HIV virologically suppressed patients, half of whom (n = 22) had immunologic non-response to antiretroviral therapy (Saccharomyces boulardii is due to modified gut microbiome composition, with a decrease of some species associated with higher systemic levels of microbial translocation and inflammation. In this study, we used 16S rDNA gene amplification and parallel sequencing to analyze the probiotic impact on the composition of the gut microbiome (faecal samples) in these 44 patients randomized to receive oral supplementation with probiotic or placebo for 12 weeks. Compared to the placebo group, in individuals treated with probiotic we observed lower concentrations of some gut species, such as those of the Clostridiaceae family, which were correlated with systemic levels of bacterial translocation and inflammation markers. In a sub-study of these patients, we observed significantly higher parameters of microbial translocation (LBP, soluble CD14) and systemic inflammation in immunologic non-responders than in immunologic responders, which was correlated with a relative abundance of specific gut bacterial groups (Lachnospiraceae genus and Proteobacteria). Thus, in this work, we propose a new therapeutic strategy using the probiotic yeast S. boulardii to modify gut microbiome composition. Identifying pro-inflammatory species in the gut microbiome

  8. Microbiome-Gut-Brain Axis: A Pathway for Improving Brainstem Serotonin Homeostasis and Successful Autoresuscitation in SIDS-A Novel Hypothesis.

    Science.gov (United States)

    Praveen, Vijayakumar; Praveen, Shama

    2016-01-01

    Sudden infant death syndrome (SIDS) continues to be a major public health issue. Following its major decline since the "Back to Sleep" campaign, the incidence of SIDS has plateaued, with an annual incidence of about 1,500 SIDS-related deaths in the United States and thousands more throughout the world. The etiology of SIDS, the major cause of postneonatal mortality in the western world, is still poorly understood. Although sleeping in prone position is a major risk factor, SIDS continues to occur even in the supine sleeping position. The triple-risk model of Filiano and Kinney emphasizes the interaction between a susceptible infant during a critical developmental period and stressor/s in the pathogenesis of SIDS. Recent evidence ranges from dysregulated autonomic control to findings of altered neurochemistry, especially the serotonergic system that plays an important role in brainstem cardiorespiratory/thermoregulatory centers. Brainstem serotonin (5-HT) and tryptophan hydroxylase-2 (TPH-2) levels have been shown to be lower in SIDS, supporting the evidence that defects in the medullary serotonergic system play a significant role in SIDS. Pathogenic bacteria and their enterotoxins have been associated with SIDS, although no direct evidence has been established. We present a new hypothesis that the infant's gut microbiome, and/or its metabolites, by its direct effects on the gut enterochromaffin cells, stimulates the afferent gut vagal endings by releasing serotonin (paracrine effect), optimizing autoresuscitation by modulating brainstem 5-HT levels through the microbiome-gut-brain axis, thus playing a significant role in SIDS during the critical period of gut flora development and vulnerability to SIDS. The shared similarities between various risk factors for SIDS and their relationship with the infant gut microbiome support our hypothesis. Comprehensive gut-microbiome studies are required to test our hypothesis.

  9. Diet, Gut Microbiome and Epigenetics: Emerging Links with Inflammatory Bowel Diseases and Prospects for Management and Prevention.

    Science.gov (United States)

    Aleksandrova, Krasimira; Romero-Mosquera, Beatriz; Hernandez, Vicent

    2017-08-30

    Inflammatory bowel diseases (IBD) represent a growing public health concern due to increasing incidence worldwide. The current notion on the pathogenesis of IBD is that genetically susceptible individuals develop intolerance to dysregulated gut microflora (dysbiosis) and chronic inflammation develops as a result of environmental triggers. Among the environmental factors associated with IBD, diet plays an important role in modulating the gut microbiome, influencing epigenetic changes, and, therefore, could be applied as a therapeutic tool to improve the disease course. Nevertheless, the current dietary recommendations for disease prevention and management are scarce and have weak evidence. This review summarises the current knowledge on the complex interactions between diet, microbiome and epigenetics in IBD. Whereas an overabundance of calories and some macronutrients increase gut inflammation, several micronutrients have the potential to modulate it. Immunonutrition has emerged as a new concept putting forward the importance of vitamins such as vitamins A, C, E, and D, folic acid, beta carotene and trace elements such as zinc, selenium, manganese and iron. However, when assessed in clinical trials, specific micronutrients exerted a limited benefit. Beyond nutrients, an anti-inflammatory dietary pattern as a complex intervention approach has become popular in recent years. Hence, exclusive enteral nutrition in paediatric Crohn's disease is the only nutritional intervention currently recommended as a first-line therapy. Other nutritional interventions or specific diets including the Specific Carbohydrate Diet (SCD), the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyol (FODMAP) diet and, most recently, the Mediterranean diet have shown strong anti-inflammatory properties and show promise for improving disease symptoms. More work is required to evaluate the role of individual food compounds and complex nutritional interventions with the

  10. Trypanosome infection establishment in the tsetse fly gut is influenced by microbiome-regulated host immune barriers.

    Directory of Open Access Journals (Sweden)

    Brian L Weiss

    Full Text Available Tsetse flies (Glossina spp. vector pathogenic African trypanosomes, which cause sleeping sickness in humans and nagana in domesticated animals. Additionally, tsetse harbors 3 maternally transmitted endosymbiotic bacteria that modulate their host's physiology. Tsetse is highly resistant to infection with trypanosomes, and this phenotype depends on multiple physiological factors at the time of challenge. These factors include host age, density of maternally-derived trypanolytic effector molecules present in the gut, and symbiont status during development. In this study, we investigated the molecular mechanisms that result in tsetse's resistance to trypanosomes. We found that following parasite challenge, young susceptible tsetse present a highly attenuated immune response. In contrast, mature refractory flies express higher levels of genes associated with humoral (attacin and pgrp-lb and epithelial (inducible nitric oxide synthase and dual oxidase immunity. Additionally, we discovered that tsetse must harbor its endogenous microbiome during intrauterine larval development in order to present a parasite refractory phenotype during adulthood. Interestingly, mature aposymbiotic flies (Gmm(Apo present a strong immune response earlier in the infection process than do WT flies that harbor symbiotic bacteria throughout their entire lifecycle. However, this early response fails to confer significant resistance to trypanosomes. Gmm(Apo adults present a structurally compromised peritrophic matrix (PM, which lines the fly midgut and serves as a physical barrier that separates luminal contents from immune responsive epithelial cells. We propose that the early immune response we observe in Gmm(Apo flies following parasite challenge results from the premature exposure of gut epithelia to parasite-derived immunogens in the absence of a robust PM. Thus, tsetse's PM appears to regulate the timing of host immune induction following parasite challenge. Our results

  11. Interactions between host genetics and gut microbiome in diabetes and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Siegfried Ussar

    2016-09-01

    Major conclusions: Understanding these complex interactions will help in the development of novel treatments for microbiome-related metabolic diseases. This article is part of a special issue on microbiota.

  12. Whole gut microbiome composition of damselfish and cardinalfish before and after reef settlement

    OpenAIRE

    Parris, Darren J.; Brooker, Rohan M.; Morgan, Michael A.; Dixson, Danielle L.; Stewart, Frank J.

    2016-01-01

    The Pomacentridae (damselfish) and Apogonidae (cardinalfish) are among the most common fish families on coral reefs and in the aquarium trade. Members of both families undergo a pelagic larvae phase prior to settlement on the reef, where adults play key roles in benthic habitat structuring and trophic interactions. Fish-associated microbial communities (microbiomes) significantly influence fish health and ecology, yet little is known of how microbiomes change with life stage. We quantified th...

  13. A Prospective Metagenomic and Metabolomic Analysis of the Impact of Exercise and/or Whey Protein Supplementation on the Gut Microbiome of Sedentary Adults.

    Science.gov (United States)

    Cronin, Owen; Barton, Wiley; Skuse, Peter; Penney, Nicholas C; Garcia-Perez, Isabel; Murphy, Eileen F; Woods, Trevor; Nugent, Helena; Fanning, Aine; Melgar, Silvia; Falvey, Eanna C; Holmes, Elaine; Cotter, Paul D; O'Sullivan, Orla; Molloy, Michael G; Shanahan, Fergus

    2018-01-01

    Many components of modern living exert influence on the resident intestinal microbiota of humans with resultant impact on host health. For example, exercise-associated changes in the diversity, composition, and functional profiles of microbial populations in the gut have been described in cross-sectional studies of habitual athletes. However, this relationship is also affected by changes in diet, such as changes in dietary and supplementary protein consumption, that coincide with exercise. To determine whether increasing physical activity and/or increased protein intake modulates gut microbial composition and function, we prospectively challenged healthy but sedentary adults with a short-term exercise regime, with and without concurrent daily whey protein consumption. Metagenomics- and metabolomics-based assessments demonstrated modest changes in gut microbial composition and function following increases in physical activity. Significant changes in the diversity of the gut virome were evident in participants receiving daily whey protein supplementation. Results indicate that improved body composition with exercise is not dependent on major changes in the diversity of microbial populations in the gut. The diverse microbial characteristics previously observed in long-term habitual athletes may be a later response to exercise and fitness improvement. IMPORTANCE The gut microbiota of humans is a critical component of functional development and subsequent health. It is important to understand the lifestyle and dietary factors that affect the gut microbiome and what impact these factors may have. Animal studies suggest that exercise can directly affect the gut microbiota, and elite athletes demonstrate unique beneficial and diverse gut microbiome characteristics. These characteristics are associated with levels of protein consumption and levels of physical activity. The results of this study show that increasing the fitness levels of physically inactive humans leads to

  14. Roux-en-Y Gastric Bypass and Vertical Banded Gastroplasty Induce Long-Term Changes on the Human Gut Microbiome Contributing to Fat Mass Regulation

    DEFF Research Database (Denmark)

    Tremaroli, Valentina; Karlsson, Fredrik; Werling, Malin

    2015-01-01

    Bariatric surgery is currently the most effective procedure for the treatment of obesity. Given the role of the gut microbiota in regulating host metabolism and adiposity, we investigated the long-term effects of bariatric surgery on the microbiome of patients randomized to Roux-en-Y gastric bypass...... or vertical banded gastroplasty and matched for weight and fat mass loss. The two surgical procedures induced similar and durable changes on the gut microbiome that were not dependent on body mass index and resulted in altered levels of fecal and circulating metabolites compared with obese controls....... By colonizing germ-free mice with stools from the patients, we demonstrated that the surgically altered microbiota promoted reduced fat deposition in recipient mice. These mice also had a lower respiratory quotient, indicating decreased utilization of carbohydrates as fuel. Our results suggest that the gut...

  15. Seasonal, spatial, and maternal effects on gut microbiome in wild red squirrels.

    Science.gov (United States)

    Ren, Tiantian; Boutin, Stan; Humphries, Murray M; Dantzer, Ben; Gorrell, Jamieson C; Coltman, David W; McAdam, Andrew G; Wu, Martin

    2017-12-21

    Our understanding of gut microbiota has been limited primarily to findings from human and laboratory animals, but what shapes the gut microbiota in nature remains largely unknown. To fill this gap, we conducted a comprehensive study of gut microbiota of a well-studied North American red squirrel (Tamiasciurus hudsonicus) population. Red squirrels are territorial, solitary, and live in a highly seasonal environment and therefore represent a very attractive system to study factors that drive the temporal and spatial dynamics of gut microbiota. For the first time, this study revealed significant spatial patterns of gut microbiota within a host population, suggesting limited dispersal could play a role in shaping and maintaining the structure of gut microbial communities. We also found a remarkable seasonal rhythm in red squirrel's gut microbial composition manifested by a tradeoff between relative abundance of two genera Oscillospira and Corpococcus and clearly associated with seasonal variation in diet availability. Our results show that in nature, environmental factors exert a much stronger influence on gut microbiota than host-associated factors including age and sex. Despite strong environmental effects, we found clear evidence of individuality and maternal effects, but host genetics did not seem to be a significant driver of the gut microbial communities in red squirrels. Taken together, the results of this study emphasize the importance of external ecological factors rather than host attributes in driving temporal and spatial patterns of gut microbiota in natural environment.

  16. Exercise Prevents Enhanced Postoperative Neuroinflammation and Cognitive Decline and Rectifies the Gut Microbiome in a Rat Model of Metabolic Syndrome.

    Science.gov (United States)

    Feng, Xiaomei; Uchida, Yosuke; Koch, Lauren; Britton, Steve; Hu, Jun; Lutrin, David; Maze, Mervyn

    2017-01-01

    Postoperative cognitive decline (PCD) can affect in excess of 10% of surgical patients and can be considerably higher with risk factors including advanced age, perioperative infection, and metabolic conditions such as obesity and insulin resistance. To define underlying pathophysiologic processes, we used animal models including a rat model of metabolic syndrome generated by breeding for a trait of low aerobic exercise tolerance. After 35 generations, the low capacity runner (LCR) rats differ 10-fold in their aerobic exercise capacity from high capacity runner (HCR) rats. The LCR rats respond to surgical procedure with an abnormal phenotype consisting of exaggerated and persistent PCD and failure to resolve neuroinflammation. We determined whether preoperative exercise can rectify the abnormal surgical phenotype. Following institutional approval of the protocol each of male LCR and male HCR rats were randomly assigned to four groups and subjected to isoflurane anesthesia and tibia fracture with internal fixation (surgery) or anesthesia alone (sham surgery) and to a preoperative exercise regimen that involved walking for 10 km on a treadmill over 6 weeks (exercise) or being placed on a stationary treadmill (no exercise). Feces were collected before and after exercise for assessment of gut microbiome. Three days following surgery or sham surgery the rats were tested for ability to recall a contextual aversive stimulus in a trace fear conditioning paradigm. Thereafter some rats were euthanized and the hippocampus harvested for analysis of inflammatory mediators. At 3 months, the remainder of the rats were tested for memory recall by the probe test in a Morris Water Maze. Postoperatively, LCR rats exhibited exaggerated cognitive decline both at 3 days and at 3 months that was prevented by preoperative exercise. Similarly, LCR rats had excessive postoperative neuroinflammation that was normalized by preoperative exercise. Diversity of the gut microbiome in the

  17. A review of metabolic potential of human gut microbiome in human nutrition.

    Science.gov (United States)

    Yadav, Monika; Verma, Manoj Kumar; Chauhan, Nar Singh

    2018-03-01

    The human gut contains a plethora of microbes, providing a platform for metabolic interaction between the host and microbiota. Metabolites produced by the gut microbiota act as a link between gut microbiota and its host. These metabolites act as messengers having the capacity to alter the gut microbiota. Recent advances in the characterization of the gut microbiota and its symbiotic relationship with the host have provided a platform to decode metabolic interactions. The human gut microbiota, a crucial component for dietary metabolism, is shaped by the genetic, epigenetic and dietary factors. The metabolic potential of gut microbiota explains its significance in host health and diseases. The knowledge of interactions between microbiota and host metabolism, as well as modification of microbial ecology, is really beneficial to have effective therapeutic treatments for many diet-related diseases in near future. This review cumulates the information to map the role of human gut microbiota in dietary component metabolism, the role of gut microbes derived metabolites in human health and host-microbe metabolic interactions in health and diseases.

  18. Metagenomic Analysis of the Gut Microbiome of the Common Black Slug Arion ater in Search of Novel Lignocellulose Degrading Enzymes

    Directory of Open Access Journals (Sweden)

    Ryan Joynson

    2017-11-01

    Full Text Available Some eukaryotes are able to gain access to well-protected carbon sources in plant biomass by exploiting microorganisms in the environment or harbored in their digestive system. One is the land pulmonate Arion ater, which takes advantage of a gut microbial consortium that can break down the widely available, but difficult to digest, carbohydrate polymers in lignocellulose, enabling them to digest a broad range of fresh and partially degraded plant material efficiently. This ability is considered one of the major factors that have enabled A. ater to become one of the most widespread plant pest species in Western Europe and North America. Using metagenomic techniques we have characterized the bacterial diversity and functional capability of the gut microbiome of this notorious agricultural pest. Analysis of gut metagenomic community sequences identified abundant populations of known lignocellulose-degrading bacteria, along with well-characterized bacterial plant pathogens. This also revealed a repertoire of more than 3,383 carbohydrate active enzymes (CAZymes including multiple enzymes associated with lignin degradation, demonstrating a microbial consortium capable of degradation of all components of lignocellulose. This would allow A. ater to make extensive use of plant biomass as a source of nutrients through exploitation of the enzymatic capabilities of the gut microbial consortia. From this metagenome assembly we also demonstrate the successful amplification of multiple predicted gene sequences from metagenomic DNA subjected to whole genome amplification and expression of functional proteins, facilitating the low cost acquisition and biochemical testing of the many thousands of novel genes identified in metagenomics studies. These findings demonstrate the importance of studying Gastropod microbial communities. Firstly, with respect to understanding links between feeding and evolutionary success and, secondly, as sources of novel enzymes with

  19. Effects of the Dietary Protein and Carbohydrate Ratio on Gut Microbiomes in Dogs of Different Body Conditions

    Directory of Open Access Journals (Sweden)

    Qinghong Li

    2017-01-01

    Full Text Available Obesity has become a health epidemic in both humans and pets. A dysbiotic gut microbiota has been associated with obesity and other metabolic disorders. High-protein, low-carbohydrate (HPLC diets have been recommended for body weight loss, but little is known about their effects on the canine gut microbiome. Sixty-three obese and lean Labrador retrievers and Beagles (mean age, 5.72 years were fed a common baseline diet for 4 weeks in phase 1, followed by 4 weeks of a treatment diet, specifically, the HPLC diet (49.4% protein, 10.9% carbohydrate or a low-protein, high-carbohydrate (LPHC diet (25.5% protein, 38.8% carbohydrate in phase 2. 16S rRNA gene profiling revealed that dietary protein and carbohydrate ratios have significant impacts on gut microbial compositions. This effect appeared to be more evident in obese dogs than in lean dogs but was independent of breed. Consumption of either diet increased the bacterial evenness, but not the richness, of the gut compared to that after consumption of the baseline diet. Macronutrient composition affected taxon abundances, mainly within the predominant phyla, Firmicutes and Bacteroidetes. The LPHC diet appeared to favor the growth of Bacteroides uniformis and Clostridium butyricum, while the HPLC diet increased the abundances of Clostridium hiranonis, Clostridium perfringens, and Ruminococcus gnavus and enriched microbial gene networks associated with weight maintenance. In addition, we observed a decrease in the Bacteroidetes to Firmicutes ratio and an increase in the Bacteroides to Prevotella ratio in the HPLC diet-fed dogs compared to these ratios in dogs fed other diets. Finally, analysis of the effect of diet on the predicted microbial gene network was performed using phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt.

  20. Fast acquisition of a polysaccharide fermenting gut microbiome by juvenile green turtles Chelonia mydas after settlement in coastal habitats.

    Science.gov (United States)

    Campos, Patricia; Guivernau, Miriam; Prenafeta-Boldú, Francesc X; Cardona, Luis

    2018-04-10

    Tetrapods do not express hydrolases for cellulose and hemicellulose assimilation, and hence, the independent acquisition of herbivory required the establishment of new endosymbiotic relationships between tetrapods and microbes. Green turtles (Chelonia mydas) are one of the three groups of marine tetrapods with an herbivorous diet and which acquire it after several years consuming pelagic animals. We characterized the microbiota present in the feces and rectum of 24 young wild and captive green turtles from the coastal waters of Brazil, with curved carapace length ranging from 31.1 to 64.7 cm, to test the hypotheses that (1) the ontogenetic dietary shift after settlement is followed by a gradual change in the composition and diversity of the gut microbiome, (2) differences exist between the composition and diversity of the gut microbiome of green turtles from tropical and subtropical regions, and (3) the consumption of omnivorous diets modifies the gut microbiota of green turtles. A genomic library of 2,186,596 valid bacterial 16S rRNA reads was obtained and these sequences were grouped into 6321 different operational taxonomic units (at 97% sequence homology cutoff). The results indicated that most of the juvenile green turtles less than 45 cm of curved carapace length exhibited a fecal microbiota co-dominated by representatives of the phyla Bacteroidetes and Firmicutes and high levels of Clostridiaceae, Prophyromonas, Ruminococaceae, and Lachnospiraceae within the latter phylum. Furthermore, this was the only microbiota profile found in wild green turtles > 45 cm CCL and in most of the captive green turtles of any size feeding on a macroalgae/fish mixed diet. Nevertheless, microbial diversity increased with turtle size and was higher in turtles from tropical than from subtropical regions. These results indicate that juvenile green turtles from the coastal waters of Brazil had the same general microbiota, regardless of body size and origin, and suggest a fast

  1. Restructuring of the Gut Microbiome by Intermittent Fasting Prevents Retinopathy and Prolongs Survival in db/db Mice.

    Science.gov (United States)

    Beli, Eleni; Yan, Yuanqing; Moldovan, Leni; Vieira, Cristiano P; Gao, Ruli; Duan, Yaqian; Prasad, Ram; Bhatwadekar, Ashay; White, Fletcher A; Townsend, Steven; Chan, Luisa; Ryan, Caitlin N; Morton, Daniel; Moldovan, Emil G; Chu, Fang-I; Oudit, Gavin Y; Derendorf, Hartmut; Adorini, Luciano; Wang, Xiaoxin X; Evans-Molina, Carmella; Mirmira, Raghavendra G; Boulton, Michael E; Yoder, Mervin C; Li, Qiuhong; Levi, Moshe; Busik, Julia V; Grant, Maria B

    2018-04-30

    Intermittent fasting (IF) protects against the development of metabolic diseases and cancer, but whether it can prevent diabetic microvascular complications is not known. In db/db mice, we examined the impact of long-term IF on diabetic retinopathy (DR). Despite no change in glycated hemoglobin, db/db mice on the IF regimen displayed significantly longer survival and a reduction in DR endpoints, including acellular capillaries and leukocyte infiltration. We hypothesized that IF mediated changes in the gut microbiota would produce beneficial metabolites and prevent the development of DR. Microbiome analysis revealed increased levels of Firmicutes and decreased Bacteroidetes and Verrucomicrobia Compared to db/db mice on ad-libitum (AL) feeding, changes in the microbiome of the db/db mice on IF were associated with increases in gut mucin, goblet cell number and villi length and reductions in plasma peptidoglycan. Consistent with the known modulatory effects of Firmicutes on bile acid (BA) metabolism, measurement of BAs demonstrated a significant increase of tauroursodeoxycholate (TUDCA), a neuroprotective BA, in db/db on IF but not in db/db on AL feeding. TGR-5, the TUDCA receptor, was found in neural cells of the retina primary ganglion cells. Expression of TGR5 did not change with IF or diabetes. However, IF reduced retinal TNF-α mRNA, which is a key downstream target of TGR-5 activation. Pharmacological activation of TGR5 using INT-767 prevented DR in a second diabetic mouse model. These findings support the concept that IF prevents DR by restructuring the microbiota towards species producing TUDCA and subsequent retinal protection by TGR5 activation. © 2018 by the American Diabetes Association.

  2. Gut metabolome meets microbiome: A methodological perspective to understand the relationship between host and microbe.

    Science.gov (United States)

    Lamichhane, Santosh; Sen, Partho; Dickens, Alex M; Orešič, Matej; Bertram, Hanne Christine

    2018-04-30

    It is well established that gut microbes and their metabolic products regulate host metabolism. The interactions between the host and its gut microbiota are highly dynamic and complex. In this review we present and discuss the metabolomic strategies to study the gut microbial ecosystem. We highlight the metabolic profiling approaches to study faecal samples aimed at deciphering the metabolic product derived from gut microbiota. We also discuss how metabolomics data can be integrated with metagenomics data derived from gut microbiota and how such approaches may lead to better understanding of the microbial functions. Finally, the emerging approaches of genome-scale metabolic modelling to study microbial co-metabolism and host-microbe interactions are highlighted. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Introduction to the special focus issue on the impact of diet on gut microbiota composition and function and future opportunities for nutritional modulation of the gut microbiome to improve human health.

    Science.gov (United States)

    Donovan, Sharon M

    2017-03-04

    Over the past decade, application of culture-independent, next generation DNA sequencing has dramatically enhanced our understanding of the composition of the gut microbiome and its association with human states of health and disease. Host genetics, age, and environmental factors such as where and who you live with, use of pre-, pro- and antibiotics, exercise and diet influence the short- and long-term composition of the microbiome. Dietary intake is a key determinant of microbiome composition and diversity and studies to date have linked long-term dietary patterns as well as short-term dietary interventions to the composition and diversity of the gut microbiome. The goal of this special focus issue was to review the role of diet in regulating the composition and function of the gut microbiota across the lifespan, from pregnancy to old age. Overall dietary patterns, as well as perturbations such as undernutrition and obesity, as well as the effects of dietary fiber/prebiotics and fat composition are explored.

  4. Oligotyping reveals differences between gut-microbiomes of free-ranging sympatric Namibian carnivores (Acinonyx jubatus, Canis mesomelas on a bacterial species-like level

    Directory of Open Access Journals (Sweden)

    Sebastian eMenke

    2014-10-01

    Full Text Available Recent gut microbiome studies in model organisms emphasize the effects of intrinsic and extrinsic factors on the variation of the bacterial composition and its impact on the overall health status of the host. Species occurring in the same habitat might share a similar microbiome, especially if they overlap in ecological and behavioral traits. So far, the natural variation in microbiomes of free-ranging wildlife species has not been thoroughly investigated. The few existing studies exploring microbiomes through 16S rRNA gene reads clustered sequencing reads into operational taxonomic units (OTUs based on a similarity threshold (e.g. 97%. This approach, in combination with the low resolution of target databases, generally limits the level of taxonomic assignments to the genus level. However, distinguishing natural variation of microbiomes in healthy individuals from abnormal microbial compositions that affect host health requires knowledge of the normal microbial flora at a high taxonomic resolution. This gap can now be addressed using the recently published oligotyping approach, which can resolve closely related organisms into distinct oligotypes by utilizing subtle nucleotide variation. Here, we used Illumina MiSeq to sequence amplicons generated from the V4 region of the 16S rRNA gene to investigate the gut microbiome of two free-ranging sympatric Namibian carnivore species, the cheetah (Acinonyx jubatus and the black-backed jackal (Canis mesomelas. Bacterial phyla with proportions > 0.2 % were identical for both species and included Firmicutes, Fusobacteria, Bacteroidetes, Proteobacteria and Actinobacteria. At a finer taxonomic resolution, black-backed jackals exhibited 69 bacterial taxa with proportions ≥ 0.1 %, whereas cheetahs had only 42. Finally, oligotyping revealed that shared bacterial taxa consisted of distinct oligotype profiles. Thus, in contrast to 3 % OTUs, oligotyping can detect fine-scale taxonomic differences between

  5. Oligotyping reveals differences between gut microbiomes of free-ranging sympatric Namibian carnivores (Acinonyx jubatus, Canis mesomelas) on a bacterial species-like level.

    Science.gov (United States)

    Menke, Sebastian; Wasimuddin; Meier, Matthias; Melzheimer, Jörg; Mfune, John K E; Heinrich, Sonja; Thalwitzer, Susanne; Wachter, Bettina; Sommer, Simone

    2014-01-01

    Recent gut microbiome studies in model organisms emphasize the effects of intrinsic and extrinsic factors on the variation of the bacterial composition and its impact on the overall health status of the host. Species occurring in the same habitat might share a similar microbiome, especially if they overlap in ecological and behavioral traits. So far, the natural variation in microbiomes of free-ranging wildlife species has not been thoroughly investigated. The few existing studies exploring microbiomes through 16S rRNA gene reads clustered sequencing reads into operational taxonomic units (OTUs) based on a similarity threshold (e.g., 97%). This approach, in combination with the low resolution of target databases, generally limits the level of taxonomic assignments to the genus level. However, distinguishing natural variation of microbiomes in healthy individuals from "abnormal" microbial compositions that affect host health requires knowledge of the "normal" microbial flora at a high taxonomic resolution. This gap can now be addressed using the recently published oligotyping approach, which can resolve closely related organisms into distinct oligotypes by utilizing subtle nucleotide variation. Here, we used Illumina MiSeq to sequence amplicons generated from the V4 region of the 16S rRNA gene to investigate the gut microbiome of two free-ranging sympatric Namibian carnivore species, the cheetah (Acinonyx jubatus) and the black-backed jackal (Canis mesomelas). Bacterial phyla with proportions >0.2% were identical for both species and included Firmicutes, Fusobacteria, Bacteroidetes, Proteobacteria and Actinobacteria. At a finer taxonomic resolution, black-backed jackals exhibited 69 bacterial taxa with proportions ≥0.1%, whereas cheetahs had only 42. Finally, oligotyping revealed that shared bacterial taxa consisted of distinct oligotype profiles. Thus, in contrast to 3% OTUs, oligotyping can detect fine-scale taxonomic differences between microbiomes.

  6. Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: a randomised cross-over trial.

    Science.gov (United States)

    Roager, Henrik Munch; Vogt, Josef K; Kristensen, Mette; Hansen, Lea Benedicte S; Ibrügger, Sabine; Mærkedahl, Rasmus B; Bahl, Martin Iain; Lind, Mads Vendelbo; Nielsen, Rikke L; Frøkiær, Hanne; Gøbel, Rikke Juul; Landberg, Rikard; Ross, Alastair B; Brix, Susanne; Holck, Jesper; Meyer, Anne S; Sparholt, Morten H; Christensen, Anders F; Carvalho, Vera; Hartmann, Bolette; Holst, Jens Juul; Rumessen, Jüri Johannes; Linneberg, Allan; Sicheritz-Pontén, Thomas; Dalgaard, Marlene D; Blennow, Andreas; Frandsen, Henrik Lauritz; Villas-Bôas, Silas; Kristiansen, Karsten; Vestergaard, Henrik; Hansen, Torben; Ekstrøm, Claus T; Ritz, Christian; Nielsen, Henrik Bjørn; Pedersen, Oluf Borbye; Gupta, Ramneek; Lauritzen, Lotte; Licht, Tine Rask

    2017-11-01

    To investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of ≥6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (pgut microbiome but reduced body weight and systemic low-grade inflammation. NCT01731366; Results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Sleep and the gut microbiome: antibiotic-induced depletion of the gut microbiota reduces nocturnal sleep in mice

    OpenAIRE

    Seebach, Bradley; Lendrum, Jonathan; Liu, Sumei; Klein, Barrett

    2017-01-01

    Several bacterial cell wall components such as peptidoglycan and muramyl peptide are potent inducers of mammalian slow-wave sleep when exogenously administered to freely behaving animals. It has been proposed that the native gut microflora may serve as a quasi-endogenous pool of somnogenic bacterial cell wall products given their quantity and close proximity to the intestinal portal. This proposal suggests that deliberate manipulation of the host's intestinal flora may elicit changes in host ...

  8. Alterations in Gut Microbiome Composition and Barrier Function Are Associated with Reproductive and Metabolic Defects in Women with Polycystic Ovary Syndrome (PCOS): A Pilot Study.

    Science.gov (United States)

    Lindheim, Lisa; Bashir, Mina; Münzker, Julia; Trummer, Christian; Zachhuber, Verena; Leber, Bettina; Horvath, Angela; Pieber, Thomas R; Gorkiewicz, Gregor; Stadlbauer, Vanessa; Obermayer-Pietsch, Barbara

    2017-01-01

    Polycystic ovary syndrome (PCOS) is a common female endocrinopathy of unclear origin characterized by hyperandrogenism, oligo-/anovulation, and ovarian cysts. Women with PCOS frequently display overweight, insulin resistance, and systemic low-grade inflammation. We hypothesized that endotoxemia resulting from a leaky gut is associated with inflammation, insulin resistance, fat accumulation, and hyperandrogenemia in PCOS. In this pilot study, we compared the stool microbiome, gut permeability, and inflammatory status of women with PCOS and healthy controls. 16S rRNA gene amplicon sequencing was performed on stool samples from 24 PCOS patients and 19 healthy controls. Data processing and microbiome analysis were conducted in mothur and QIIME using different relative abundance cut-offs. Gut barrier integrity, endotoxemia, and inflammatory status were evaluated using serum and stool markers and associations with reproductive, metabolic, and anthropometric parameters were investigated. The stool microbiome of PCOS patients showed a lower diversity and an altered phylogenetic composition compared to controls. We did not observe significant differences in any taxa with a relative abundance>1%. When looking at rare taxa, the relative abundance of bacteria from the phylum Tenericutes, the order ML615J-28 (phylum Tenericutes) and the family S24-7 (phylum Bacteroidetes) was significantly lower and associated with reproductive parameters in PCOS patients. Patients showed alterations in some, but not all markers of gut barrier function and endotoxemia. Patients with PCOS have a lower diversity and an altered phylogenetic profile in their stool microbiome, which is associated with clinical parameters. Gut barrier dysfunction and endotoxemia were not driving factors in this patient cohort, but may contribute to the clinical phenotype in certain PCOS patients.

  9. Alterations in Gut Microbiome Composition and Barrier Function Are Associated with Reproductive and Metabolic Defects in Women with Polycystic Ovary Syndrome (PCOS: A Pilot Study.

    Directory of Open Access Journals (Sweden)

    Lisa Lindheim

    Full Text Available Polycystic ovary syndrome (PCOS is a common female endocrinopathy of unclear origin characterized by hyperandrogenism, oligo-/anovulation, and ovarian cysts. Women with PCOS frequently display overweight, insulin resistance, and systemic low-grade inflammation. We hypothesized that endotoxemia resulting from a leaky gut is associated with inflammation, insulin resistance, fat accumulation, and hyperandrogenemia in PCOS. In this pilot study, we compared the stool microbiome, gut permeability, and inflammatory status of women with PCOS and healthy controls.16S rRNA gene amplicon sequencing was performed on stool samples from 24 PCOS patients and 19 healthy controls. Data processing and microbiome analysis were conducted in mothur and QIIME using different relative abundance cut-offs. Gut barrier integrity, endotoxemia, and inflammatory status were evaluated using serum and stool markers and associations with reproductive, metabolic, and anthropometric parameters were investigated.The stool microbiome of PCOS patients showed a lower diversity and an altered phylogenetic composition compared to controls. We did not observe significant differences in any taxa with a relative abundance>1%. When looking at rare taxa, the relative abundance of bacteria from the phylum Tenericutes, the order ML615J-28 (phylum Tenericutes and the family S24-7 (phylum Bacteroidetes was significantly lower and associated with reproductive parameters in PCOS patients. Patients showed alterations in some, but not all markers of gut barrier function and endotoxemia.Patients with PCOS have a lower diversity and an altered phylogenetic profile in their stool microbiome, which is associated with clinical parameters. Gut barrier dysfunction and endotoxemia were not driving factors in this patient cohort, but may contribute to the clinical phenotype in certain PCOS patients.

  10. A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS

    Science.gov (United States)

    2017-10-01

    distinguishable effects when transferred into susceptible animal models of the disease. 2. KEYWORDS Microbiome Multiple sclerosis Primary...had a significant impact on expenditures Nothing to report 5d. Significant changes in use or care of human subjects, vertebrate animals , biohazards...separating human reads from microbial that will be used in the shotgun metagenomics. Daniel McDonald Knight Bioinformatic s Programmer 1

  11. Gut Microbiome of Coexisting BaAka Pygmies and Bantu Reflects Gradients of Traditional Subsistence Patterns

    Czech Academy of Sciences Publication Activity Database

    Gomez, A.; Petrželková, Klára Judita; Burns, M. B.; Yeoman, C. J.; Amato, K. R.; Vlčková, K.; Modrý, David; Todd, A.; Robinson, C. A. J.; Remis, M. J.; Torralba, M.; Morton, E.; Umana, J. D.; Carbonero, F.; Gaskins, H. R.; Nelson, K. E.; Wilson, B. A.; Stumpf, R. M.; White, B. A.; Leigh, S. R.; Blekhman, R.

    2016-01-01

    Roč. 14, č. 9 (2016), s. 2142-2153 ISSN 2211-1247 Institutional support: RVO:60077344 Keywords : western lowland gorillas * microbiome * metabolomics * foraging ecology * anthropogenic interactions Subject RIV: EE - Microbiology, Virology Impact factor: 8.282, year: 2016

  12. Gut microbiome of coexisting BaAka pygmies and Bantu reflects gradients of traditional subsistence patterns

    Czech Academy of Sciences Publication Activity Database

    Gomez, A.; Petrželková, Klára Judita; Burns, M. B.; Yeoman, C. J.; Amato, K. R.; Vlčková, K.; Modrý, D.; Todd, A.; Robinson, C. A. J.; Remis, M. J.; Torralba, M.; Morton, E.; Umana, J. D.; Carbonero, F.; Gaskins, H. R.; Nelson, K.; Wilson, B. A.; Stumpf, R. M.; White, B. A.; Leigh, S. R.; Blekhman, R.

    2016-01-01

    Roč. 14, č. 9 (2016), s. 2142-2153 ISSN 2211-1247 R&D Projects: GA ČR GA206/09/0927 Institutional support: RVO:68081766 Keywords : western lowland gorillas * microbiome * metabolomics * foraging ecology * anthropogenic interactions Subject RIV: EG - Zoology Impact factor: 8.282, year: 2016

  13. The in-feed antibiotic carbadox induces phage gene transcription in the swine gut microbiome

    Science.gov (United States)

    Carbadox is a quinoxaline-di-N-oxide antibiotic fed to over 40 percent of young pigs in the U.S. and has been shown to induce phage DNA transduction in vitro; however, the effects of carbadox on swine microbiome functions are poorly understood. We investigated the in vivo effects of carbadox on swin...

  14. Impact of stress on the gut microbiome of free-ranging western lowland gorillas

    Czech Academy of Sciences Publication Activity Database

    Vlčková, Klára; Shutt-Phillips, K. A.; Heistermann, M.; Pafčo, B.; Petrželková, Klára Judita; Todd, A.; Modrý, D.; Nelson, K. E.; Wilson, B. A.; Stumpf, R. M.; White, B. A.; Leigh, S. R.; Gomez, A.

    2018-01-01

    Roč. 164, č. 1 (2018), s. 40-44 ISSN 1350-0872 Institutional support: RVO:68081766 Keywords : gastrointestinal-tract * disease * habituation * clostridium * disrupts * health * organ * flora * gastrointestinal microbiome * bacteria * stress * western lowland gorilla * faecal glucocorticoid metabolites Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 2.151, year: 2016

  15. Significant correlation between the infant gut microbiome and rotavirus vaccine response in rural Ghana

    NARCIS (Netherlands)

    Harris, V.C.; Armah, G.; Fuentes, S.; Korpela, K.E.; Parashar, U.; Victor, J.C.; Tate, J.; Weerth, C. de; Giaquinto, C.; Wiersinga, W.J.; Lewis, K.D.C.; Vos, W.M. de

    2017-01-01

    Background. Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and ninety-five percent of RV deaths occur in Africa and Asia where rotavirus vaccines (RVV) have lower efficacy. We hypothesize that differences in intestinal microbiome composition correlate with the

  16. Significant Correlation Between the Infant Gut Microbiome and Rotavirus Vaccine Response in Rural Ghana

    NARCIS (Netherlands)

    Harris, Vanessa C.; Armah, George; Fuentes Enriquez de Salamanca, Susana; Korpela, Katri E.; Parashar, Umesh; Victor, John C.; Tate, Jacqueline; Weerth, de Carolina; Giaquinto, Carlo; Wiersinga, Willem Joost; Lewis, Kristen D.C.; Vos, de Willem M.

    2017-01-01

    BACKGROUND:  Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and 95% of RV-associated deaths occur in Africa and Asia where RV vaccines (RVVs) have lower efficacy. We hypothesize that differences in intestinal microbiome composition correlate with the decreased

  17. Expression of arsenic resistance genes in the obligate anaerobe Bacteroides vulgatus ATCC 8482, a gut microbiome bacterium.

    Science.gov (United States)

    Li, Jiaojiao; Mandal, Goutam; Rosen, Barry P

    2016-06-01

    The response of the obligate anaerobe Bacteroides vulgatus ATCC 8482, a common human gut microbiota, to arsenic was determined. B. vulgatus ATCC 8482 is highly resistant to pentavalent As(V) and methylarsenate (MAs(V)). It is somewhat more sensitive to trivalent inorganic As(III) but 100-fold more sensitive to methylarsenite (MAs(III)) than to As(III). B. vulgatus ATCC 8482 has eight continuous genes in its genome that we demonstrate form an arsenical-inducible transcriptional unit. The first gene of this ars operon, arsR, encodes a putative ArsR As(III)-responsive transcriptional repressor. The next three genes encode proteins of unknown function. The remaining genes, arsDABC, have well-characterized roles in detoxification of inorganic arsenic, but there are no known genes for MAs(III) resistance. Expression of each gene after exposure to trivalent and pentavalent inorganic and methylarsenicals was analyzed. MAs(III) was the most effective inducer. The arsD gene was the most highly expressed of the ars operon genes. These results demonstrate that this anaerobic microbiome bacterium has arsenic-responsive genes that confer resistance to inorganic arsenic and may be responsible for the organism's ability to maintain its prevalence in the gut following dietary exposure to inorganic arsenic. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. A taxonomic signature of obesity in the microbiome? Getting to the guts of the matter

    OpenAIRE

    Pollard, Katherine; Finucane, MM; Sharpton, TJ; Laurent, TJ; Pollard, KS

    2014-01-01

    Obesity is an important and intractable public health problem. In addition to the well-known risk factors of behavior, diet, and genetics, gut microbial communities were recently identified as another possible source of risk and a potential therapeutic tar

  19. Feeding the microbiota-gut-brain axis: diet, microbiome, and neuropsychiatry.

    Science.gov (United States)

    Sandhu, Kiran V; Sherwin, Eoin; Schellekens, Harriët; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

    2017-01-01

    The microbial population residing within the human gut represents one of the most densely populated microbial niche in the human body with growing evidence showing it playing a key role in the regulation of behavior and brain function. The bidirectional communication between the gut microbiota and the brain, the microbiota-gut-brain axis, occurs through various pathways including the vagus nerve, the immune system, neuroendocrine pathways, and bacteria-derived metabolites. This axis has been shown to influence neurotransmission and the behavior that are often associated with neuropsychiatric conditions. Therefore, research targeting the modulation of this gut microbiota as a novel therapy for the treatment of various neuropsychiatric conditions is gaining interest. Numerous factors have been highlighted to influence gut microbiota composition, including genetics, health status, mode of birth, and environment. However, it is diet composition and nutritional status that has repeatedly been shown to be one of the most critical modifiable factors regulating the gut microbiota at different time points across the lifespan and under various health conditions. Thus the microbiota is poised to play a key role in nutritional interventions for maintaining brain health. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Quantitatively different, yet qualitatively alike: a meta-analysis of the mouse core gut microbiome with a view towards the human gut microbiome.

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    Lukasz Krych

    Full Text Available BACKGROUND: A number of human diseases such as obesity and diabetes are associated with changes or imbalances in the gut microbiota (GM. Laboratory mice are commonly used as experimental models for such disorders. The introduction and dynamic development of next generation sequencing techniques have enabled detailed mapping of the GM of both humans and animal models. Nevertheless there is still a significant knowledge gap regarding the human and mouse common GM core and thus the applicability of the latter as an animal model. The aim of the present study was to identify inter- and intra-individual differences and similarities between the GM composition of particular mouse strains and humans. METHODOLOGY/PRINCIPAL FINDINGS: A total of 1509428 high quality tag-encoded partial 16S rRNA gene sequences determined using 454/FLX Titanium (Roche pyro-sequencing reflecting the GM composition of 32 human samples from 16 individuals and 88 mouse samples from three laboratory mouse strains commonly used in diabetes research were analyzed using Principal Coordinate Analysis (PCoA, nonparametric multivariate analysis of similarity (ANOSIM and alpha diversity measures. A reliable cutoff threshold for low abundant taxa estimated on the basis of the present study is recommended for similar trials. CONCLUSIONS/SIGNIFICANCE: Distinctive quantitative differences in the relative abundance of most taxonomic groups between the examined categories were found. All investigated mouse strains clustered separately, but with a range of shared features when compared to the human GM. However, both mouse fecal, caecal and human fecal samples shared to a large extent not only representatives of the same phyla, but also a substantial fraction of common genera, where the number of shared genera increased with sequencing depth. In conclusion, the GM of mice and humans is quantitatively different (in terms of abundance of specific phyla and species but share a large qualitatively

  1. Dietary Alteration of the Gut Microbiome and Its Impact on Weight and Fat Mass: A Systematic Review and Meta-Analysis

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    George Kunnackal John

    2018-03-01

    Full Text Available Dietary alteration of the gut microbiome is an important target in the treatment of obesity. Animal and human studies have shown bidirectional weight modulation based on the probiotic formulation used. In this study, we systematically reviewed the literature and performed a meta-analysis to assess the impact of prebiotics, probiotics and synbiotics on body weight, body mass index (BMI and fat mass in adult human subjects. We searched Medline (PubMed, Embase, the Cochrane Library and the Web of Science to identify 4721 articles, of which 41 were subjected to full-text screening, yielding 21 included studies with 33 study arms. Probiotic use was associated with significant decreases in BMI, weight and fat mass. Studies of subjects consuming prebiotics demonstrated a significant reduction in body weight, whereas synbiotics did not show an effect. Overall, when the utilization of gut microbiome-modulating dietary agents (prebiotic/probiotic/synbiotic was compared to placebo, there were significant decreases in BMI, weight and fat mass. In summary, dietary agents for the modulation of the gut microbiome are essential tools in the treatment of obesity and can lead to significant decreases in BMI, weight and fat mass. Further studies are needed to identify the ideal dose and duration of supplementation and to assess the durability of this effect.

  2. Th17 Cells in Type 1 Diabetes: Role in the Pathogenesis and Regulation by Gut Microbiome

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    Yangyang Li

    2015-01-01

    Full Text Available Type 1 diabetes (T1D is an autoimmune disease which is characterized by progressive destruction of insulin producing pancreatic islet β cells. The risk of developing T1D is determined by both genetic and environmental factors. A growing body of evidence supports an important role of T helper type 17 (Th17 cells along with impaired T regulatory (Treg cells in the development of T1D in animal models and humans. Alteration of gut microbiota has been implicated to be responsible for the imbalance between Th17 and Treg cells. However, there is controversy concerning a pathogenic versus protective role of Th17 cells in murine models of diabetes in the context of influence of gut microbiota. In this review we will summarize current knowledge about Th17 cells and gut microbiota involved in T1D and propose Th17 targeted therapy in children with islet autoimmunity to prevent progression to overt diabetes.

  3. Connecting the immune system, systemic chronic inflammation and the gut microbiome: The role of sex.

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    Rizzetto, Lisa; Fava, Francesca; Tuohy, Kieran M; Selmi, Carlo

    2018-05-31

    Unresolved low grade systemic inflammation represents the underlying pathological mechanism driving immune and metabolic pathways involved in autoimmune diseases (AID). Mechanistic studies in animal models of AID and observational studies in patients have found alterations in gut microbiota communities and their metabolites, suggesting a microbial contribution to the onset or progression of AID. The gut microbiota and its metabolites have been shown to influence immune functions and immune homeostasis both within the gut and systematically. Microbial derived-short chain fatty acid (SCFA) and bio-transformed bile acid (BA) have been shown to influence the immune system acting as ligands specific cell signaling receptors like GPRCs, TGR5 and FXR, or via epigenetic processes. Similarly, intestinal permeability (leaky gut) and bacterial translocation are important contributors to chronic systemic inflammation and, without repair of the intestinal barrier, might represent a continuous inflammatory stimulus capable of triggering autoimmune processes. Recent studies indicate gender-specific differences in immunity, with the gut microbiota shaping and being concomitantly shaped by the hormonal milieu governing differences between the sexes. A bi-directional cross-talk between microbiota and the endocrine system is emerging with bacteria being able to produce hormones (e.g. serotonin, dopamine and somatostatine), respond to host hormones (e.g. estrogens) and regulate host hormones' homeostasis (e.g by inhibiting gene prolactin transcription or converting glucocorticoids to androgens). We review herein how gut microbiota and its metabolites regulate immune function, intestinal permeability and possibly AID pathological processes. Further, we describe the dysbiosis within the gut microbiota observed in different AID and speculate how restoring gut microbiota composition and its regulatory metabolites by dietary intervention including prebiotics and probiotics could help in

  4. Differential effects of whisky brands on human gut microbiome and fecal metabolome

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    Priyanka Sarkar

    2017-10-01

    Full Text Available The gut bacteria have significant impact on human physiology and are influenced by dietary habit [1]. Apart from normal diet, alcoholic beverages have also been shown to influence gut microbial makeup. The wine polyphenols have been linked to increase the beneficial bacteria in the gut after 4 weeks of consumption [2]. Consumption of alcoholic beverages for longer period (>10 years has also been correlated to detrimental gut bacterial dysbiosis [3]. The contrasting effects of alcoholic beverages in these two studies necessitate further research. Globally, 45.7% of alcoholic drinkers are spirit drinkers with India having the highest (71% [4]. In India whisky is preferred by most of the drinkers and 1400 million liters of whisky was consumed in India in the year 2012 [5]. Till date, no study has been reported to understand the effect of long-term consumption of different types of whisky on gut bacterial profile (GBP. In this purview apilot study of gut bacterial and metabolite profile was performed between the whisky drinker (n=18 and non-drinker (n=8 along with rice beer drinkers (n=3. PCR-denaturing gradient gel electrophoresis (PCR-DGGE coupled with next generation sequencing (NGS analysis on illumina miseq platform revealed decrease in gut bacterial diversity in the drinkers compared to the non-drinkers. The whisky types have differential effects on the GBP. The GBP of whisky type 1 drinkers had higher abundance of Clostridiaceae and Enterobacteriaceae (fold change log 2: 3.33 & 3.1537, respectively; p< 0.002 in comparison to the non-drinker group, while the type 2 whisky drinkers had increased abundance of Lactococcus and Streptococcus (fold change log 2: 9.1827 & 4.2986; p< 0.002 compared to the non-drinker group. The butyric acid producing genera, Ruminococcaceae was found to be decreased in both the whisky drinking cohorts (fold change log 2: -1.5449 & -2.7327, respectively; p<0.002. Short-chain fatty acids (SCFA, mainly butyric acid

  5. Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial.

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    Judit Villar-García

    Full Text Available Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly reduced plasma levels of bacterial translocation (Lipopolysaccharide-binding protein or LBP and systemic inflammation (IL-6 in 44 HIV virologically suppressed patients, half of whom (n = 22 had immunologic non-response to antiretroviral therapy (<270 CD4+Tcells/μL despite long-term suppressed viral load. The aim of the present study was to investigate if this beneficial effect of the probiotic Saccharomyces boulardii is due to modified gut microbiome composition, with a decrease of some species associated with higher systemic levels of microbial translocation and inflammation. In this study, we used 16S rDNA gene amplification and parallel sequencing to analyze the probiotic impact on the composition of the gut microbiome (faecal samples in these 44 patients randomized to receive oral supplementation with probiotic or placebo for 12 weeks. Compared to the placebo group, in individuals treated with probiotic we observed lower concentrations of some gut species, such as those of the Clostridiaceae family, which were correlated with systemic levels of bacterial translocation and inflammation markers. In a sub-study of these patients, we observed significantly higher parameters of microbial translocation (LBP, soluble CD14 and systemic inflammation in immunologic non-responders than in immunologic responders, which was correlated with a relative abundance of specific gut bacterial groups (Lachnospiraceae genus and Proteobacteria. Thus, in this work, we propose

  6. The human gut microbiome as source of innovation for health: Which physiological and therapeutic outcomes could we expect?

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    Doré, Joël; Multon, Marie-Christine; Béhier, Jehan-Michel

    2017-02-01

    From the moment of birth, each human being builds a microbe-host symbiosis which is key for the preservation of its health and well-being. This personal symbiotic coexistence is the result of progressive enrichments in microorganism diversity through external supplies. This diversity is nowadays massively overthrown by drastic changes related to clinical practice in birth management, environmental exposure, nutrition and healthcare behaviors. The last two generations have been the frame of massive modifications in life and food habits, with people being more and more sedentary, overfed and permeated with drugs and pollutants. We are now able to measure the impact of these changes on the gut microbiota diversity. Concomitantly, these modifications of lifestyle were associated with a dramatic increase in incidence of immune-mediated diseases including metabolic, allergic and inflammatory diseases and most likely neurodegenerative and psychiatric disorders. Microbiota is becoming a hot topic in the scientific community and in the mainstream media. The number of scientific publications increased by up to a factor three over the last five years, with gastrointestinal and metabolic diseases being the most productive areas. In the intellectual property landscape, the patent families on microbiota have more than doubled in the meantime. In parallel, funding either from National Institutes (e.g. from NIH which funds research mainly in the field of allergies, infections, cancer and cardiovascular diseases, from the White House which launched the national microbiome initiative) or by pharmaceutical companies follow the same trend, showing a boost and a strong support in the research field on microbiota. All major health players are investing in microbiome research as shown by the number of deals signed and by funding during 2015. The Giens round table addressed how the medicine of tomorrow, considering human beings as a human-microbe symbiotic supraorganism, could leverage

  7. Preservation of three-dimensional spatial structure in the gut microbiome.

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    Yuko Hasegawa

    Full Text Available Preservation of three-dimensional structure in the gut is necessary in order to analyze the spatial organization of the gut microbiota and gut luminal contents. In this study, we evaluated preparation methods for mouse gut with the goal of preserving micron-scale spatial structure while performing fluorescence imaging assays. Our evaluation of embedding methods showed that commonly used media such as Tissue-Tek Optimal Cutting Temperature (OCT compound, paraffin, and polyester waxes resulted in redistribution of luminal contents. By contrast, a hydrophilic methacrylate resin, Technovit H8100, preserved three-dimensional organization. Our mouse intestinal preparation protocol optimized using the Technovit H8100 embedding method was compatible with microbial fluorescence in situ hybridization (FISH and other labeling techniques, including immunostaining and staining with both wheat germ agglutinin (WGA and 4', 6-diamidino-2-phenylindole (DAPI. Mucus could be visualized whether the sample was fixed with paraformaldehyde (PFA or with Carnoy's fixative. The protocol optimized in this study enabled simultaneous visualization of micron-scale spatial patterns formed by microbial cells in the mouse intestines along with biogeographical landmarks such as host-derived mucus and food particles.

  8. Impact of short-chain galactooligosaccharides on the gut microbiome of lactose-intolerant individuals.

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    Azcarate-Peril, M Andrea; Ritter, Andrew J; Savaiano, Dennis; Monteagudo-Mera, Andrea; Anderson, Carlton; Magness, Scott T; Klaenhammer, Todd R

    2017-01-17

    Directed modulation of the colonic bacteria to metabolize lactose effectively is a potentially useful approach to improve lactose digestion and tolerance. A randomized, double-blind, multisite placebo-controlled trial conducted in human subjects demonstrated that administration of a highly purified (>95%) short-chain galactooligosaccharide (GOS), designated "RP-G28," significantly improved clinical outcomes for lactose digestion and tolerance. In these individuals, stool samples were collected pretreatment (day 0), after GOS treatment (day 36), and 30 d after GOS feeding stopped and consumption of dairy products was encouraged (day 66). In this study, changes in the fecal microbiome were investigated using 16S rRNA amplicon pyrosequencing and high-throughput quantitative PCR. At day 36, bifidobacterial populations were increased in 27 of 30 of GOS subjects (90%), demonstrating a bifidogenic response in vivo. Relative abundance of lactose-fermenting Bifidobacterium, Faecalibacterium, and Lactobacillus were significantly increased in response to GOS. When dairy was introduced into the diet, lactose-fermenting Roseburia species increased from day 36 to day 66. The results indicated a definitive change in the fecal microbiome of lactose-intolerant individuals, increasing the abundance of lactose-metabolizing bacteria that were responsive to dietary adaptation to GOS. This change correlated with clinical outcomes of improved lactose tolerance.

  9. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug

    DEFF Research Database (Denmark)

    Wu, Hao; Esteve, Eduardo; Tremaroli, Valentina

    2017-01-01

    months and showed that metformin had strong effects on the gut microbiome. These results were verified in a subset of the placebo group that switched to metformin 6 months after the start of the trial. Transfer of fecal samples (obtained before and 4 months after treatment) from metformin-treated donors......Metformin is widely used in the treatment of type 2 diabetes (T2D), but its mechanism of action is poorly defined. Recent evidence implicates the gut microbiota as a site of metformin action. In a double-blind study, we randomized individuals with treatment-naive T2D to placebo or metformin for 4...... to germ-free mice showed that glucose tolerance was improved in mice that received metformin-altered microbiota. By directly investigating metformin-microbiota interactions in a gut simulator, we showed that metformin affected pathways with common biological functions in species from two different phyla...

  10. A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS

    Science.gov (United States)

    2016-10-01

    inflammatory and regulatory immune cell populations thus leading to disease in genetically susceptible hosts. Furthermore, we hypothesize that gut...techniques Nothing to report 6d. Inventions, patent applications , and/or licenses Nothing to report 6e. Other Products (Reportable outcomes...Evguenia Kopylova Knight Post Doc 4 Development of fast algorithms for OTU picking 8 that will be used in the 16S analysis and fast matching

  11. Cross sectional evaluation of the gut-microbiome metabolome axis in an Italian cohort of IBD patients.

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    Santoru, Maria Laura; Piras, Cristina; Murgia, Antonio; Palmas, Vanessa; Camboni, Tania; Liggi, Sonia; Ibba, Ivan; Lai, Maria Antonia; Orrù, Sandro; Blois, Sylvain; Loizedda, Anna Lisa; Griffin, Julian Leether; Usai, Paolo; Caboni, Pierluigi; Atzori, Luigi; Manzin, Aldo

    2017-08-25

    Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract of uncertain origin, which includes ulcerative colitis (UC) and Crohn's disease (CD). The composition of gut microbiota may change in IBD affected individuals, but whether dysbiosis is the cause or the consequence of inflammatory processes in the intestinal tissue is still unclear. Here, the composition of the microbiota and the metabolites in stool of 183 subjects (82 UC, 50 CD, and 51 healthy controls) were determined. The metabolites content and the microbiological profiles were significantly different between IBD and healthy subjects. In the IBD group, Firmicutes, Proteobacteria, Verrucomicrobia, and Fusobacteria were significantly increased, whereas Bacteroidetes and Cyanobacteria were decreased. At genus level Escherichia, Faecalibacterium, Streptococcus, Sutterella and Veillonella were increased, whereas Bacteroides, Flavobacterium, and Oscillospira decreased. Various metabolites including biogenic amines, amino acids, lipids, were significantly increased in IBD, while others, such as two B group vitamins, were decreased in IBD compared to healthy subjects. This study underlines the potential role of an inter-omics approach in understanding the metabolic pathways involved in IBD. The combined evaluation of metabolites and fecal microbiome can be useful to discriminate between healthy subjects and patients with IBD.

  12. The Gut-Brain Axis and the Microbiome: Clues to Pathophysiology and Opportunities for Novel Management Strategies in Irritable Bowel Syndrome (IBS

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    Eamonn M.M. Quigley

    2018-01-01

    Full Text Available Irritable bowel syndrome (IBS is one of the most common of all medical disorders worldwide and, while for some it represents no more than a nuisance, for others it imposes significant negative impacts on daily life and activities. IBS is a heterogeneous disorder and may well have a number of causes which may lie anywhere from the external environment to the contents of the gut lumen and from the enteric neuromuscular apparatus and the gut immune system to the central nervous system. Consequently, the paradigm of the gut-brain axis, which includes the participation of these various factors, has proven a useful model to assist clinicians and patients alike in understanding the genesis of symptoms in IBS. Now, given the widespread interest in the gut microbiome in health and disease, in general, reports of disordered enteric bacterial communities in IBS, and experimental data to indicate that components of the gut microbiota can influence brain morphology and function, as well as behavior and cognition, this concept has been extended to encompass the microbiota-gut-brain axis. The implications of this novel concept to the assessment and management of IBS will be explored in this review.

  13. Dietary pomegranate extract and inulin affect gut microbiome differentially in mice fed an obesogenic diet.

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    Zhang, Song; Yang, Jieping; Henning, Susanne M; Lee, Rupo; Hsu, Mark; Grojean, Emma; Pisegna, Rita; Ly, Austin; Heber, David; Li, Zhaoping

    2017-12-01

    Growing evidence suggests that dysbiosis of gut microbiota is associated with pathogenesis of a variety of human diseases. Using dietary intervention to shape the composition and metabolism of the gut microbiota is increasingly recognized. In the present study, we investigated the effects of polysaccharide inulin and polyphenol-rich pomegranate extract (PomX) alone or in combination on the cecal microbiota composition and function in a diet induced obesity mouse model. Male C57BL/6 mice were randomly divided into four experimental groups and consumed either high-fat/high-sucrose [HF/HS (32% energy from fat, 25% energy from sucrose, 17% energy from protein)] diet, HF/HS diet supplemented with PomX (0.25%), or inulin (9%) or PomX and inulin in combination for 4 weeks. In mice fed the PomX-diet the proportion of Turicibacteraceae and Ruminococcaceae was significantly increased compared to the control HF/HS diet. Supplementation with inulin alone and inulin + PomX combination significantly increased the proportion of Verrucomicrobiaceae (A. muciniphila) and decreased Clostridiaceae. Only mice fed the inulin diet experienced an increase in serum lipopolysaccharide (LPS) and monocyte chemoattractant protein 1 (MCP-1), which was reversed when feeding the inulin + PomX diet. Feeding the inulin + PomX diet was associated with a significant increase in Bifidobacteriaceae and Rikenellaceae, which may have contributed to the reduction of endotoxemia markers. Inulin supplementation showed lower species richness of gut microbiota compared to mice fed with HF/HS or HF/HS/PomX, and the reduction was reversed by the addition of PomX. Inulin alone and in combination with PomX had distinct microbial clusters determined by both weighted and unweighted UniFrac Beta-Diversity principle coordinate analysis. A total of 19 KEGG biological pathways were significantly regulated in the gut microbiota with PomX and inulin alone or combined treatment. Inulin significantly enhanced KEGG

  14. Distinct signatures of host–microbial meta-metabolome and gut microbiome in two C57BL/6 strains under high-fat diet

    Science.gov (United States)

    Walker, Alesia; Pfitzner, Barbara; Neschen, Susanne; Kahle, Melanie; Harir, Mourad; Lucio, Marianna; Moritz, Franco; Tziotis, Dimitrios; Witting, Michael; Rothballer, Michael; Engel, Marion; Schmid, Michael; Endesfelder, David; Klingenspor, Martin; Rattei, Thomas; Castell, Wolfgang zu; de Angelis, Martin Hrabé; Hartmann, Anton; Schmitt-Kopplin, Philippe

    2014-01-01

    A combinatory approach using metabolomics and gut microbiome analysis techniques was performed to unravel the nature and specificity of metabolic profiles related to gut ecology in obesity. This study focused on gut and liver metabolomics of two different mouse strains, the C57BL/6J (C57J) and the C57BL/6N (C57N) fed with high-fat diet (HFD) for 3 weeks, causing diet-induced obesity in C57N, but not in C57J mice. Furthermore, a 16S-ribosomal RNA comparative sequence analysis using 454 pyrosequencing detected significant differences between the microbiome of the two strains on phylum level for Firmicutes, Deferribacteres and Proteobacteria that propose an essential role of the microbiome in obesity susceptibility. Gut microbial and liver metabolomics were followed by a combinatory approach using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) and ultra performance liquid chromatography time of tlight MS/MS with subsequent multivariate statistical analysis, revealing distinctive host and microbial metabolome patterns between the C57J and the C57N strain. Many taurine-conjugated bile acids (TBAs) were significantly elevated in the cecum and decreased in liver samples from the C57J phenotype likely displaying different energy utilization behavior by the bacterial community and the host. Furthermore, several metabolite groups could specifically be associated with the C57N phenotype involving fatty acids, eicosanoids and urobilinoids. The mass differences based metabolite network approach enabled to extend the range of known metabolites to important bile acids (BAs) and novel taurine conjugates specific for both strains. In summary, our study showed clear alterations of the metabolome in the gastrointestinal tract and liver within a HFD-induced obesity mouse model in relation to the host–microbial nutritional adaptation. PMID:24906017

  15. Gut microbiome diversity influenced more by the Westernized dietary regime than the body mass index as assessed using effect size statistic.

    Science.gov (United States)

    Davis, Shannon C; Yadav, Jagjit S; Barrow, Stephanie D; Robertson, Boakai K

    2017-08-01

    Human gut microbiome dysbiosis has been associated with the onset of metabolic diseases and disorders. However, the critical factors leading to dysbiosis are poorly understood. In this study, we provide increasing evidence of the association of diet type and body mass index (BMI) and how they relatively influence the taxonomic structure of the gut microbiota with respect to the causation of gut microbiome dysbiosis. The study included randomly selected Alabama residents (n = 81), including females (n = 45) and males (n = 36). The demographics data included age (33 ± 13.3 years), height (1.7 ± 0.11 meters), and weight (82.3 ± 20.6 kg). The mean BMI was 28.3 ± 7.01, equating to an overweight BMI category. A cross-sectional case-control design encompassing the newly recognized effect size approach to bioinformatics analysis was used to analyze data from donated stool samples and accompanying nutrition surveys. We investigated the microbiome variations in the Bacteroidetes-Firmicutes ratio relative to BMI, food categories, and dietary groups at stratified abundance percentages of gut microbiota diversity than an increased BMI with an effect size of 0.16. This implied Westernized diet as a critical factor in causing dysbiosis as compared to an overweight or obese body mass index. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  16. Role of the Gut Microbiome in Obstructive Sleep Apnea-Induced Hypertension.

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    Durgan, David J; Ganesh, Bhanu P; Cope, Julia L; Ajami, Nadim J; Phillips, Sharon C; Petrosino, Joseph F; Hollister, Emily B; Bryan, Robert M

    2016-02-01

    Individuals suffering from obstructive sleep apnea (OSA) are at increased risk for systemic hypertension. The importance of a healthy gut microbiota, and detriment of a dysbiotic microbiota, on host physiology is becoming increasingly evident. We tested the hypothesis that gut dysbiosis contributes to hypertension observed with OSA. OSA was modeled in rats by inflating a tracheal balloon during the sleep cycle (10-s inflations, 60 per hour). On normal chow diet, OSA had no effect on blood pressure; however, in rats fed a high-fat diet, blood pressure increased 24 and 29 mm Hg after 7 and 14 days of OSA, respectively (Phypertensive OSA rats on high-fat diet into OSA recipient rats on normal chow diet (shown to be normotensive) resulted in hypertension similar to that of the donor (increased 14 and 32 mm Hg after 7 and 14 days of OSA, respectively; Phypertension, and suggest that manipulation of the microbiota may be a viable treatment for OSA-induced, and possibly other forms of, hypertension. © 2015 American Heart Association, Inc.

  17. Importance of the fat content within the cheese-matrix for blood lipid profile, faecal fat excretion, and gut microbiome in growing pigs

    DEFF Research Database (Denmark)

    Thorning, Tanja K.; Raben, Anne; Bendsen, Nathalie T.

    2016-01-01

    and energy excretion and gut microbiome in pigs. A 14-d run-in period was followed by 14-d interventions with macronutrient-matched diets. Fasting total cholesterol and HDL-cholesterol after 14 days were higher in REG compared with BUT, but only tended to be higher in RED. Compared with BUT, REG and RED had......Cheese and butter have been shown to affect blood lipids differently. This parallel-arm, randomised, controlled study in 36 crossbred growing sows compared the effect of diets with either regular-fat cheese (REG), reduced-fat cheese + butter (RED) or butter (BUT) on blood lipids, faecal fat...... higher faecal fat excretion. Faecal energy excretion was only higher in REG, and this correlated with a lower microbiome Firmicutes-to-Bacteroidetes ratio. In conclusion, dairy fat consumed as cheese or butter caused different metabolic effects. Differences between reduced-fat cheese+butter and butter...

  18. Review of the gut microbiome and esophageal cancer: Pathogenesis and potential clinical implications.

    Science.gov (United States)

    Baba, Yoshifumi; Iwatsuki, Masaaki; Yoshida, Naoya; Watanabe, Masayuki; Baba, Hideo

    2017-06-01

    Esophageal cancer ranks among the most aggressive malignant diseases. The limited improvements in treatment outcomes provided by conventional therapies have prompted us to seek innovative strategies for treating this cancer. More than 100 trillion microorganisms inhabit the human intestinal tract and play a crucial role in health and disease conditions, including cancer. The human intestinal microbiome is thought to influence tumor development and progression in the gastrointestinal tract by various mechanisms. For example, Fusobacterium nucleatum , which primarily inhabits the oral cavity and causes periodontal disease, might contribute to aggressive tumor behavior through activation of chemokines such as CCL20 in esophageal cancer tissue. Composition of the intestinal microbiota is influenced by diet, lifestyle, antibiotics, and pro- and prebiotics. Therefore, by better understanding how the bacterial microbiota contributes to esophageal carcinogenesis, we might develop novel cancer prevention and treatment strategies through targeting the gastrointestinal microflora. This review discusses the current knowledge, available data and information on the relationship of microbiota with esophagitis, Barrett's esophagus, esophageal adenocarcinoma and squamous cell carcinoma.

  19. Composition, Diversity and Abundance of Gut Microbiome in Prediabetes and Type 2 Diabetes.

    Science.gov (United States)

    Lambeth, Stacey M; Carson, Trechelle; Lowe, Janae; Ramaraj, Thiruvarangan; Leff, Jonathan W; Luo, Li; Bell, Callum J; Shah, Vallabh O

    2015-12-26

    Association between type 2 diabetes (T2DM) and compositional changes in the gut micro biota is established, however little is known about the dysbiosis in early stages of Prediabetes (preDM). The purpose of this investigation is to elucidate the characteristics of the gut micro biome in preDM and T2DM, compared to Non-Diabetic (nonDM) subjects. Forty nine subjects were recruited for this study, 15 nonDM, 20 preDM and 14 T2DM. Bacterial community composition and diversity were investigated in fecal DNA samples using Illumina sequencing of the V4 region within the 16S rRNA gene. The five most abundant phyla identified were: Bacteroidetes, Firmicutes, Proteobacteria, Verrucomicrobia , and Actinobacteria . Class Chloracido bacteria was increased in preDM compared to T2DM (p = 0.04). An unknown genus from family Pseudonocardiaceae was significantly present in preDM group compared to the others (p = 0.04). Genus Collinsella , and an unknown genus belonging to family Enterobacteriaceae were both found to be significantly increased in T2DM compared to the other groups (Collinsella, and p = 0.03, Enterobacteriaceae genus p = 0.02). PERMANOVA and Mantel tests performed did not reveal a relationship between overall composition and diagnosis group or HbA1C level. This study identified dysbiosis associated with both preDM and T2DM, specifically at the class and genus levels suggesting that earlier treatment in preDM could possibly have an impact on the intestinal micro flora transitioning to T2DM.

  20. Gut Microbiome Associates With Lifetime Cardiovascular Disease Risk Profile Among Bogalusa Heart Study Participants.

    Science.gov (United States)

    Kelly, Tanika N; Bazzano, Lydia A; Ajami, Nadim J; He, Hua; Zhao, Jinying; Petrosino, Joseph F; Correa, Adolfo; He, Jiang

    2016-09-30

    Few studies have systematically assessed the influence of gut microbiota on cardiovascular disease (CVD) risk. To examine the association between gut microbiota and lifetime CVD risk profile among 55 Bogalusa Heart Study participants with the highest and 57 with the lowest lifetime burdens of CVD risk factors. 16S ribosomal RNA sequencing was conducted on microbial DNA extracted from stool samples of the Bogalusa Heart Study participants. α Diversity, including measures of richness and evenness, and individual genera were tested for associations with lifetime CVD risk profile. Multivariable regression techniques were used to adjust for age, sex, and race (model 1), along with body mass index (model 2) and both body mass index and diet (model 3). In model 1, odds ratios (95% confidence intervals) for each SD increase in richness, measured by the number of observed operational taxonomic units, Chao 1 index, and abundance-based coverage estimator, were 0.62 (0.39-0.99), 0.61 (0.38-0.98), and 0.63 (0.39-0.99), respectively. Associations were consistent in models 2 and 3. Four genera were enriched among those with high versus low CVD risk profile in all models. Model 1 P values were 2.12×10(-3), 7.95×10(-5), 4.39×10(-4), and 1.51×10(-4) for Prevotella 2, Prevotella 7, Tyzzerella, and Tyzzerella 4, respectively. Two genera were depleted among those with high versus low CVD risk profile in all models. Model 1 P values were 2.96×10(-6) and 1.82×10(-4) for Alloprevotella and Catenibacterium, respectively. The current study identified associations of overall microbial richness and 6 microbial genera with lifetime CVD risk. © 2016 American Heart Association, Inc.

  1. Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model.

    Science.gov (United States)

    Yu, Yueyue; Lu, Lei; Sun, Jun; Petrof, Elaine O; Claud, Erika C

    2016-09-01

    Development of the infant small intestine is influenced by bacterial colonization. To promote establishment of optimal microbial communities in preterm infants, knowledge of the beneficial functions of the early gut microbiota on intestinal development is needed. The purpose of this study was to investigate the impact of early preterm infant microbiota on host gut development using a gnotobiotic mouse model. Histological assessment of intestinal development was performed. The differentiation of four epithelial cell lineages (enterocytes, goblet cells, Paneth cells, enteroendocrine cells) and tight junction (TJ) formation was examined. Using weight gain as a surrogate marker for health, we found that early microbiota from a preterm infant with normal weight gain (MPI-H) induced increased villus height and crypt depth, increased cell proliferation, increased numbers of goblet cells and Paneth cells, and enhanced TJs compared with the changes induced by early microbiota from a poor weight gain preterm infant (MPI-L). Laser capture microdissection (LCM) plus qRT-PCR further revealed, in MPI-H mice, a higher expression of stem cell marker Lgr5 and Paneth cell markers Lyz1 and Cryptdin5 in crypt populations, along with higher expression of the goblet cell and mature enterocyte marker Muc3 in villus populations. In contrast, MPI-L microbiota failed to induce the aforementioned changes and presented intestinal characteristics comparable to a germ-free host. Our data demonstrate that microbial communities have differential effects on intestinal development. Future studies to identify pioneer settlers in neonatal microbial communities necessary to induce maturation may provide new insights for preterm infant microbial ecosystem therapeutics. Copyright © 2016 the American Physiological Society.

  2. Gut

    DEFF Research Database (Denmark)

    Muscogiuri, Giovanna; Balercia, Giancarlo; Barrea, Luigi

    2017-01-01

    The gut regulates glucose and energy homeostasis; thus, the presence of ingested nutrients into the gut activates sensing mechanisms that affect both glucose homeostasis and regulate food intake. Increasing evidence suggest that gut may also play a key role in the pathogenesis of type 2 diabetes...... which may be related to both the intestinal microbiological profile and patterns of gut hormones secretion. Intestinal microbiota includes trillions of microorganisms but its composition and function may be adversely affected in type 2 diabetes. The intestinal microbiota may be responsible...... metabolism. Thus, the aim of this manuscript is to review the current evidence on the role of the gut in the pathogenesis of type 2 diabetes, taking into account both hormonal and microbiological aspects....

  3. Development of SYN-004, an oral beta-lactamase treatment to protect the gut microbiome from antibiotic-mediated damage and prevent Clostridium difficile infection.

    Science.gov (United States)

    Kaleko, Michael; Bristol, J Andrew; Hubert, Steven; Parsley, Todd; Widmer, Giovanni; Tzipori, Saul; Subramanian, Poorani; Hasan, Nur; Koski, Perrti; Kokai-Kun, John; Sliman, Joseph; Jones, Annie; Connelly, Sheila

    2016-10-01

    The gut microbiome, composed of the microflora that inhabit the gastrointestinal tract and their genomes, make up a complex ecosystem that can be disrupted by antibiotic use. The ensuing dysbiosis is conducive to the emergence of opportunistic pathogens such as Clostridium difficile. A novel approach to protect the microbiome from antibiotic-mediated dysbiosis is the use of beta-lactamase enzymes to degrade residual antibiotics in the gastrointestinal tract before the microflora are harmed. Here we present the preclinical development and early clinical studies of the beta-lactamase enzymes, P3A, currently referred to as SYN-004, and its precursor, P1A. Both P1A and SYN-004 were designed as orally-delivered, non-systemically available therapeutics for use with intravenous beta-lactam antibiotics. SYN-004 was engineered from P1A, a beta-lactamase isolated from Bacillus licheniformis, to broaden its antibiotic degradation profile. SYN-004 efficiently hydrolyses penicillins and cephalosporins, the most widely used IV beta-lactam antibiotics. In animal studies, SYN-004 degraded ceftriaxone in the GI tract of dogs and protected the microbiome of pigs from ceftriaxone-induced changes. Phase I clinical studies demonstrated SYN-004 safety and tolerability. Phase 2 studies are in progress to assess the utility of SYN-004 for the prevention of antibiotic-associated diarrhea and Clostridium difficile disease. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. The effect of the timing of exposure to Campylobacter jejuni on the gut microbiome and inflammatory responses of broiler chickens.

    Science.gov (United States)

    Connerton, Phillippa L; Richards, Philip J; Lafontaine, Geraldine M; O'Kane, Peter M; Ghaffar, Nacheervan; Cummings, Nicola J; Smith, Darren L; Fish, Neville M; Connerton, Ian F

    2018-05-12

    Campylobacters are an unwelcome member of the poultry gut microbiota in terms of food safety. The objective of this study was to compare the microbiota, inflammatory responses, and zootechnical parameters of broiler chickens not exposed to Campylobacter jejuni with those exposed either early at 6 days old or at the age commercial broiler chicken flocks are frequently observed to become colonized at 20 days old. Birds infected with Campylobacter at 20 days became cecal colonized within 2 days of exposure, whereas birds infected at 6 days of age did not show complete colonization of the sample cohort until 9 days post-infection. All birds sampled thereafter were colonized until the end of the study at 35 days (mean 6.1 log 10 CFU per g of cecal contents). The cecal microbiota of birds infected with Campylobacter were significantly different to age-matched non-infected controls at 2 days post-infection, but generally, the composition of the cecal microbiota were more affected by bird age as the time post infection increased. The effects of Campylobacter colonization on the cecal microbiota were associated with reductions in the relative abundance of OTUs within the taxonomic family Lactobacillaceae and the Clostridium cluster XIVa. Specific members of the Lachnospiraceae and Ruminococcaceae families exhibit transient shifts in microbial community populations dependent upon the age at which the birds become colonized by C. jejuni. Analysis of ileal and cecal chemokine/cytokine gene expression revealed increases in IL-6, IL-17A, and Il-17F consistent with a Th17 response, but the persistence of the response was dependent on the stage/time of C. jejuni colonization that coincide with significant reductions in the abundance of Clostridium cluster XIVa. This study combines microbiome data, cytokine/chemokine gene expression with intestinal villus, and crypt measurements to compare chickens colonized early or late in the rearing cycle to provide insights into the

  5. The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: from current human evidence to future possibilities.

    Science.gov (United States)

    Brunkwall, Louise; Orho-Melander, Marju

    2017-06-01

    The totality of microbial genomes in the gut exceeds the size of the human genome, having around 500-fold more genes that importantly complement our coding potential. Microbial genes are essential for key metabolic processes, such as the breakdown of indigestible dietary fibres to short-chain fatty acids, biosynthesis of amino acids and vitamins, and production of neurotransmitters and hormones. During the last decade, evidence has accumulated to support a role for gut microbiota (analysed from faecal samples) in glycaemic control and type 2 diabetes. Mechanistic studies in mice support a causal role for gut microbiota in metabolic diseases, although human data favouring causality is insufficient. As it may be challenging to sort the human evidence from the large number of animal studies in the field, there is a need to provide a review of human studies. Thus, the aim of this review is to cover the current and future possibilities and challenges of using the gut microbiota, with its capacity to be modified, in the development of preventive and treatment strategies for hyperglycaemia and type 2 diabetes in humans. We discuss what is known about the composition and functionality of human gut microbiota in type 2 diabetes and summarise recent evidence of current treatment strategies that involve, or are based on, modification of gut microbiota (diet, probiotics, metformin and bariatric surgery). We go on to review some potential future gut-based glucose-lowering approaches involving microbiota, including the development of personalised nutrition and probiotic approaches, identification of therapeutic components of probiotics, targeted delivery of propionate in the proximal colon, targeted delivery of metformin in the lower gut, faecal microbiota transplantation, and the incorporation of genetically modified bacteria that express therapeutic factors into microbiota. Finally, future avenues and challenges for understanding the interplay between human nutrition, genetics

  6. Gut microbiome composition in lean patients with NASH is associated with liver damage independent of caloric intake: A prospective pilot study.

    Science.gov (United States)

    Duarte, S M B; Stefano, J T; Miele, L; Ponziani, F R; Souza-Basqueira, M; Okada, L S R R; de Barros Costa, F G; Toda, K; Mazo, D F C; Sabino, E C; Carrilho, F J; Gasbarrini, A; Oliveira, C P

    2018-04-01

    The aim of the study was to compare the gut microbiomes from obese and lean patients with or without NASH to outline phenotypic differences. We performed a cross-sectional pilot study comprising biopsy-proven NASH patients grouped according to BMI. Microbiome DNA was extracted from stool samples, and PCR amplification was performed using primers for the V4 region of the 16S rRNA gene. The amplicons were sequenced using the Ion PGM Torrent platform, and data were analyzed using QIIME software. Macronutrient consumption was analyzed by a 7-day food record. Liver fibrosis ≥ F2 was associated with increased abundance of Lactobacilli (p = 0.0007). NASH patients showed differences in Faecalibacterium, Ruminococcus, Lactobacillus and Bifidobacterium abundance compared with the control group. Lean NASH patients had a 3-fold lower abundance of Faecalibacterium and Ruminococcus (p = 0.004), obese NASH patients were enriched in Lactobacilli (p = 0.002), and overweight NASH patients had reduced Bifidobacterium (p = 0.018). Moreover, lean NASH patients showed a deficiency in Lactobacillus compared with overweight and obese NASH patients. This group also appeared similar to the control group with regard to gut microbiome alpha diversity. Although there were qualitative differences between lean NASH and overweight/obese NASH, they were not statistically significant (p = 0.618). The study limitations included a small sample size, a food questionnaire that collected only qualitative and semi-quantitative data, and variations in group gender composition that may influence differences in FXR signaling, bile acids metabolism and the composition of gut microbiota. Our preliminary finding of a different pathogenetic process in lean NASH patients needs to be confirmed by larger studies, including those with patient populations stratified by sex and dietary habits. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the

  7. Resistant starch alters gut microbiome and metabolomics profiles concurrent with amelioration of chronic kidney disease in rats

    Science.gov (United States)

    Patients and animals with chronic kidney disease (CKD) exhibit profound alterations in the gut environment including shifts in microbial composition, increased fecal pH, and increased blood levels of gut microbe-derived metabolites (xeno-metabolites). The fermentable dietary fiber—high amylose maize...

  8. Intestinal Barrier Function and the Gut Microbiome Are Differentially Affected in Mice Fed a Western-Style Diet or Drinking Water Supplemented with Fructose.

    Science.gov (United States)

    Volynets, Valentina; Louis, Sandrine; Pretz, Dominik; Lang, Lisa; Ostaff, Maureen J; Wehkamp, Jan; Bischoff, Stephan C

    2017-05-01

    Background: The consumption of a Western-style diet (WSD) and high fructose intake are risk factors for metabolic diseases. The underlying mechanisms are largely unclear. Objective: To unravel the mechanisms by which a WSD and fructose promote metabolic disease, we investigated their effects on the gut microbiome and barrier function. Methods: Adult female C57BL/6J mice were fed a sugar- and fat-rich WSD or control diet (CD) for 12 wk and given access to tap water or fructose-supplemented water. The microbiota was analyzed with the use of 16S rRNA gene sequencing. Barrier function was studied with the use of permeability tests, and endotoxin, mucus thickness, and gene expressions were measured. Results: The WSD increased body weight gain but not endotoxin translocation compared with the CD. In contrast, high fructose intake increased endotoxin translocation 2.6- and 3.8-fold in the groups fed the CD + fructose and WSD + fructose, respectively, compared with the CD group. The WSD + fructose treatment also induced a loss of mucus thickness in the colon (-46%) and reduced defensin expression in the ileum and colon. The lactulose:mannitol ratio in the WSD + fructose mice was 1.8-fold higher than in the CD mice. Microbiota analysis revealed that fructose, but not the WSD, increased the Firmicutes:Bacteroidetes ratio by 88% for CD + fructose and 63% for WSD + fructose compared with the CD group. Bifidobacterium abundance was greater in the WSD mice than in the CD mice (63-fold) and in the WSD + fructose mice than in the CD + fructose mice (330-fold). Conclusions: The consumption of a WSD or high fructose intake differentially affects gut permeability and the microbiome. Whether these differences are related to the distinct clinical outcomes, whereby the WSD primarily promotes weight gain and high fructose intake causes barrier dysfunction, needs to be investigated in future studies. © 2017 American Society for Nutrition.

  9. Nonclinical Safety Assessment of SYN-004: An Oral β-lactamase for the Protection of the Gut Microbiome From Disruption by Biliary-Excreted, Intravenously Administered Antibiotics.

    Science.gov (United States)

    Kokai-Kun, John F; Bristol, J Andrew; Setser, John; Schlosser, Michael

    2016-05-01

    SYN-004 is a first in class, recombinant β-lactamase that degrades β-lactam antibiotics and has been formulated to be administered orally to patients receiving intravenous β-lactam antibiotics including cephalosporins. SYN-004 is intended to degrade unmetabolized antibiotics excreted into the intestines and thus has the potential to protect the gut microbiome from disruption by these antibiotics. Protection of the gut microbiome is expected to protect against opportunistic enteric infections such as Clostridium difficile infection as well as antibiotic-associated diarrhea. In order to demonstrate that oral SYN-004 is safe for human clinical trials, 2 Good Laboratory Practice-compliant toxicity studies were conducted in Beagle dogs. In both studies, SYN-004 was administered orally 3 times per day up to the maximum tolerated dose of the formulation. In the first study, doses of SYN-004 administered over 28 days were safe and well tolerated in dogs with the no-observed-adverse-effect level at the high dose of 57 mg/kg/day. Systemic absorption of SYN-004 was minimal and sporadic and showed no accumulation during the study. In the second study, doses up to 57 mg/kg/day were administered to dogs in combination with an intravenous dose of ceftriaxone (300 mg/kg) given once per day for 14 days. Coadministration of oral SYN-004 with intravenous ceftriaxone was safe and well tolerated, with SYN-004 having no noticeable effect on the plasma pharmacokinetics of ceftriaxone. These preclinical studies demonstrate that SYN-004 is well tolerated and, when coadministered with ceftriaxone, does not interfere with its systemic pharmacokinetics. These data supported advancing SYN-004 into human clinical trials. © The Author(s) 2015.

  10. High-intensity sweetener consumption and gut microbiome content and predicted gene function in a cross-sectional study of adults in the United States.

    Science.gov (United States)

    Frankenfeld, Cara L; Sikaroodi, Masoumeh; Lamb, Evan; Shoemaker, Sarah; Gillevet, Patrick M

    2015-10-01

    To evaluate gut microbiome in relation to recent high-intensity sweetener consumption in healthy adults. Thirty-one adults completed a four-day food record and provided a fecal sample on the fifth day. Bacterial community in the samples was analyzed using multitag pyrosequencing. Across consumers and nonconsumers of aspartame and acesulfame-K, bacterial abundance was compared using nonparametric statistics, and bacterial diversity was compared using UniFrac analysis. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict mean relative abundance of gene function. There were seven aspartame consumers and seven acesulfame-K consumers. Three individuals overlapped groups, consuming both sweeteners. There were no differences in median bacterial abundance (class or order) across consumers and nonconsumers of either sweetener. Overall bacterial diversity was different across nonconsumers and consumers of aspartame (P Bacterial abundance profiles and predicted gene function were not associated with recent dietary high-intensity sweetener consumption. However, bacterial diversity differed across consumers and nonconsumers. Given the increasing consumption of sweeteners and the role that the microbiome may have in chronic disease outcomes, work in further studies is warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Relevance of gut microbiome and endogenous phosphatases on phytate breakdown in poultry – implications on phosphorus utilisation

    DEFF Research Database (Denmark)

    Jozefiak, D; Engberg, Ricarda Greuel; Ptak, A

    2016-01-01

    Gastrointestinal microbiota of the poultry is still relatively unexplored area. Most of the research has been conducted on broiler chickens with very few studies showing phytate-microbiome interactions. Incorporation of novel techniques in microbiology particularly, pyrosequencing should clarify...... to inhibited. In conclusion, poultry GIT microbiota can utilize 10-25% of dietary phytate. Phytase supplementation significantly affects the microbiome but the mode of action is mainly indirect, through changes in the buffering capacity of the digesta and release of IP6 isomers as well as myo-inositol....

  12. Gut microbiome composition and metabolomic profiles of wild western lowland gorillas (Gorilla gorilla gorilla) reflect host ecology

    Czech Academy of Sciences Publication Activity Database

    Gomez, A.; Petrželková, Klára Judita; Yeoman, C. J.; Vlčková, K.; Mrázek, Jakub; Koppová, Ingrid; Carbonero, F.; Ulanov, A.; Modrý, D.; Todd, A.; Torralba, M.; Nelson, K.; Gaskins, H. R.; Wilson, B.; Stumpf, R. M.; White, B. A.; Leigh, S. R.

    2015-01-01

    Roč. 24, č. 10 (2015), s. 2551-2565 ISSN 0962-1083 R&D Projects: GA ČR GA206/09/0927 Institutional support: RVO:68081766 ; RVO:67985904 Keywords : western lowland gorillas * microbiome * metabolomics * foraging ecology * anthropogenic interactions Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 5.947, year: 2015

  13. Gut microbiome composition and metabolomic profiles/nof wild western lowland gorillas (Gorilla gorilla gorilla)/nreflect host ecology

    Czech Academy of Sciences Publication Activity Database

    Gomez, A.; Petrželková, Klára Judita; Yeoman, C. J.; Vlčková, K.; Mrázek, J.; Koppova, I.; Carbonero, F.; Ulanov, A.; Modrý, David; Todd, A.; Torralba, M.; Nelson, K. E.; Gaskins, H. R.; Wilson, B.; Stumpf, R. M.; White, B. A.; Leigh, S. R.

    2015-01-01

    Roč. 24, č. 10 (2015), s. 2551-2565 ISSN 0962-1083 R&D Projects: GA ČR GA206/09/0927 Institutional support: RVO:60077344 Keywords : anthropogenic interactions * foraging ecology * metabolomics * microbiome * western lowland gorillas Subject RIV: EG - Zoology Impact factor: 5.947, year: 2015

  14. Differential Ecological Specificity of Protist and Bacterial Microbiomes across a Set of Termite Species

    KAUST Repository

    Waidele, Lena; Korb, Judith; Voolstra, Christian R.; Kü nzel, Sven; Dedeine, Franck; Staubach, Fabian

    2017-01-01

    The gut microbiome of lower termites comprises protists and bacteria that help these insects to digest cellulose and to thrive on wood. The composition of the termite gut microbiome correlates with phylogenetic distance of the animal host and host

  15. Chondriotin sulfate disaccharides as a bioactive compound modified the murine gut microbiome under healthy and stressed conditions

    Science.gov (United States)

    Chondriotin sulfate (CS) has been widely used for medical and nutraceutical purposes due to its roles in maintaining tissue structural integrity. We investigated if CS disaccharides may act as a bioactive compound and modulate gut microbial composition in mice. Our data show that CS disaccharides su...

  16. Dietary intervention modulates the gut microbiome and improves insulin resistance - a randomized controlled trial in obese postmenopausal women

    DEFF Research Database (Denmark)

    K. Brahe, Lena; Le Chatelier, Emmanuelle; Prifti, Edi

    2015-01-01

    -forming units), flaxseed mucilage (10 g) or placebo. Quantitative metagenomic analysis of faecal DNA was performed to identify the changes in the gut microbiota. Diet-induced changes in metabolic markers were explored using adjusted linear regression models. The intake of flaxseed mucilage over 6 weeks led...

  17. pH of Drinking Water Influences the Composition of Gut Microbiome and Type 1 Diabetes Incidence

    Science.gov (United States)

    Sofi, M. Hanief; Gudi, Radhika; Karumuthil-Melethil, Subha; Perez, Nicolas; Johnson, Benjamin M.; Vasu, Chenthamarakshan

    2014-01-01

    Nonobese diabetic (NOD) mice spontaneously develop type 1 diabetes (T1D), progression of which is similar to that in humans, and therefore are widely used as a model for understanding the immunological basis of this disease. The incidence of T1D in NOD mice is influenced by the degree of cleanliness of the mouse colony and the gut microflora. In this report, we show that the T1D incidence and rate of disease progression are profoundly influenced by the pH of drinking water, which also affects the composition and diversity of commensal bacteria in the gut. Female NOD mice that were maintained on acidic pH water (AW) developed insulitis and hyperglycemia rapidly compared with those on neutral pH water (NW). Interestingly, forced dysbiosis by segmented filamentous bacteria (SFB)-positive fecal transfer significantly suppressed the insulitis and T1D incidence in mice that were on AW but not in those on NW. The 16S rDNA–targeted pyrosequencing revealed a significant change in the composition and diversity of gut flora when the pH of drinking water was altered. Importantly, autoantigen-specific T-cell frequencies in the periphery and proinflammatory cytokine response in the intestinal mucosa are significantly higher in AW-recipient mice compared with their NW counterparts. These observations suggest that pH of drinking water affects the composition of gut microflora, leading to an altered autoimmune response and T1D incidence in NOD mice. PMID:24194504

  18. Consumption of acidic water alters the gut microbiome and decreases the risk of diabetes in NOD mice.

    Science.gov (United States)

    Wolf, Kyle J; Daft, Joseph G; Tanner, Scott M; Hartmann, Riley; Khafipour, Ehsan; Lorenz, Robin G

    2014-04-01

    Infant formula and breastfeeding are environmental factors that influence the incidence of Type 1 Diabetes (T1D) as well as the acidity of newborn diets. To determine if altering the intestinal microbiome is one mechanism through which an acidic liquid plays a role in T1D, we placed non-obese diabetic (NOD)/ShiLtJt mice on neutral (N) or acidified H2O and monitored the impact on microbial composition and diabetes incidence. NOD-N mice showed an increased development of diabetes, while exhibiting a decrease in Firmicutes and an increase in Bacteroidetes, Actinobacteria, and Proteobacteria from as early as 2 weeks of age. NOD-N mice had a decrease in the levels of Foxp3 expression in CD4(+)Foxp3(+) cells, as well as decreased CD4(+)IL17(+) cells, and a lower ratio of IL17/IFNγ CD4+ T-cells. Our data clearly indicates that a change in the acidity of liquids consumed dramatically alters the intestinal microbiome, the presence of protective Th17 and Treg cells, and the incidence of diabetes. This data suggests that early dietary manipulation of intestinal microbiota may be a novel mechanism to delay T1D onset in genetically pre-disposed individuals.

  19. House dust exposure mediates gut microbiome Lactobacillus enrichment and airway immune defense against allergens and virus infection.

    Science.gov (United States)

    Fujimura, Kei E; Demoor, Tine; Rauch, Marcus; Faruqi, Ali A; Jang, Sihyug; Johnson, Christine C; Boushey, Homer A; Zoratti, Edward; Ownby, Dennis; Lukacs, Nicholas W; Lynch, Susan V

    2014-01-14

    Exposure to dogs in early infancy has been shown to reduce the risk of childhood allergic disease development, and dog ownership is associated with a distinct house dust microbial exposure. Here, we demonstrate, using murine models, that exposure of mice to dog-associated house dust protects against ovalbumin or cockroach allergen-mediated airway pathology. Protected animals exhibited significant reduction in the total number of airway T cells, down-regulation of Th2-related airway responses, as well as mucin secretion. Following dog-associated dust exposure, the cecal microbiome of protected animals was extensively restructured with significant enrichment of, amongst others, Lactobacillus johnsonii. Supplementation of wild-type animals with L. johnsonii protected them against both airway allergen challenge or infection with respiratory syncytial virus. L. johnsonii-mediated protection was associated with significant reductions in the total number and proportion of activated CD11c(+)/CD11b(+) and CD11c(+)/CD8(+) cells, as well as significantly reduced airway Th2 cytokine expression. Our results reveal that exposure to dog-associated household dust results in protection against airway allergen challenge and a distinct gastrointestinal microbiome composition. Moreover, the study identifies L. johnsonii as a pivotal species within the gastrointestinal tract capable of influencing adaptive immunity at remote mucosal surfaces in a manner that is protective against a variety of respiratory insults.

  20. Bacteria, phages and pigs: the effects of in-feed antibiotics on the microbiome at different gut locations.

    Science.gov (United States)

    Looft, Torey; Allen, Heather K; Cantarel, Brandi L; Levine, Uri Y; Bayles, Darrell O; Alt, David P; Henrissat, Bernard; Stanton, Thaddeus B

    2014-08-01

    Disturbance of the beneficial gut microbial community is a potential collateral effect of antibiotics, which have many uses in animal agriculture (disease treatment or prevention and feed efficiency improvement). Understanding antibiotic effects on bacterial communities at different intestinal locations is essential to realize the full benefits and consequences of in-feed antibiotics. In this study, we defined the lumenal and mucosal bacterial communities from the small intestine (ileum) and large intestine (cecum and colon) plus feces, and characterized the effects of in-feed antibiotics (chlortetracycline, sulfamethazine and penicillin (ASP250)) on these communities. 16S rRNA gene sequence and metagenomic analyses of bacterial membership and functions revealed dramatic differences between small and large intestinal locations, including enrichment of Firmicutes and phage-encoding genes in the ileum. The large intestinal microbiota encoded numerous genes to degrade plant cell wall components, and these genes were lacking in the ileum. The mucosa-associated ileal microbiota harbored greater bacterial diversity than the lumen but similar membership to the mucosa of the large intestine, suggesting that most gut microbes can associate with the mucosa and might serve as an inoculum for the lumen. The collateral effects on the microbiota of antibiotic-fed animals caused divergence from that of control animals, with notable changes being increases in Escherichia coli populations in the ileum, Lachnobacterium spp. in all gut locations, and resistance genes to antibiotics not administered. Characterizing the differential metabolic capacities and response to perturbation at distinct intestinal locations will inform strategies to improve gut health and food safety.

  1. Prebiotic galacto-oligosaccharides mitigate the adverse effects of iron fortification on the gut microbiome: a randomised controlled study in Kenyan infants.

    Science.gov (United States)

    Paganini, Daniela; Uyoga, Mary A; Kortman, Guus A M; Cercamondi, Colin I; Moretti, Diego; Barth-Jaeggi, Tanja; Schwab, Clarissa; Boekhorst, Jos; Timmerman, Harro M; Lacroix, Christophe; Karanja, Simon; Zimmermann, Michael B

    2017-11-01

    Iron-containing micronutrient powders (MNPs) reduce anaemia in African infants, but the current high iron dose (12.5 mg/day) may decrease gut Bifidobacteriaceae and Lactobacillaceae , and increase enteropathogens, diarrhoea and respiratory tract infections (RTIs). We evaluated the efficacy and safety of a new MNP formula with prebiotic galacto-oligosaccharides (GOS) combined with a low dose (5 mg/day) of highly bioavailable iron. In a 4-month, controlled, double-blind trial, we randomised Kenyan infants aged 6.5-9.5 months (n=155) to receive daily (1) a MNP without iron (control); (2) the identical MNP but with 5 mg iron (2.5 mg as sodium iron ethylenediaminetetraacetate and 2.5 mg as ferrous fumarate) (Fe group); or (3) the identical MNP as the Fe group but with 7.5 g GOS (FeGOS group). Anaemia decreased by ≈50% in the Fe and FeGOS groups (pgut microbiome and morbidity in African infants. NCT02118402. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  2. Adoption

    Science.gov (United States)

    ... a relative, foster parent, or a completely new family. An adoptive family might be a single parent, a couple, or ... doesn't mean they don't love their adoptive family or feel close to them. This curiosity, which ...

  3. Urban Diets Linked to Gut Microbiome and Metabolome Alterations in Children: A Comparative Cross-Sectional Study in Thailand

    Directory of Open Access Journals (Sweden)

    Juma Kisuse

    2018-06-01

    Full Text Available Loss of traditional diets by food globalization may have adverse impact on the health of human being through the alteration of gut microbial ecosystem. To address this notion, we compared the gut microbiota of urban (n = 17 and rural (n = 28 school-aged children in Thailand in association with their dietary habits. Dietary records indicated that children living in urban Bangkok tended to consume modern high-fat diets, whereas children in rural Buriram tended to consume traditional vegetable-based diets. Sequencing of 16S rRNA genes amplified from stool samples showed that children in Bangkok have less Clostridiales and more Bacteroidales and Selenomonadales compared to children in Buriram and bacterial diversity is significantly less in Bangkok children than in Buriram children. In addition, fecal butyrate and propionate levels decreased in Bangkok children in association with changes in their gut microbial communities. Stool samples of these Thai children were classified into five metabolotypes (MTs based on their metabolome profiles, each characterized by high concentrations of short and middle chain fatty acids (MT1, n = 17, amino acids (MT2, n = 7, arginine (MT3, n = 6, amino acids, and amines (MT5, n = 8, or an overall low level of metabolites (MT4, n = 4. MT1 and MT4 mainly consisted of samples from Buriram, and MT2 and MT3 mainly consisted of samples from Bangkok, whereas MT5 contained three samples from Bangkok and five from Buriram samples. According to the profiles of microbiota and diets, MT1 and MT2 are characteristic of children in Buriram and Bangkok, respectively. Predicted metagenomics indicated the underrepresentation in MT2 of eight genes involved in pathways of butyrate biosynthesis, notably including paths from glutamate as well as pyruvate. Taken together, this study shows the benefit of high-vegetable Thai traditional diets on gut microbiota and suggests that high-fat and less-vegetable urban dietary habits alter gut

  4. Interactions between Obesity Status and Dietary Intake of Monounsaturated and Polyunsaturated Oils on Human Gut Microbiome Profiles in the Canola Oil Multicenter Intervention Trial (COMIT

    Directory of Open Access Journals (Sweden)

    Shuaihua Pu

    2016-10-01

    Full Text Available Long-term dietary fatty acid intake is believed to induce changes in the human gut microbiome which might be associated with human health or obesity status; however, considerable debate remains regarding the most favorable ratios of fatty acids to optimize these processes. The objective of this sub-study of a double-blinded randomized crossover clinical study, the canola oil multi-center intervention trial (COMIT, was to investigate effects of five different novel oil blends fed for 30 days each on the intestinal microbiota in 25 volunteers with risk of metabolic syndrome. The 60 g treatments included three MUFA-rich diets: 1 conventional canola oil (Canola; 2 DHA-enriched high oleic canola oil (CanolaDHA; 3 high oleic canola oil (CanolaOleic; and two PUFA-rich diets: 4 a blend of corn/safflower oil (25:75 (CornSaff; and 5 a blend of flax/safflower oil (60:40 (FlaxSaff. Stool samples were collected at the end of each period. DNA was extracted and amplified for pyrosequencing. A total of 17 phyla and 187 genera were identified. While five novel oil treatments failed to alter bacterial phyla composition, obese participants produced a higher proportion of Firmicutes to Bacteroidetes than overweight or normal weight groups (P = 0.01. Similarly at the genus level, overall bacterial distribution was highly associated with subjects’ body mass index (BMI. Treatment effects were observed between MUFA- and PUFA-rich diets, with the three MUFA diets elevating Parabacteroides, Prevotella, Turicibacter, and Enterobacteriaceae (F’s populations, while the two PUFA-rich diets favored the abundance of Isobaculum. High MUFA content feedings also resulted in an increase of Parabacteroides and a decrease of Isobaculum in obese, but not overweight subjects. Data suggest that BMI is a predominant factor in characterization of human gut microbiota profiles, and that MUFA-rich and PUFA-rich diets impact the composition of gut microbiota at lower taxonomical levels

  5. Next generation sequencing for gut microbiome characterization in rainbow trout (Oncorhynchus mykiss) fed animal by-product meals as an alternative to fishmeal protein sources.

    Science.gov (United States)

    Rimoldi, Simona; Terova, Genciana; Ascione, Chiara; Giannico, Riccardo; Brambilla, Fabio

    2018-01-01

    Animal by-product meals from the rendering industry could provide a sustainable and commercially viable alternative to fishmeal (FM) in aquaculture, as they are rich in most essential amino acids and contain important amounts of water-soluble proteins that improve feed digestibility and palatability. Among them, poultry by-product meal (PBM) have given encouraging results in rainbow trout (Oncorhynchus mykiss). However, the introduction of new ingredients in the diet needs to be carefully evaluated since diet is one of the main factors affecting the gut microbiota, which is a complex community that contributes to host metabolism, nutrition, growth, and disease resistance. Accordingly, we investigated the effects of partial replacement of dietary FM with a mix of animal by-product meals and plant proteins on intestinal microbiota composition of rainbow trout in relation to growth and feeding efficiency parameters. We used 1540 trout with an initial mean body weight of 94.6 ± 14.2 g. Fish were fed for 12 weeks with 7 different feed formulations. The growth data showed that trout fed on diets rich in animal by-product meals grew as well as fish fed on control diet, which was rich in FM (37.3%) and PBM-free. High-throughput 16S rRNA gene amplicon sequencing (MiSeq platform, Illumina) was utilised to study the gut microbial community profile. After discarding Cyanobacteria (class Chloroplast) and mitochondria reads a total of 2,701,274 of reads taxonomically classified, corresponding to a mean of 96,474 ± 68,056 reads per sample, were obtained. Five thousand three hundred ninety-nine operational taxonomic units (OTUs) were identified, which predominantly mapped to the phyla of Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria. The ratio between vegetable and animal proteins proved to play a central role in determining microbiome profiles and Firmicutes and Proteobacteria phyla were particularly discriminatory for diet type in trout. Plant ingredients

  6. Next generation sequencing for gut microbiome characterization in rainbow trout (Oncorhynchus mykiss) fed animal by-product meals as an alternative to fishmeal protein sources

    Science.gov (United States)

    Rimoldi, Simona; Ascione, Chiara; Giannico, Riccardo; Brambilla, Fabio

    2018-01-01

    Animal by-product meals from the rendering industry could provide a sustainable and commercially viable alternative to fishmeal (FM) in aquaculture, as they are rich in most essential amino acids and contain important amounts of water-soluble proteins that improve feed digestibility and palatability. Among them, poultry by-product meal (PBM) have given encouraging results in rainbow trout (Oncorhynchus mykiss). However, the introduction of new ingredients in the diet needs to be carefully evaluated since diet is one of the main factors affecting the gut microbiota, which is a complex community that contributes to host metabolism, nutrition, growth, and disease resistance. Accordingly, we investigated the effects of partial replacement of dietary FM with a mix of animal by-product meals and plant proteins on intestinal microbiota composition of rainbow trout in relation to growth and feeding efficiency parameters. We used 1540 trout with an initial mean body weight of 94.6 ± 14.2 g. Fish were fed for 12 weeks with 7 different feed formulations. The growth data showed that trout fed on diets rich in animal by-product meals grew as well as fish fed on control diet, which was rich in FM (37.3%) and PBM-free. High-throughput 16S rRNA gene amplicon sequencing (MiSeq platform, Illumina) was utilised to study the gut microbial community profile. After discarding Cyanobacteria (class Chloroplast) and mitochondria reads a total of 2,701,274 of reads taxonomically classified, corresponding to a mean of 96,474 ± 68,056 reads per sample, were obtained. Five thousand three hundred ninety-nine operational taxonomic units (OTUs) were identified, which predominantly mapped to the phyla of Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria. The ratio between vegetable and animal proteins proved to play a central role in determining microbiome profiles and Firmicutes and Proteobacteria phyla were particularly discriminatory for diet type in trout. Plant ingredients

  7. Next generation sequencing for gut microbiome characterization in rainbow trout (Oncorhynchus mykiss fed animal by-product meals as an alternative to fishmeal protein sources.

    Directory of Open Access Journals (Sweden)

    Simona Rimoldi

    Full Text Available Animal by-product meals from the rendering industry could provide a sustainable and commercially viable alternative to fishmeal (FM in aquaculture, as they are rich in most essential amino acids and contain important amounts of water-soluble proteins that improve feed digestibility and palatability. Among them, poultry by-product meal (PBM have given encouraging results in rainbow trout (Oncorhynchus mykiss. However, the introduction of new ingredients in the diet needs to be carefully evaluated since diet is one of the main factors affecting the gut microbiota, which is a complex community that contributes to host metabolism, nutrition, growth, and disease resistance. Accordingly, we investigated the effects of partial replacement of dietary FM with a mix of animal by-product meals and plant proteins on intestinal microbiota composition of rainbow trout in relation to growth and feeding efficiency parameters. We used 1540 trout with an initial mean body weight of 94.6 ± 14.2 g. Fish were fed for 12 weeks with 7 different feed formulations. The growth data showed that trout fed on diets rich in animal by-product meals grew as well as fish fed on control diet, which was rich in FM (37.3% and PBM-free. High-throughput 16S rRNA gene amplicon sequencing (MiSeq platform, Illumina was utilised to study the gut microbial community profile. After discarding Cyanobacteria (class Chloroplast and mitochondria reads a total of 2,701,274 of reads taxonomically classified, corresponding to a mean of 96,474 ± 68,056 reads per sample, were obtained. Five thousand three hundred ninety-nine operational taxonomic units (OTUs were identified, which predominantly mapped to the phyla of Firmicutes, Proteobacteria, Bacteroidetes and Actinobacteria. The ratio between vegetable and animal proteins proved to play a central role in determining microbiome profiles and Firmicutes and Proteobacteria phyla were particularly discriminatory for diet type in trout. Plant

  8. The intestinal microbiome of fish under starvation

    OpenAIRE

    Xia, Jun Hong; Lin, Grace; Fu, Gui Hong; Wan, Zi Yi; Lee, May; Wang, Le; Liu, Xiao Jun; Yue, Gen Hua

    2014-01-01

    Background Starvation not only affects the nutritional and health status of the animals, but also the microbial composition in the host’s intestine. Next-generation sequencing provides a unique opportunity to explore gut microbial communities and their interactions with hosts. However, studies on gut microbiomes have been conducted predominantly in humans and land animals. Not much is known on gut microbiomes of aquatic animals and their changes under changing environmental conditions. To add...

  9. Captivity humanizes the primate microbiome.

    Science.gov (United States)

    Clayton, Jonathan B; Vangay, Pajau; Huang, Hu; Ward, Tonya; Hillmann, Benjamin M; Al-Ghalith, Gabriel A; Travis, Dominic A; Long, Ha Thang; Tuan, Bui Van; Minh, Vo Van; Cabana, Francis; Nadler, Tilo; Toddes, Barbara; Murphy, Tami; Glander, Kenneth E; Johnson, Timothy J; Knights, Dan

    2016-09-13

    The primate gastrointestinal tract is home to trillions of bacteria, whose composition is associated with numerous metabolic, autoimmune, and infectious human diseases. Although there is increasing evidence that modern and Westernized societies are associated with dramatic loss of natural human gut microbiome diversity, the causes and consequences of such loss are challenging to study. Here we use nonhuman primates (NHPs) as a model system for studying the effects of emigration and lifestyle disruption on the human gut microbiome. Using 16S rRNA gene sequencing in two model NHP species, we show that although different primate species have distinctive signature microbiota in the wild, in captivity they lose their native microbes and become colonized with Prevotella and Bacteroides, the dominant genera in the modern human gut microbiome. We confirm that captive individuals from eight other NHP species in a different zoo show the same pattern of convergence, and that semicaptive primates housed in a sanctuary represent an intermediate microbiome state between wild and captive. Using deep shotgun sequencing, chemical dietary analysis, and chloroplast relative abundance, we show that decreasing dietary fiber and plant content are associated with the captive primate microbiome. Finally, in a meta-analysis including published human data, we show that captivity has a parallel effect on the NHP gut microbiome to that of Westernization in humans. These results demonstrate that captivity and lifestyle disruption cause primates to lose native microbiota and converge along an axis toward the modern human microbiome.

  10. Expression of arsenic resistance genes in the obligate anaerobe Bacteroides vulgatus ATCC 8482, a gut microbiome bacterium

    OpenAIRE

    Li, Jiaojiao; Mandal, Goutam; Rosen, Barry P.

    2016-01-01

    The response of the obligate anaerobe Bacteroides vulgatus ATCC 8482, a common human gut microbiota, to arsenic was determined. B. vulgatus ATCC 8482 is highly resistant to pentavalent As(V) and methylarsenate (MAs(V)). It is somewhat more sensitive to trivalent inorganic As(III) but 100-fold more sensitive to methylarsenite (MAs(III)) than to As(III). B. vulgatus ATCC 8482 has eight continuous genes in its genome that we demonstrate form an arsenical-inducible transcriptional unit. The first...

  11. Metagenomic characterization of the effect of feed additives on the gut microbiome and antibiotic resistome of feedlot cattle.

    Science.gov (United States)

    Thomas, Milton; Webb, Megan; Ghimire, Sudeep; Blair, Amanda; Olson, Kenneth; Fenske, Gavin John; Fonder, Alex Thomas; Christopher-Hennings, Jane; Brake, Derek; Scaria, Joy

    2017-09-25

    In North America, antibiotic feed additives such as monensin and tylosin are added to the finishing diets of feedlot cattle to counter the ill-effects of feeding diets with rapidly digestible carbohydrates. While these feed additives have been proven to improve feed efficiency and reduce liver abscess incidence, how these products impact the gastrointestinal microbiota is not completely understood. In this study, we analyzed the impact of providing antibiotic feed additives to feedlot cattle using metagenome sequencing of treated and control animals. Our results indicate that use of antibiotic feed additives does not produce discernable changes at the phylum level. However, treated cattle had reduced abundance of gram-positive bacteria at the genus level. The abundance of Ruminococcus, Erysipelotrichaceae and Lachnospiraceae in the gut of treated steers was reduced. Functional analysis of the data indicates that there was only minimal impact due to the treatment in the rumen. Genes involved in detoxification were significantly increased in the rumen of AB steers. But the relative abundance of these genes was < 0.3%. However, our results did not show any correlation between the presence of antimicrobial resistance genes in the gut microbiota and the administration of antibiotic feed additives.

  12. MALDI-TOF identification of the human Gut microbiome in people with and without diarrhea in Senegal.

    Directory of Open Access Journals (Sweden)

    Bissoume Samb-Ba

    Full Text Available BACKGROUND: In Africa, there are several problems with the specific identification of bacteria. Recently, MALDI-TOF mass spectrometry has become a powerful tool for the routine microbial identification in many clinical laboratories. METHODOLOGY/PRINCIPAL FINDINGS: This study was conducted using feces from 347 individuals (162 with diarrhea and 185 without diarrhea sampled in health centers in Dakar, Senegal. Feces were transported from Dakar to Marseille, France, where they were cultured using different culture conditions. The isolated colonies were identified using MALDI-TOF. If a colony was unidentified, 16S rRNA sequencing was performed. Overall, 2,753 isolates were tested, allowing for the identification of 189 bacteria from 5 phyla, including 2 previously unknown species, 11 species not previously reported in the human gut, 10 species not previously reported in humans, and 3 fungi. 2,718 bacterial isolates (98.8% out of 2,750 yielded an accurate identification using mass spectrometry, as did the 3 Candida albicans isolates. Thirty-two bacterial isolates not identified by MALDI-TOF (1.2% were identified by sequencing, allowing for the identification of 2 new species. The number of bacterial species per fecal sample was significantly higher among patients without diarrhea (8.6±3 than in those with diarrhea (7.3±3.4; P = 0.0003. A modification of the gut microbiota was observed between the two groups. In individuals with diarrhea, major commensal bacterial species such as E. coli were significantly decreased (85% versus 64%, as were several Enterococcus spp. (E. faecium and E. casseliflavus and anaerobes, such as Bacteroides spp. (B. uniformis and B. vulgatus and Clostridium spp. (C. bifermentans, C. orbiscindens, C. perfringens, and C. symbosium. Conversely, several Bacillus spp. (B. licheniformis, B. mojavensis, and B. pumilus were significantly more frequent among patients with diarrhea. CONCLUSIONS/SIGNIFICANCE: MALDI-TOF is a

  13. Immunological and Clinical Effect of Diet Modulation of the Gut Microbiome in Multiple Sclerosis Patients: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Marina Saresella

    2017-10-01

    Full Text Available Pathogenesis of autoimmune disorders, including multiple sclerosis (MS, has been linked to an alteration of the resident microbial commensal community and of the interplay between the microbiota and the immune system. Dietary components such as fiber, acting on microbiota composition, could, in principle, result in immune modulation and, thus, could be used to obtain beneficial outcomes for patients. We verified this hypothesis in a pilot study involving two groups of clinically similar relapsing-remitting (RR MS patients who had undergone either a high-vegetable/low-protein diet (HV/LP diet group; N = 10 or a “Western Diet” (WD group; N = 10 for at least 12 months. Gut microbiota composition, analyzed by 16 S V4 rRNA gene sequencing and immunological profiles, was examined after a minimum of 12 months of diet. Results showed that, in the HV/LP diet group compared to the WD group: (1 Lachnospiraceae family was significantly more abundant; (2 IL-17-producing T CD4+ lymphocytes (p = 0.04 and PD-1 expressing T CD4+ lymphocytes (p = 0.0004 were significantly decreased; and (3 PD-L1 expressing monocytes (p = 0.009 were significantly increased. In the HV/LP diet group, positive correlations between Lachnospiraceae and both CD14+/IL-10+ and CD14+/TGFβ+monocytes (RSp = 0.707, p = 0.05, and RSp = 0.73, p = 0.04, respectively, as well as between Lachnospiraceae and CD4+/CD25+/FoxP3+ T lymphocytes (RSp = 0.68, p = 0.02 were observed. Evaluation of clinical parameters showed that in the HV/LP diet group alone the relapse rate during the 12 months follow-up period and the Expanded Disability Status Scale score at the end of the study period were significantly reduced. Diet modulates dysbiosis and improves clinical parameters in MS patients by increasing anti-inflammatory circuits. Because Lachnospiraceae favor Treg differentiation as well as TGFβ and IL-10 production this effect could be associated

  14. The role of microbiome in central nervous system disorders

    Science.gov (United States)

    Wang, Yan; Kasper, Lloyd H.

    2014-01-01

    Mammals live in a co-evolutionary association with the plethora of microorganisms that reside at a variety of tissue microenvironments. The microbiome represents the collective genomes of these co-existing microorganisms, which is shaped by host factors such as genetics and nutrients but in turn is able to influence host biology in health and disease. Niche-specific microbiome, prominently the gut microbiome, has the capacity to effect both local and distal sites within the host. The gut microbiome has played a crucial role in the bidirectional gut-brain axis that integrates the gut and central nervous system (CNS) activities, and thus the concept of microbiome-gut-brain axis is emerging. Studies are revealing how diverse forms of neuro-immune and neuro-psychiatric disorders are correlated with or modulated by variations of microbiome, microbiota-derived products and exogenous antibiotics and probiotics. The microbiome poises the peripheral immune homeostasis and predisposes host susceptibility to CNS autoimmune diseases such as multiple sclerosis. Neural, endocrine and metabolic mechanisms are also critical mediators of the microbiome-CNS signaling, which are more involved in neuro-psychiatric disorders such as autism, depression, anxiety, stress. Research on the role of microbiome in CNS disorders deepens our academic knowledge about host-microbiome commensalism in central regulation and in practicality, holds conceivable promise for developing novel prognostic and therapeutic avenues for CNS disorders. PMID:24370461

  15. Early postnatal diets affect the bioregional small intestine microbiome and ileal metabolome in neonatal piglets

    Science.gov (United States)

    Exclusive breastfeeding is known to be protective against gastrointestinal disorders and may modify gut development. Although the gut microbiome has been implicated, little is known about how early diet impacts the small intestinal microbiome, and how microbial shifts impact gut metabolic physiology...

  16. A catalog of the mouse gut metagenome

    DEFF Research Database (Denmark)

    Xiao, Liang; Feng, Qiang; Liang, Suisha

    2015-01-01

    laboratories and fed either a low-fat or high-fat diet. Similar to the human gut microbiome, >99% of the cataloged genes are bacterial. We identified 541 metagenomic species and defined a core set of 26 metagenomic species found in 95% of the mice. The mouse gut microbiome is functionally similar to its human......We established a catalog of the mouse gut metagenome comprising ∼2.6 million nonredundant genes by sequencing DNA from fecal samples of 184 mice. To secure high microbiome diversity, we used mouse strains of diverse genetic backgrounds, from different providers, kept in different housing...... counterpart, with 95.2% of its Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologous groups in common. However, only 4.0% of the mouse gut microbial genes were shared (95% identity, 90% coverage) with those of the human gut microbiome. This catalog provides a useful reference for future studies....

  17. The microbiome of New World vultures

    OpenAIRE

    Roggenbuck, Michael; Schnell, Ida Baerholm; Blom, Nikolaj; Bælum, Jacob; Bertelsen, Mads Frost; Sicheritz-Pontén, Thomas; Sørensen, Søren Johannes; Gilbert, M. Thomas P.; Graves, Gary R.; Hansen, Lars Henrik

    2014-01-01

    Vultures are scavengers that fill a key ecosystem niche, in which they have evolved a remarkable tolerance to bacterial toxins in decaying meat. Here we report the first deep metagenomic analysis of the vulture microbiome. Through face and gut comparisons of 50 vultures representing two species, we demonstrate a remarkably conserved low diversity of gut microbial flora. The gut samples contained an average of 76 operational taxonomic units (OTUs) per specimen, compared with 528 OTUs on the fa...

  18. Review: Maternal health and the placental microbiome.

    Science.gov (United States)

    Pelzer, Elise; Gomez-Arango, Luisa F; Barrett, Helen L; Nitert, Marloes Dekker

    2017-06-01

    Over the past decade, the role of the microbiome in regulating metabolism, immune function and behavior in humans has become apparent. It has become clear that the placenta is not a sterile organ, but rather has its own endogenous microbiome. The composition of the placental microbiome is distinct from that of the vagina and has been reported to resemble the oral microbiome. Compared to the gut microbiome, the placental microbiome exhibits limited microbial diversity. This review will focus on the current understanding of the placental microbiota in normal healthy pregnancy and also in disease states including preterm birth, chorioamnionitis and maternal conditions such as obesity, gestational diabetes mellitus and preeclampsia. Factors known to alter the composition of the placental microbiota will be discussed in the final part of this review. Copyright © 2016. Published by Elsevier Ltd.

  19. The functional microbiome of arthropods.

    Science.gov (United States)

    Degli Esposti, Mauro; Martinez Romero, Esperanza

    2017-01-01

    Many studies on the microbiome of animals have been reported but a comprehensive analysis is lacking. Here we present a meta-analysis on the microbiomes of arthropods and their terrestrial habitat, focusing on the functional profile of bacterial communities derived from metabolic traits that are essential for microbial life. We report a detailed analysis of probably the largest set of biochemically defined functional traits ever examined in microbiome studies. This work deals with the phylum proteobacteria, which is usually dominant in marine and terrestrial environments and covers all functions associated with microbiomes. The considerable variation in the distribution and abundance of proteobacteria in microbiomes has remained fundamentally unexplained. This analysis reveals discrete functional groups characteristic for adaptation to anaerobic conditions, which appear to be defined by environmental filtering of taxonomically related taxa. The biochemical diversification of the functional groups suggests an evolutionary trajectory in the structure of arthropods' microbiome, from metabolically versatile to specialized proteobacterial organisms that are adapted to complex environments such as the gut of social insects. Bacterial distribution in arthropods' microbiomes also shows taxonomic clusters that do not correspond to functional groups and may derive from other factors, including common contaminants of soil and reagents.

  20. Healthy human gut phageome

    NARCIS (Netherlands)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T.; Oost, van der John; Vos, de Willem M.; Young, Mark J.

    2016-01-01

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of

  1. Anaerobic 4-hydroxyproline utilization: Discovery of a new glycyl radical enzyme in the human gut microbiome uncovers a widespread microbial metabolic activity.

    Science.gov (United States)

    Huang, Yolanda Y; Martínez-Del Campo, Ana; Balskus, Emily P

    2018-02-06

    The discovery of enzymes responsible for previously unappreciated microbial metabolic pathways furthers our understanding of host-microbe and microbe-microbe interactions. We recently identified and characterized a new gut microbial glycyl radical enzyme (GRE) responsible for anaerobic metabolism of trans-4-hydroxy-l-proline (Hyp). Hyp dehydratase (HypD) catalyzes the removal of water from Hyp to generate Δ 1 -pyrroline-5-carboxylate (P5C). This enzyme is encoded in the genomes of a diverse set of gut anaerobes and is prevalent and abundant in healthy human stool metagenomes. Here, we discuss the roles HypD may play in different microbial metabolic pathways as well as the potential implications of this activity for colonization resistance and pathogenesis within the human gut. Finally, we present evidence of anaerobic Hyp metabolism in sediments through enrichment culturing of Hyp-degrading bacteria, highlighting the wide distribution of this pathway in anoxic environments beyond the human gut.

  2. Gene expression profiling gut microbiota in different races of humans

    Science.gov (United States)

    Chen, Lei; Zhang, Yu-Hang; Huang, Tao; Cai, Yu-Dong

    2016-03-01

    The gut microbiome is shaped and modified by the polymorphisms of microorganisms in the intestinal tract. Its composition shows strong individual specificity and may play a crucial role in the human digestive system and metabolism. Several factors can affect the composition of the gut microbiome, such as eating habits, living environment, and antibiotic usage. Thus, various races are characterized by different gut microbiome characteristics. In this present study, we studied the gut microbiomes of three different races, including individuals of Asian, European and American races. The gut microbiome and the expression levels of gut microbiome genes were analyzed in these individuals. Advanced feature selection methods (minimum redundancy maximum relevance and incremental feature selection) and four machine-learning algorithms (random forest, nearest neighbor algorithm, sequential minimal optimization, Dagging) were employed to capture key differentially expressed genes. As a result, sequential minimal optimization was found to yield the best performance using the 454 genes, which could effectively distinguish the gut microbiomes of different races. Our analyses of extracted genes support the widely accepted hypotheses that eating habits, living environments and metabolic levels in different races can influence the characteristics of the gut microbiome.

  3. Food Design to Feed the Human Gut Microbiota

    NARCIS (Netherlands)

    Ercolini, Danilo; Fogliano, Vincenzo

    2018-01-01

    The gut microbiome has an enormous impact on the life of the host, and the diet plays a fundamental role in shaping microbiome composition and function. The way food is processed is a key factor determining the amount and type of material reaching the gut bacteria and influencing their growth and

  4. Proceedings of the 2013 A.S.P.E.N. Research workshop: the interface between nutrition and the gut microbiome: implications and applications for human health [corrected].

    Science.gov (United States)

    Alverdy, John; Gilbert, Jack; DeFazio, Jennifer R; Sadowsky, Michael J; Chang, Eugene B; Morowitz, Michael J; Teitelbaum, Daniel H

    2014-02-01

    The human and earth microbiomes are among the most important biological agents in understanding and preventing disease. Technology is advancing at a fast pace and allowing for high-resolution analysis of the composition and function of our microbial partners across regions, space, and time. Bioinformaticists and biostatisticians are developing ever more elegant displays to understand the generated megadatasets. A virtual cyberinfrastructure of search engines to cross-reference the rapidly developing data is emerging in line with technologic advances. Nutrition science will reap the benefits of this new field, and its role in preserving the earth and the humans who inhabit it will become evidently clear. In this report we highlight some of the topics of an A.S.P.E.N.-sponsored symposium held during Clinical Nutrition Week in 2013 that address the importance of the human microbiome to human health and disease.

  5. Compositional and Functional Differences in the Human Gut Microbiome Correlate with Clinical Outcome following Infection with Wild-Type Salmonella enterica Serovar Typhi.

    Science.gov (United States)

    Zhang, Yan; Brady, Arthur; Jones, Cheron; Song, Yang; Darton, Thomas C; Jones, Claire; Blohmke, Christoph J; Pollard, Andrew J; Magder, Laurence S; Fasano, Alessio; Sztein, Marcelo B; Fraser, Claire M

    2018-05-08

    Insights into disease susceptibility as well as the efficacy of vaccines against typhoid and other enteric pathogens may be informed by better understanding the relationship between the effector immune response and the gut microbiota. In the present study, we characterized the composition (16S rRNA gene profiling) and function (RNA sequencing [RNA-seq]) of the gut microbiota following immunization and subsequent exposure to wild-type Salmonella enterica serovar Typhi in a human challenge model to further investigate the central hypothesis that clinical outcomes may be linked to the gut microbiota. Metatranscriptome analysis of longitudinal stool samples collected from study subjects revealed two stable patterns of gene expression for the human gut microbiota, dominated by transcripts from either Methanobrevibacter or a diverse representation of genera in the Firmicutes phylum. Immunization with one of two live oral attenuated vaccines against S.  Typhi had minimal effects on the composition or function of the gut microbiota. It was observed that subjects harboring the methanogen-dominated transcriptome community at baseline displayed a lower risk of developing symptoms of typhoid following challenge with wild-type S.  Typhi. Furthermore, genes encoding antioxidant proteins, metal homeostasis and transport proteins, and heat shock proteins were expressed at a higher level at baseline or after challenge with S.  Typhi in subjects who did not develop symptoms of typhoid. These data suggest that functional differences relating to redox potential and ion homeostasis in the gut microbiota may impact clinical outcomes following exposure to wild-type S.  Typhi. IMPORTANCE S.  Typhi is a significant cause of systemic febrile morbidity in settings with poor sanitation and limited access to clean water. It has been demonstrated that the human gut microbiota can influence mucosal immune responses, but there is little information available on the impact of the human gut

  6. [A machine learning model using gut microbiome data for predicting changes of trimethylamine-N-oxide in healthy volunteers after choline consumption].

    Science.gov (United States)

    Lu, Jun-Qi; Wang, Shan; Yin, Jia; Wu, Shan; He, Yan; Zheng, Hui-Min; Sheng, Hua-Fang; Zhou, Hong-Wei

    2017-03-20

    To establish a machine learning model based on gut microbiota for predicting the level of trimethylamine N-oxide (TMAO) metabolism in vivo after choline intake to provide guidance of individualized precision diet and evidence for screening population at high risks of cardiovascular disease. We quantified plasma levels of TMAO in 18 healthy volunteers before and 8 h after a choline challenge (ingestion of two boiled eggs). The volunteers were divided into two groups with increased or decreased TMAO level following choline challenge. Fresh fecal samples were collected before taking fasting blood samples for amplifying 16S rRNA V4 tags, and the PCR products were sequenced using the platform of Illumina HiSeq 2000. The differences in gut microbiata between subjects with increased and decreased plasma TMAO were analyzed using QIIME. Based on the gut microbiota data and TMAO levels in the two groups, the prediction model was established using the machine learning random forest algorithm, and the validity of the model was tested using a verified dataset. An obvious difference was found in beta diversity of the gut microbota between the subjects with increased and decreased plasma TMAO level following choline challenge. The area under the curve (AUC) of the model was 86.39% (95% CI: 72.7%-100%). Using the verified dataset, the model showed a much higher probability for correctly predicting TMAO variation following choline challenge. The model is feasible and reliable for predicting the level of TMAO metabolism in vivo based on gut microbiota.

  7. Deletion of the Toll-Like Receptor 5 Gene Per Se Does Not Determine the Gut Microbiome Profile That Induces Metabolic Syndrome: Environment Trumps Genotype.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    Full Text Available Over the past decade, emerging evidence has linked alterations in the gut microbial composition to a wide range of diseases including obesity, type 2 diabetes, and cardiovascular disease. Toll-like receptors (TLRs are the major mediators for the interactions between gut microbiota and host innate immune system, which is involved in the localization and structuring of host gut microbiota. A previous study found that TLR5 deficient mice (TLR5KO1 had altered gut microbial composition which led to the development of metabolic syndrome including hyperlipidemia, hypertension, insulin resistance and increased adiposity. In the current study, a second TLR5-deficient mouse model was studied (TLR5KO2. TLR5 deficient mice did not manifest metabolic abnormalities related to the metabolic syndrome compared with littermate controls maintained on normal chow or after feeding a high fat diet. Analysis of the gut microbial composition of littermate TLR5KO2 and wild type mice revealed no significant difference in the overall microbiota structure between genotypes. However, the TLR5KO2 microbiota was distinctly different from that previously reported for TLR5KO1 mice with metabolic syndrome. We conclude that an altered composition of the microbiota in a given environment can result in metabolic syndrome, but it is not a consequence of TLR5 deficiency per se.

  8. Randomised clinical trial: Gut microbiome biomarkers are associated with clinical response to a low FODMAP diet in children with the irritable bowel syndrome

    Science.gov (United States)

    A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet can ameliorate symptoms in adult irritable bowel syndrome (IBS) within 48 h. To determine the efficacy of a low FODMAP diet in childhood IBS and whether gut microbial composition and/or metabolic capacity ar...

  9. Marek’s Disease Virus influences the core gut microbiome of the chicken during the early and late phases of viral replication

    Science.gov (United States)

    Marek’s disease (MD) is an important neoplastic disease of chickens caused by the Marek’s disease virus (MDV), an oncogenic alphaherpesvirus. In this study, dysbiosis induced by MDV on the core gut flora of chicken was assessed using next generation sequence (NGS) analysis. Total fecal and cecum-der...

  10. Efficacy of fecal microbiota transplantation in 2 children with recurrent Clostridium difficile infection and its impact on their growth and gut microbiome.

    Science.gov (United States)

    Walia, Ritu; Garg, Shashank; Song, Yang; Girotra, Mohit; Cuffari, Carmen; Fricke, Wolfgang Florian; Dutta, Sudhir K

    2014-11-01

    Fecal microbiota transplantation (FMT) is recognized as an alternative therapeutic modality for recurrent Clostridium difficile infection (RCDI); however, data on its efficacy in children are lacking, including its effect on their growth and fecal microbiota. We report on 2 young children (gut microbiota.

  11. The role of the microbiome for human health : from basic science to clinical applications

    NARCIS (Netherlands)

    Mohajeri, M Hasan; Brummer, Robert J M; Rastall, Robert A; Weersma, Rinse K; Harmsen, Hermie J M; Faas, Marijke; Eggersdorfer, Manfred

    The 2017 annual symposium organized by the University Medical Center Groningen in The Netherlands focused on the role of the gut microbiome in human health and disease. Experts from academia and industry examined interactions of prebiotics, probiotics, or vitamins with the gut microbiome in health

  12. Next-Generation Immune Repertoire Sequencing as a Clue to Elucidate the Landscape of Immune Modulation by Host–Gut Microbiome Interactions

    Directory of Open Access Journals (Sweden)

    Tatsuo Ichinohe

    2018-04-01

    Full Text Available The human immune system is a fine network consisted of the innumerable numbers of functional cells that balance the immunity and tolerance against various endogenous and environmental challenges. Although advances in modern immunology have revealed a role of many unique immune cell subsets, technologies that enable us to capture the whole landscape of immune responses against specific antigens have been not available to date. Acquired immunity against various microorganisms including host microbiome is principally founded on T cell and B cell populations, each of which expresses antigen-specific receptors that define a unique clonotype. Over the past several years, high-throughput next-generation sequencing has been developed as a powerful tool to profile T- and B-cell receptor repertoires in a given individual at the single-cell level. Sophisticated immuno-bioinformatic analyses by use of this innovative methodology have been already implemented in clinical development of antibody engineering, vaccine design, and cellular immunotherapy. In this article, we aim to discuss the possible application of high-throughput immune receptor sequencing in the field of nutritional and intestinal immunology. Although there are still unsolved caveats, this emerging technology combined with single-cell transcriptomics/proteomics provides a critical tool to unveil the previously unrecognized principle of host–microbiome immune homeostasis. Accumulation of such knowledge will lead to the development of effective ways for personalized immune modulation through deeper understanding of the mechanisms by which the intestinal environment affects our immune ecosystem.

  13. Gut Homeostasis, Microbial Dysbiosis, and Opioids.

    Science.gov (United States)

    Wang, Fuyuan; Roy, Sabita

    2017-01-01

    Gut homeostasis plays an important role in maintaining animal and human health. The disruption of gut homeostasis has been shown to be associated with multiple diseases. The mutually beneficial relationship between the gut microbiota and the host has been demonstrated to maintain homeostasis of the mucosal immunity and preserve the integrity of the gut epithelial barrier. Currently, rapid progress in the understanding of the host-microbial interaction has redefined toxicological pathology of opioids and their pharmacokinetics. However, it is unclear how opioids modulate the gut microbiome and metabolome. Our study, showing opioid modulation of gut homeostasis in mice, suggests that medical interventions to ameliorate the consequences of drug use/abuse will provide potential therapeutic and diagnostic strategies for opioid-modulated intestinal infections. The study of morphine's modulation of the gut microbiome and metabolome will shed light on the toxicological pathology of opioids and its role in the susceptibility to infectious diseases.

  14. Short Course in the Microbiome

    Directory of Open Access Journals (Sweden)

    Kimberly Falana

    2015-07-01

    Full Text Available Over the past decade, it has become evident that the microbiome is an important environmental factor that affects many physiological processes, such as cell proliferation and differentiation, behaviour, immune function and metabolism. More importantly, it may contribute to a wide variety of diseases, including cancer, inflammatory diseases, metabolic diseases and responses to pathogens. We expect that international, integrative and interdisciplinary translational research teams, along with the emergence of FDA-approved platforms, will set the framework for microbiome-based therapeutics and diagnostics. We recognize that the microbiome ecosystem offers new promise for personalized/precision medicine and targeted treatment for a variety of diseases. The short course was held as a four-session webinar series in April 2015, taught by pioneers and experts in the microbiome ecosystem, covering a broad range of topics from the healthy microbiome to the effects of an altered microbiome from neonates to adults and the long term effects as it is related to disease, from asthma to cancer. We have learned to appreciate how beneficial our microbes are in breaking down our food, fighting off infections and nurturing our immune system, and this information provides us with ideas as to how we can manipulate our microbiome to prevent certain diseases. However, given the variety of applications, there are scientific challenges, though there are very promising areas in reference to the clinical benefits of understanding more about our microbiome, whether in our gut or on our skin: the outlook is bright. A summary of the short course is presented as a meeting dispatch.

  15. Childhood Malnutrition and the Intestinal Microbiome Malnutrition and the microbiome

    OpenAIRE

    Kane, Anne V.; Dinh, Duy M.; Ward, Honorine D.

    2014-01-01

    Malnutrition contributes to almost half of all deaths in children under the age of 5 years, particularly those who live in resource-constrained areas. Those who survive frequently suffer from long-term sequelae including growth failure and neurodevelopmental impairment. Malnutrition is part of a vicious cycle of impaired immunity, recurrent infections and worsening malnutrition. Recently, alterations in the gut microbiome have also been strongly implicated in childhood malnutrition. It has be...

  16. Understanding Microbiome Effect on Immune Checkpoint Inhibition in Lung Cancer: Placing the Puzzle Pieces Together.

    Science.gov (United States)

    Swami, Umang; Zakharia, Yousef; Zhang, Jun

    2018-05-17

    Over the past couple of years, human microbiome has received increasing attention as a regulator and predictor of response to the therapies of various diseases. It is speculated that manipulating gut microbiome can modify response to cancer immunotherapies as well. Through this review, we have critically analyzed our current understanding of gut microbiome as a modulator of immunotherapies in lung cancer, explained conflicting data, evaluated current gaps and extrapolated our present knowledge to generate directions for future investigations.

  17. Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial

    OpenAIRE

    Villar-Garc?a, Judit; G?erri-Fern?ndez, Robert; Moya, Andr?s; Gonz?lez, Alicia; Hern?ndez, Juan J.; Lerma, Elisabet; Guelar, Ana; Sorli, Luisa; Horcajada, Juan P.; Artacho, Alejandro; D?Auria, Giuseppe; Knobel, Hernando

    2017-01-01

    Dysbalance in gut microbiota has been linked to increased microbial translocation, leading to chronic inflammation in HIV-patients, even under effective HAART. Moreover, microbial translocation is associated with insufficient reconstitution of CD4+T cells, and contributes to the pathogenesis of immunologic non-response. In a double-blind, randomised, placebo-controlled trial, we recently showed that, compared to placebo, 12 weeks treatment with probiotic Saccharomyces boulardii significantly ...

  18. Antibiotics in early life alter the gut microbiome and increase disease incidence in a spontaneous mouse model of autoimmune insulin-dependent diabetes.

    Science.gov (United States)

    Candon, Sophie; Perez-Arroyo, Alicia; Marquet, Cindy; Valette, Fabrice; Foray, Anne-Perrine; Pelletier, Benjamin; Milani, Christian; Milani, Cristian; Ventura, Marco; Bach, Jean-François; Chatenoud, Lucienne

    2015-01-01

    Insulin-dependent or type 1 diabetes is a prototypic autoimmune disease whose incidence steadily increased over the past decades in industrialized countries. Recent evidence suggests the importance of the gut microbiota to explain this trend. Here, non-obese diabetic (NOD) mice that spontaneously develop autoimmune type 1 diabetes were treated with different antibiotics to explore the influence of a targeted intestinal dysbiosis in the progression of the disease. A mixture of wide spectrum antibiotics (i.e. streptomycin, colistin and ampicillin) or vancomycin alone were administered orally from the moment of conception, treating breeding pairs, and during the postnatal and adult life until the end of follow-up at 40 weeks. Diabetes incidence significantly and similarly increased in male mice following treatment with these two antibiotic regimens. In NOD females a slight yet not significant trend towards an increase in disease incidence was observed. Changes in gut microbiota composition were assessed by sequencing the V3 region of bacterial 16S rRNA genes. Administration of the antibiotic mixture resulted in near complete ablation of the gut microbiota. Vancomycin treatment led to increased Escherichia, Lactobacillus and Sutterella genera and decreased members of the Clostridiales order and Lachnospiraceae, Prevotellaceae and Rikenellaceae families, as compared to control mice. Massive elimination of IL-17-producing cells, both CD4+TCRαβ+ and TCRγδ+ T cells was observed in the lamina propria of the ileum and the colon of vancomycin-treated mice. These results show that a directed even partial ablation of the gut microbiota, as induced by vancomycin, significantly increases type 1 diabetes incidence in male NOD mice thus prompting for caution in the use of antibiotics in pregnant women and newborns.

  19. Antibiotics in early life alter the gut microbiome and increase disease incidence in a spontaneous mouse model of autoimmune insulin-dependent diabetes.

    Directory of Open Access Journals (Sweden)

    Sophie Candon

    Full Text Available Insulin-dependent or type 1 diabetes is a prototypic autoimmune disease whose incidence steadily increased over the past decades in industrialized countries. Recent evidence suggests the importance of the gut microbiota to explain this trend. Here, non-obese diabetic (NOD mice that spontaneously develop autoimmune type 1 diabetes were treated with different antibiotics to explore the influence of a targeted intestinal dysbiosis in the progression of the disease. A mixture of wide spectrum antibiotics (i.e. streptomycin, colistin and ampicillin or vancomycin alone were administered orally from the moment of conception, treating breeding pairs, and during the postnatal and adult life until the end of follow-up at 40 weeks. Diabetes incidence significantly and similarly increased in male mice following treatment with these two antibiotic regimens. In NOD females a slight yet not significant trend towards an increase in disease incidence was observed. Changes in gut microbiota composition were assessed by sequencing the V3 region of bacterial 16S rRNA genes. Administration of the antibiotic mixture resulted in near complete ablation of the gut microbiota. Vancomycin treatment led to increased Escherichia, Lactobacillus and Sutterella genera and decreased members of the Clostridiales order and Lachnospiraceae, Prevotellaceae and Rikenellaceae families, as compared to control mice. Massive elimination of IL-17-producing cells, both CD4+TCRαβ+ and TCRγδ+ T cells was observed in the lamina propria of the ileum and the colon of vancomycin-treated mice. These results show that a directed even partial ablation of the gut microbiota, as induced by vancomycin, significantly increases type 1 diabetes incidence in male NOD mice thus prompting for caution in the use of antibiotics in pregnant women and newborns.

  20. Gut Protozoa: Friends or Foes of the Human Gut Microbiota?

    Science.gov (United States)

    Chabé, Magali; Lokmer, Ana; Ségurel, Laure

    2017-12-01

    The importance of the gut microbiota for human health has sparked a strong interest in the study of the factors that shape its composition and diversity. Despite the growing evidence suggesting that helminths and protozoa significantly interact with gut bacteria, gut microbiome studies remain mostly focused on prokaryotes and on populations living in industrialized countries that typically have a low parasite burden. We argue that protozoa, like helminths, represent an important factor to take into account when studying the gut microbiome, and that their presence - especially considering their long coevolutionary history with humans - may be beneficial. From this perspective, we examine the relationship between the protozoa and their hosts, as well as their relevance for public health. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Associations among the cecal microbiome and bacterially-derived cecal xeno-metabolites during diabetes progression in the UC Davis-Type 2 diabetes rat model

    Science.gov (United States)

    The gut microbiome is altered in obesity and diabetes, but the molecular signals linking gut microbes and host metabolic regulation have not been established. Our aim was to identify gut microbe-derived xeno-metabolites that associate with alterations in the microbiome during the progression of a t...

  2. You Are What You Eat: A Genomic Analysis of the Gut Microbiome of Captive and Wild Octopus vulgaris Paralarvae and Their Zooplankton Prey

    Directory of Open Access Journals (Sweden)

    Álvaro Roura

    2017-05-01

    Full Text Available The common octopus (Octopus vulgaris is an attractive species for aquaculture, however, several challenges inhibit sustainable commercial production. Little is known about the early paralarval stages in the wild, including diet and intestinal microbiota, which likely play a significant role in development and vitality of this important life stage. High throughput sequencing was used to characterize the gastrointestinal microbiome of wild O. vulgaris paralarvae collected from two different upwelling regions off the coast of North West Spain (n = 41 and Morocco (n = 35. These were compared to that of paralarvae reared with Artemia for up to 25 days in captivity (n = 29. In addition, the gastrointestinal microbiome of zooplankton prey (crabs, copepod and krill was also analyzed to determine if the microbial communities present in wild paralarvae are derived from their diet. Paralarvae reared in captivity with Artemia showed a depletion of bacterial diversity, particularly after day 5, when almost half the bacterial species present on day 0 were lost and two bacterial families (Mycoplasmataceae and Vibrionaceae dominated the microbial community. In contrast, bacterial diversity increased in wild paralarvae as they developed in the oceanic realm of both upwelling systems, likely due to the exposure of new bacterial communities via ingestion of a wide diversity of prey. Remarkably, the bacterial diversity of recently hatched paralarvae in captivity was similar to that of wild paralarvae and zooplankton, thus suggesting a marked effect of the diet in both the microbial community species diversity and evenness. This study provides a comprehensive overview of the bacterial communities inhabiting the gastrointestinal tract of O. vulgaris paralarvae, and reveals new research lines to challenge the current bottlenecks preventing sustainable octopus aquaculture.

  3. Microbiome/microbiota and allergies.

    Science.gov (United States)

    Inoue, Yuzaburo; Shimojo, Naoki

    2015-01-01

    Allergies are characterized by a hypersensitive immune reaction to originally harmless antigens. In recent decades, the incidence of allergic diseases has markedly increased, especially in developed countries. The increase in the frequency of allergic diseases is thought to be primarily due to environmental changes related to a westernized lifestyle, which affects the commensal microbes in the human body. The human gut is the largest organ colonized by bacteria and contains more than 1000 bacterial species, called the "gut microbiota." The recent development of sequencing technology has enabled researchers to genetically investigate and clarify the diversity of all species of commensal microbes. The collective genomes of commensal microbes are together called the "microbiome." Although the detailed mechanisms remain unclear, it has been proposed that the microbiota/microbiome, especially that in the gut, impacts the systemic immunity and metabolism, thus affecting the development of various immunological diseases, including allergies. In this review, we summarize the recent findings regarding the importance of the microbiome/microbiota in the development of allergic diseases and also the results of interventional studies using probiotics or prebiotics to prevent allergies.

  4. Healthy human gut phageome.

    Science.gov (United States)

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T; van der Oost, John; de Vos, Willem M; Young, Mark J

    2016-09-13

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20-50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health.

  5. Gut Microbiota-brain Axis

    Institute of Scientific and Technical Information of China (English)

    Hong-Xing Wang; Yu-Ping Wang

    2016-01-01

    Objective:To systematically review the updated information about the gut microbiota-brain axis.Data Sources:All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of"gut microbiota","gut-brain axis",and "neuroscience".Study Selection:All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results:It is well-recognized that gut microbiota affects the brain's physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain's neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions:Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.

  6. The microbiome of New World vultures.

    Science.gov (United States)

    Roggenbuck, Michael; Bærholm Schnell, Ida; Blom, Nikolaj; Bælum, Jacob; Bertelsen, Mads Frost; Sicheritz-Pontén, Thomas; Pontén, Thomas Sicheritz; Sørensen, Søren Johannes; Gilbert, M Thomas P; Graves, Gary R; Hansen, Lars H

    2014-11-25

    Vultures are scavengers that fill a key ecosystem niche, in which they have evolved a remarkable tolerance to bacterial toxins in decaying meat. Here we report the first deep metagenomic analysis of the vulture microbiome. Through face and gut comparisons of 50 vultures representing two species, we demonstrate a remarkably conserved low diversity of gut microbial flora. The gut samples contained an average of 76 operational taxonomic units (OTUs) per specimen, compared with 528 OTUs on the facial skin. Clostridia and Fusobacteria, widely pathogenic to other vertebrates, dominate the vulture's gut microbiota. We reveal a likely faecal-oral-gut route for their origin. DNA of prey species detectable on facial swabs was completely degraded in the gut samples from most vultures, suggesting that the gastrointestinal tracts of vultures are extremely selective. Our findings show a strong adaption of vultures and their bacteria to their food source, exemplifying a specialized host-microbial alliance.

  7. The microbiome of New World vultures

    DEFF Research Database (Denmark)

    Roggenbuck, Michael; Schnell, Ida Baerholm; Blom, Nikolaj

    2014-01-01

    Vultures are scavengers that fill a key ecosystem niche, in which they have evolved a remarkable tolerance to bacterial toxins in decaying meat. Here we report the first deep metagenomic analysis of the vulture microbiome. Through face and gut comparisons of 50 vultures representing two species, we...... demonstrate a remarkably conserved low diversity of gut microbial flora. The gut samples contained an average of 76 operational taxonomic units (OTUs) per specimen, compared with 528 OTUs on the facial skin. Clostridia and Fusobacteria, widely pathogenic to other vertebrates, dominate the vulture's gut...... microbiota. We reveal a likely faecal-oral-gut route for their origin. DNA of prey species detectable on facial swabs was completely degraded in the gut samples from most vultures, suggesting that the gastrointestinal tracts of vultures are extremely selective. Our findings show a strong adaption of vultures...

  8. Transglycosylated Starch Modulates the Gut Microbiome and Expression of Genes Related to Lipid Synthesis in Liver and Adipose Tissue of Pigs

    Directory of Open Access Journals (Sweden)

    Monica A. Newman

    2018-02-01

    Full Text Available Dietary inclusion of resistant starches can promote host health through modulation of the gastrointestinal microbiota, short-chain fatty acid (SCFA profiles, and lipid metabolism. This study investigated the impact of a transglycosylated cornstarch (TGS on gastric, ileal, cecal, proximal-colonic, and mid-colonic bacterial community profiles and fermentation metabolites using a growing pig model. It additionally evaluated the effect of TGS on the expression of host genes related to glucose and SCFA absorption, incretins, and satiety in the gut as well as host genes related to lipid metabolism in hepatic and adipose tissue. Sixteen growing pigs (4 months of age were fed either a TGS or control (CON diet for 11 days. Bacterial profiles were determined via Illumina MiSeq sequencing of the V3–5 region of the 16S rRNA gene, whereas SCFA and gene expression were measured using gas chromatography and reverse transcription-quantitative PCR. Megasphaera, which was increased at all gut sites, began to benefit from TGS feeding in gastric digesta, likely through cross-feeding with other microbes, such as Lactobacillus. Shifts in the bacterial profiles from dietary TGS consumption in the cecum, proximal colon, and mid colon were similar. Relative abundances of Ruminococcus and unclassified Ruminococcaceae genus were lower, whereas that of unclassified Veillonellaceae genus was higher in TGS- compared to CON-fed pigs (p < 0.05. TGS consumption also increased (p < 0.05 concentrations of SCFA, especially propionate, and lactate in the distal hindgut compared to the CON diet which might have up-regulated GLP1 expression in the cecum (p < 0.05 and mid colon compared to the control diet (p < 0.10. TGS-fed pigs showed increased hepatic and decreased adipocyte expression of genes for lipid synthesis (FASN, SREBP1, and ACACA compared to CON-fed pigs, which may be related to postprandial portal nutrient flow and reduced systemic insulin signaling. Overall, our data

  9. A randomised, controlled, crossover study of the effect of diet on angiopoietin-like protein 4 (ANGPTL4) through modification of the gut microbiome

    DEFF Research Database (Denmark)

    Blædel, Trine; Holm, Jacob B.; Sundekilde, Ulrik Kræmer

    2016-01-01

    -fat milk or as a result of fermentation of inulin. This study investigated whether a standardised diet either high in fat content or supplemented with inulin powder would increase plasma ANGPTL4 in overweight men and whether this increase was mediated through a compositional change of the gut microbiota....... The study had a crossover design with three arms, where participants were given a standardised isoenergetic diet supplemented with inulin powder, whole-fat milk or water (control). Plasma and urine samples were collected before and after each intervention period. Faecal samples and adipose tissue biopsies...... of bifidobacteria following the inulin diet was higher, compared with the control diet. However, the changes in microbiota were not associated with plasma ANGPTL4 and the overall composition of the microbiota did not change between the dietary periods. Although weight was maintained throughout the dietary periods...

  10. Two randomized cross-over trials assessing the impact of dietary gluten or wholegrain on the gut microbiome and host metabolic health

    DEFF Research Database (Denmark)

    Ibrügger, Sabine; Gøbel, Rikke Juul; Vestergaard, Henrik

    2014-01-01

    as baseline characteristics of two human intervention studies, within the Gut, Grain and Greens (3G) Center, investigating the effects of a gluten-poor and wholegrain-rich diet on microbiota composition and metabolic health. Design: The gluten and wholegrain studies had a randomized, controlled, cross......-over design each comprising two eight-week dietary intervention periods, separated by a six-week wash-out period. Each trial included 60 men and women exhibiting an increased metabolic risk. In the gluten study a gluten-poor diet was compared with a gluten-rich dietary fiber-controlled diet......, and in the wholegrain study a wholegrain-rich diet was compared with a refined grain diet. The control diet was identical in both studies, being concomitantly high in gluten and refined. Participants substituted all cereal products with provided intervention products which they consumed ad libitum. Before and after...

  11. Increased butyrate priming in the gut stalls microbiome associated-gastrointestinal inflammation and hepatic metabolic reprogramming in a mouse model of Gulf War Illness.

    Science.gov (United States)

    Seth, Ratanesh Kumar; Kimono, Diana; Alhasson, Firas; Sarkar, Sutapa; Albadrani, Muayad; Lasley, Stephen K; Horner, Ronnie; Janulewicz, Patricia; Nagarkatti, Mitzi; Nagarkatti, Prakash; Sullivan, Kimberly; Chatterjee, Saurabh

    2018-07-01

    Most of the associated pathologies in Gulf War Illness (GWI) have been ascribed to chemical and pharmaceutical exposures during the war. Since an increased number of veterans complain of gastrointestinal (GI), neuroinflammatory and metabolic complications as they age and there are limited options for a cure, the present study was focused to assess the role of butyrate, a short chain fatty acid for attenuating GWI-associated GI and metabolic complications. Results in a GWI-mouse model of permethrin and pyridostigmine bromide (PB) exposure showed that oral butyrate restored gut homeostasis and increased GPR109A receptor copies in the small intestine (SI). Claudin-2, a protein shown to be upregulated in conditions of leaky gut was significantly decreased following butyrate administration. Butyrate decreased TLR4 and TLR5 expressions in the liver concomitant to a decrease in TLR4 activation. GW-chemical exposure showed no clinical signs of liver disease but a significant alteration of metabolic markers such as SREBP1c, PPAR-α, and PFK was evident. Liver markers for lipogenesis and carbohydrate metabolism that were significantly upregulated following GW chemical exposure were attenuated by butyrate priming in vivo and in human primary hepatocytes. Further, Glucose transporter Glut-4 that was shown to be elevated following liver complications were significantly decreased in these mice after butyrate administration. Finally, use of TLR4 KO mice completely attenuated the liver metabolic changes suggesting the central role of these receptors in the GWI pathology. In conclusion, we report a butyrate specific mechanistic approach to identify and treat increased metabolic abnormalities in GWI veterans with systemic inflammation, chronic fatigue, GI disturbances, metabolic complications and weight gain. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Embracing community ecology in plant microbiome research

    NARCIS (Netherlands)

    Dini-Andreote, F.; Raaijmakers, J.M.

    2018-01-01

    Community assembly is mediated by selection, dispersal, drift, and speciation. Environmental selection is mostly used to date to explain patterns in plant microbiome assembly, whereas the influence of the other processes remains largely elusive. Recent studies highlight that adopting community

  13. A snapshot of gut microbiota of an adult urban population from Western region of India.

    Science.gov (United States)

    Tandon, Disha; Haque, Mohammed Monzoorul; R, Saravanan; Shaikh, Shafiq; P, Sriram; Dubey, Ashok Kumar; Mande, Sharmila S

    2018-01-01

    The human gut microbiome contributes to a broad range of biochemical and metabolic functions that directly or indirectly affect human physiology. Several recent studies have indicated that factors like age, geographical location, genetic makeup, and individual health status significantly influence the diversity, stability, and resilience of the gut microbiome. Of the mentioned factors, geographical location (and related dietary/socio-economic context) appears to explain a significant portion of microbiome variation observed in various previously conducted base-line studies on human gut microbiome. Given this context, we have undertaken a microbiome study with the objective of cataloguing the taxonomic diversity of gut microbiomes sampled from an urban cohort from Ahmedabad city in Western India. Computational analysis of microbiome sequence data corresponding to 160 stool samples (collected from 80 healthy individuals at two time-points, 60 days apart) has indicated a Prevotella-dominated microbial community. Given that the typical diet of participants included carbohydrate and fibre-rich components (predominantly whole grains and legume-based preparations), results appear to validate the proposed correlation between diet/geography and microbiome composition. Comparative analysis of obtained gut microbiome profiles with previously published microbiome profiles from US, China, Finland, and Japan additionally reveals a distinct taxonomic and (inferred) functional niche for the sampled microbiomes.

  14. Metformin Alters Gut Microbiota of Healthy Mice: Implication for Its Potential Role in Gut Microbiota Homeostasis

    Directory of Open Access Journals (Sweden)

    Wei Ma

    2018-06-01

    Full Text Available In recent years, the first-line anti-diabetic drug metformin has been shown to be also useful for the treatment of other diseases like cancer. To date, few reports were about the impact of metformin on gut microbiota. To fully understand the mechanism of action of metformin in treating diseases other than diabetes, it is especially important to investigate the impact of long-term metformin treatment on the gut microbiome in non-diabetic status. In this study, we treated healthy mice with metformin for 30 days, and observed 46 significantly changed gut microbes by using the 16S rRNA-based microbiome profiling technique. We found that microbes from the Verrucomicrobiaceae and Prevotellaceae classes were enriched, while those from Lachnospiraceae and Rhodobacteraceae were depleted. We further compared the altered microbiome profile with the profiles under various disease conditions using our recently developed comparative microbiome tool known as MicroPattern. Interestingly, the treatment of diabetes patients with metformin positively correlates with colon cancer and type 1 diabetes, indicating a confounding effect on the gut microbiome in patients with diabetes. However, the treatment of healthy mice with metformin exhibits a negative correlation with multiple inflammatory diseases, indicating a protective anti-inflammatory role of metformin in non-diabetes status. This result underscores the potential effect of metformin on gut microbiome homeostasis, which may contribute to the treatment of non-diabetic diseases.

  15. An in vitro model of the horse gut microbiome enables identification of lactate-utilizing bacteria that differentially respond to starch induction.

    Science.gov (United States)

    Biddle, Amy S; Black, Samuel J; Blanchard, Jeffrey L

    2013-01-01

    Laminitis is a chronic, crippling disease triggered by the sudden influx of dietary starch. Starch reaches the hindgut resulting in enrichment of lactic acid bacteria, lactate accumulation, and acidification of the gut contents. Bacterial products enter the bloodstream and precipitate systemic inflammation. Hindgut lactate levels are normally low because specific bacterial groups convert lactate to short chain fatty acids. Why this mechanism fails when lactate levels rapidly rise, and why some hindgut communities can recover is unknown. Fecal samples from three adult horses eating identical diets provided bacterial communities for this in vitro study. Triplicate microcosms of fecal slurries were enriched with lactate and/or starch. Metabolic products (short chain fatty acids, headspace gases, and hydrogen sulfide) were measured and microbial community compositions determined using Illumina 16S rRNA sequencing over 12-hour intervals. We report that patterns of change in short chain fatty acid levels and pH in our in vitro system are similar to those seen in in vivo laminitis induction models. Community differences between microcosms with disparate abilities to clear excess lactate suggest profiles conferring resistance of starch-induction conditions. Where lactate levels recover following starch induction conditions, propionate and acetate levels rise correspondingly and taxa related to Megasphaeraelsdenii reach levels exceeding 70% relative abundance. In lactate and control cultures, taxa related to Veillonellamontpellierensis are enriched as lactate levels fall. Understanding these community differences and factors promoting the growth of specific lactate utilizing taxa may be useful to prevent acidosis under starch-induction conditions.

  16. Glyphosate’s Suppression of Cytochrome P450 Enzymes and Amino Acid Biosynthesis by the Gut Microbiome: Pathways to Modern Diseases

    Directory of Open Access Journals (Sweden)

    Anthony Samsel

    2013-04-01

    Full Text Available Glyphosate, the active ingredient in Roundup®, is the most popular herbicide used worldwide. The industry asserts it is minimally toxic to humans, but here we argue otherwise. Residues are found in the main foods of the Western diet, comprised primarily of sugar, corn, soy and wheat. Glyphosate's inhibition of cytochrome P450 (CYP enzymes is an overlooked component of its toxicity to mammals. CYP enzymes play crucial roles in biology, one of which is to detoxify xenobiotics. Thus, glyphosate enhances the damaging effects of other food borne chemical residues and environmental toxins. Negative impact on the body is insidious and manifests slowly over time as inflammation damages cellular systems throughout the body. Here, we show how interference with CYP enzymes acts synergistically with disruption of the biosynthesis of aromatic amino acids by gut bacteria, as well as impairment in serum sulfate transport. Consequences are most of the diseases and conditions associated with a Western diet, which include gastrointestinal disorders, obesity, diabetes, heart disease, depression, autism, infertility, cancer and Alzheimer’s disease. We explain the documented effects of glyphosate and its ability to induce disease, and we show that glyphosate is the “textbook example” of exogenous semiotic entropy: the disruption of homeostasis by environmental toxins.

  17. The metabolic role of the gut microbiota in health and rheumatic disease: mechanisms and interventions

    NARCIS (Netherlands)

    Abdollahi-Roodsaz, S.; Abramson, S.B.; Scher, J.U.

    2016-01-01

    The role of the gut microbiome in animal models of inflammatory and autoimmune disease is now well established. The human gut microbiome is currently being studied as a potential modulator of the immune response in rheumatic disorders. However, the vastness and complexity of this host-microorganism

  18. Diets high in resistant starch increase plasma levels of trimethylamine-N-oxide, a gut microbiome metabolite associated with CVD risk

    Energy Technology Data Exchange (ETDEWEB)

    Bergeron, Nathalie; Williams, Paul T.; Lamendella, Regina; Faghihnia, Nastaran; Grube, Alyssa; Li, Xinmin; Wang, Zeneng; Knight, Rob; Jansson, Janet K.; Hazen, Stanley L.; Krauss, Ronald M.

    2016-12-20

    Production of trimethylamine-N-oxide (TMAO), a biomarker of CVD risk, is dependent on intestinal microbiota, but little is known of dietary conditions promoting changes in gut microbial communities. Resistant starches (RS) alter the human microbiota. We sought to determine whether diets varying in RS and carbohydrate (CHO) content affect plasma TMAO levels. We also assessed postprandial glucose and insulin responses and plasma lipid changes to diets high and low in RS. In a cross-over trial, fifty-two men and women consumed a 2-week baseline diet (41 percentage of energy (%E) CHO, 40 % fat, 19 % protein), followed by 2-week high- and low-RS diets separated by 2-week washouts. RS diets were assigned at random within the context of higher (51–53 %E)v. lower CHO (39–40 %E) intake. Measurements were obtained in the fasting state and, for glucose and insulin, during a meal test matching the composition of the assigned diet. With lower CHO intake, plasma TMAO, carnitine, betaine andγ-butyrobetaine concentrations were higher after the high-v. low-RS diet (P<0·01 each). These metabolites were not differentially affected by highv. low RS when CHO intake was high. Although the high-RS meal reduced postprandial insulin and glucose responses when CHO intake was low (P<0·01 each), RS did not affect fasting lipids, lipoproteins, glucose or insulin irrespective of dietary CHO content. In conclusion, a lower-CHO diet high in RS was associated with higher plasma TMAO levels. These findings, together with the absence of change in fasting lipids, suggest that short-term high-RS diets do not improve markers of cardiometabolic health.

  19. An in vitro model of the horse gut microbiome enables identification of lactate-utilizing bacteria that differentially respond to starch induction.

    Directory of Open Access Journals (Sweden)

    Amy S Biddle

    Full Text Available Laminitis is a chronic, crippling disease triggered by the sudden influx of dietary starch. Starch reaches the hindgut resulting in enrichment of lactic acid bacteria, lactate accumulation, and acidification of the gut contents. Bacterial products enter the bloodstream and precipitate systemic inflammation. Hindgut lactate levels are normally low because specific bacterial groups convert lactate to short chain fatty acids. Why this mechanism fails when lactate levels rapidly rise, and why some hindgut communities can recover is unknown. Fecal samples from three adult horses eating identical diets provided bacterial communities for this in vitro study. Triplicate microcosms of fecal slurries were enriched with lactate and/or starch. Metabolic products (short chain fatty acids, headspace gases, and hydrogen sulfide were measured and microbial community compositions determined using Illumina 16S rRNA sequencing over 12-hour intervals. We report that patterns of change in short chain fatty acid levels and pH in our in vitro system are similar to those seen in in vivo laminitis induction models. Community differences between microcosms with disparate abilities to clear excess lactate suggest profiles conferring resistance of starch-induction conditions. Where lactate levels recover following starch induction conditions, propionate and acetate levels rise correspondingly and taxa related to Megasphaeraelsdenii reach levels exceeding 70% relative abundance. In lactate and control cultures, taxa related to Veillonellamontpellierensis are enriched as lactate levels fall. Understanding these community differences and factors promoting the growth of specific lactate utilizing taxa may be useful to prevent acidosis under starch-induction conditions.

  20. Gut-Bioreactor and Human Health in Future.

    Science.gov (United States)

    Purohit, Hemant J

    2018-03-01

    Gut-microbiome provides the complementary metabolic potential to the human system. To understand the active participation and the performance of the microbial community in human health, the concept of gut as a plug-flow reactor with the fed-batch mode of operation can provide better insight. The concept suggests the virtual compartmentalized gut with sequential stratification of the microbial community in response to a typical host genotype. It also provides the analysis plan for gut microbiome; and its relevance in developing health management options under the identified clinical conditions.

  1. The microbiome and HIV persistence: implications for viral remission and cure.

    Science.gov (United States)

    Koay, Wei Li A; Siems, Lilly V; Persaud, Deborah

    2018-01-01

    This article discusses the interaction between HIV infection, the gut microbiome, inflammation and immune activation, and HIV reservoirs, along with interventions to target the microbiome and their implications for HIV remission and cure. Most studies show that HIV-infected adults have a gut microbiome associated with decreased bacterial richness and diversity, and associated systemic inflammation and immune activation. A unique set of individuals, elite controllers, who spontaneously control HIV replication, have a similar microbiome to HIV-uninfected individuals. Conversely, exposure to maternal HIV in infants was shown to alter the gut microbiome, even in infants who escaped perinatal infection. Emerging research highlights the importance of the metabolomics and metaproteomics of the gut microbiome, which may have relevance for HIV remission and cure. Together, these studies illustrate the complexity of the relationship between HIV infection, the gut microbiome, and its systemic effects. Understanding the association of HIV with the microbiome, metabolome, and metaproteome may lead to novel therapies to decrease inflammation and immune activation, and impact HIV reservoir size and vaccine responses. Further research in this area is important to inform HIV remission and cure treatments.

  2. Feeding on microbiomes: effects of detritivory on the taxonomic and phylogenetic bacterial composition of animal manures.

    Science.gov (United States)

    Aira, Manuel; Bybee, Seth; Pérez-Losada, Marcos; Domínguez, Jorge

    2015-11-01

    Earthworms play a key role in nutrient cycling by interacting with microorganisms thus accelerating organic matter turnover in soil systems. As detritivores, some earthworm types ingest and digest a mixture of dead organic matter and microorganisms, like animal manures (i.e. animal gut microbiomes). Here we described the earthworm cast microbiome and the role ingested bacteria play on its composition. We fed Eisenia andrei with cow, horse and pig manures and determined the taxonomic and phylogenetic composition of the these manures before and after passage through the earthworm gut. Earthworm cast microbiomes showed a smaller diversity than the manure they fed on. Manures strongly differed in their taxonomic and phylogenetic composition, but these differences were markedly reduced once transformed into earthworm cast microbiomes after passage through the earthworm gut. The core earthworm cast microbiome comprised 30 OTUs (2.6% of OTUs from cast samples), of which 10 are possibly native to the earthworm gut. Most of the core cast microbiome OTUs belonged to phyla Actinobacteria and Proteobacteria, as opposed to already described animal core gut microbiomes, which are composed mainly of Firmicutes and Bacteroidetes. Our results suggest that earthworms build up their cast microbiome by selecting from the pool of ingested bacteria. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  3. Proton pump inhibitors alter the composition of the gut microbiota.

    Science.gov (United States)

    Jackson, Matthew A; Goodrich, Julia K; Maxan, Maria-Emanuela; Freedberg, Daniel E; Abrams, Julian A; Poole, Angela C; Sutter, Jessica L; Welter, Daphne; Ley, Ruth E; Bell, Jordana T; Spector, Tim D; Steves, Claire J

    2016-05-01

    Proton pump inhibitors (PPIs) are drugs used to suppress gastric acid production and treat GI disorders such as peptic ulcers and gastro-oesophageal reflux. They have been considered low risk, have been widely adopted, and are often over-prescribed. Recent studies have identified an increased risk of enteric and other infections with their use. Small studies have identified possible associations between PPI use and GI microbiota, but this has yet to be carried out on a large population-based cohort. We investigated the association between PPI usage and the gut microbiome using 16S ribosomal RNA amplification from faecal samples of 1827 healthy twins, replicating results within unpublished data from an interventional study. We identified a significantly lower abundance in gut commensals and lower microbial diversity in PPI users, with an associated significant increase in the abundance of oral and upper GI tract commensals. In particular, significant increases were observed in Streptococcaceae. These associations were replicated in an independent interventional study and in a paired analysis between 70 monozygotic twin pairs who were discordant for PPI use. We propose that the observed changes result from the removal of the low pH barrier between upper GI tract bacteria and the lower gut. Our findings describe a significant impact of PPIs on the gut microbiome and should caution over-use of PPIs, and warrant further investigation into the mechanisms and their clinical consequences. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  4. Childhood malnutrition and the intestinal microbiome.

    Science.gov (United States)

    Kane, Anne V; Dinh, Duy M; Ward, Honorine D

    2015-01-01

    Malnutrition contributes to almost half of all deaths in children under the age of 5 y, particularly those who live in resource-constrained areas. Those who survive frequently suffer from long-term sequelae including growth failure and neurodevelopmental impairment. Malnutrition is part of a vicious cycle of impaired immunity, recurrent infections, and worsening malnutrition. Recently, alterations in the gut microbiome have also been strongly implicated in childhood malnutrition. It has been suggested that malnutrition may delay the normal development of the gut microbiota in early childhood or force it toward an altered composition that lacks the required functions for healthy growth and/or increases the risk for intestinal inflammation. This review addresses our current understanding of the beneficial contributions of gut microbiota to human nutrition (and conversely the potential role of changes in that community to malnutrition), the process of acquiring an intestinal microbiome, potential influences of malnutrition on the developing microbiota, and the evidence directly linking alterations in the intestinal microbiome to childhood malnutrition. We review recent studies on the association between alterations in the intestinal microbiome and early childhood malnutrition and discuss them in the context of implications for intervention or prevention of the devastation caused by malnutrition.

  5. Emulating Host-Microbiome Ecosystem of Human Gastrointestinal Tract in Vitro.

    Science.gov (United States)

    Park, Gun-Seok; Park, Min Hee; Shin, Woojung; Zhao, Connie; Sheikh, Sameer; Oh, So Jung; Kim, Hyun Jung

    2017-06-01

    The human gut microbiome performs prodigious physiological functions such as production of microbial metabolites, modulation of nutrient digestion and drug metabolism, control of immune system, and prevention of infection. Paradoxically, gut microbiome can also negatively orchestrate the host responses in diseases or chronic disorders, suggesting that the regulated and balanced host-gut microbiome crosstalk is a salient prerequisite in gastrointestinal physiology. To understand the pathophysiological role of host-microbiome crosstalk, it is critical to recreate in vivo relevant models of the host-gut microbiome ecosystem in human. However, controlling the multi-species microbial communities and their uncontrolled growth has remained a notable technical challenge. Furthermore, conventional two-dimensional (2D) or 3D culture systems do not recapitulate multicellular microarchitectures, mechanical dynamics, and tissue-specific functions. Here, we review recent advances and current pitfalls of in vitro and ex vivo models that display human GI functions. We also discuss how the disruptive technologies such as 3D organoids or a human organ-on-a-chip microphysiological system can contribute to better emulate host-gut microbiome crosstalks in health and disease. Finally, the medical and pharmaceutical significance of the gut microbiome-based personalized interventions is underlined as a future perspective.

  6. The gut microbiota in type 2 diabetes

    DEFF Research Database (Denmark)

    Nielsen, Trine; Allin, Kristine Højgaard; Pedersen, Oluf

    2016-01-01

    The exploration of the gut microbiota has intensified within the past decade with the introduction of cultivation-independent methods. By investigation of the gut bacterial genes, our understanding of the compositional and functional capability of the gut microbiome has increased. It is now widely...... recognized that the gut microbiota has profound effect on host metabolism and recently changes in the gut microbiota have been associated with type 2 diabetes. Animal models and human studies have linked changes in the gut microbiota to the induction of low-grade inflammation, altered immune response......, and changes in lipid and glucose metabolism. Several factors have been identified that might affect the healthy microbiota, potentially inducing a dysbiotic microbiota associated with a disease state. This increased understanding of the gut microbiota might potentially contribute to targeted intervention...

  7. Breast tissue, oral and urinary microbiomes in breast cancer

    OpenAIRE

    Wang, Hannah; Altemus, Jessica; Niazi, Farshad; Green, Holly; Calhoun, Benjamin C.; Sturgis, Charles; Grobmyer, Stephen R.; Eng, Charis

    2017-01-01

    It has long been proposed that the gut microbiome contributes to breast carcinogenesis by modifying systemic estrogen levels. This is often cited as a possible mechanism linking breast cancer and high-fat, low-fiber diets as well as antibiotic exposure, associations previously identified in population-based studies. More recently, a distinct microbiome has been identified within breast milk and tissue, but few studies have characterized differences in the breast tissue microbiota of patients ...

  8. Enzyme-treated wheat bran alters gut microbiota and liver metabolome in mice fed a high fat diet

    Science.gov (United States)

    Enzyme-treated wheat bran (ETWB) is a fermentable dietary fiber that has been shown to decrease body fat and modify the gut microbiome. However, it is not clear how these microbiome changes impact peripheral tissue metabolism. We hypothesized that supplementation with ETWB would change gut-derived...

  9. Microbiome, Metabolome and Inflammatory Bowel Disease

    Directory of Open Access Journals (Sweden)

    Ishfaq Ahmed

    2016-06-01

    Full Text Available Inflammatory Bowel Disease (IBD is a multifactorial disorder that conceptually occurs as a result of altered immune responses to commensal and/or pathogenic gut microbes in individuals most susceptible to the disease. During Crohn’s Disease (CD or Ulcerative Colitis (UC, two components of the human IBD, distinct stages define the disease onset, severity, progression and remission. Epigenetic, environmental (microbiome, metabolome and nutritional factors are important in IBD pathogenesis. While the dysbiotic microbiota has been proposed to play a role in disease pathogenesis, the data on IBD and diet are still less convincing. Nonetheless, studies are ongoing to examine the effect of pre/probiotics and/or FODMAP reduced diets on both the gut microbiome and its metabolome in an effort to define the healthy diet in patients with IBD. Knowledge of a unique metabolomic fingerprint in IBD could be useful for diagnosis, treatment and detection of disease pathogenesis.

  10. Factors Affecting Gastrointestinal Microbiome Development in Neonates

    Directory of Open Access Journals (Sweden)

    Clara Yieh Lin Chong

    2018-02-01

    Full Text Available The gut microbiome is established in the newborn period and is recognised to interact with the host to influence metabolism. Different environmental factors that are encountered during this critical period may influence the gut microbial composition, potentially impacting upon later disease risk, such as asthma, metabolic disorder, and inflammatory bowel disease. The sterility dogma of the foetus in utero is challenged by studies that identified bacteria, bacterial DNA, or bacterial products in meconium, amniotic fluid, and the placenta; indicating the initiation of maternal-to-offspring microbial colonisation in utero. This narrative review aims to provide a better understanding of factors that affect the development of the gastrointestinal (GI microbiome during prenatal, perinatal to postnatal life, and their reciprocal relationship with GI tract development in neonates.

  11. UNRAVELING THE FUNCTIONS OF THE MACROALGAL MICROBIOME

    Directory of Open Access Journals (Sweden)

    Ravindra Pal Singh

    2016-01-01

    Full Text Available Macroalgae are a diverse group of photosynthetic eukaryotic lower organisms and offer indispensable ecosystem services towards sustainable productivity of rocky coastal areas. The earlier studies have mainly focused on elucidation of the roles of the epiphytic bacterial communities in the ecophysiology of the host macroalga. However, mutualistic interactions have become topic of current interest. It is evident from recent studies that a fraction of epiphytic bacterial communities can be categorized as core microbial species, suggesting an obligate association. Epiphytic bacterial communities have also been reported to protect macroalgal surfaces from biofouling microorganisms through production of biologically active metabolites. Because of their intrinsic roles in the host life cycle, the host in turn may provide necessary organic nutrients in order to woo pelagic microbial communities to settle on the host surfaces. However, the precise composition of microbiomes and their functional partnership with hosts are hardly understood. In contrast, the microbial studies associated with human skin and gut and plants have significantly advanced our knowledge on microbiome and their functional interactions with the host. This has led to manipulation of the microbial flora of the human gut and of agricultural plants for improving health and performance. Therefore, it is highly imperative to investigate the functional microbiome that is closely involved in the life cycles of the host macroalgae using high-throughput techniques (metagenomics and metatranscriptomics. The findings from such investigations would help in promoting health and productivity in macroalgal species through regulation of functionally active microbiome.

  12. Metagenomics Study on the Polymorphism of Gut Microbiota and Their Function on Human Health

    DEFF Research Database (Denmark)

    Feng, Qiang

    diversity and functional complexity of the gut microbiome. Facilitated by the Next Generation Sequencing (NGS) technologies and the progress of bioinformatics in the past decade, we have acquired substantial achievements in metagenomic studies on human gut microbiome and established the fundamentals of our...... understanding of the interactions between gut microbes and human body, and also the importance of this interaction on human health. As one of the milestones, the first integrated gene catalog in the human gut microbiome was constructed in 2010 in the scheme of the Metagenomics of Human Intestinal Tract (Meta......’ are shared in the population. These microorganisms participate in various metabolic pathways and activities of the immune system and the nervous system of our bodies,and have fundamental impacts on our health. For example, an association study between gut microbiome and type 2 diabetes (T2D) highlighted...

  13. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota

    DEFF Research Database (Denmark)

    Forslund, Kristoffer; Hildebrand, Falk ; Nielsen, Trine N.

    2015-01-01

    In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported1,2. In most of these reports, treatment regimens were not controlled for and conclusions could thus be confounded by the effects of various drugs...... on the microbiota, which may obscure microbial causes, protective factors or diagnostically relevant signals. Our study addresses disease and drug signatures in the human gut microbiome of type 2 diabetes mellitus (T2D). Two previous quantitative gut metagenomics studies of T2D patients that were unstratified......, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa3,4. These in turn cause functional microbiome shifts, in part alleviated by metformin-induced changes. Overall, the present study emphasizes the need to disentangle gut microbiota signatures...

  14. Bioactive polysaccharides and gut microbiome (abstract)

    Science.gov (United States)

    Many polysaccharides have shown the ability to reduce plasma cholesterol or postprandial glycemia. Viscosity in the small intestine seems to be required to slow glucose uptake. Cereal mixed linkage beta-glucans, psyllium, glucomannans, and other polysaccharides also seem to require higher molecula...

  15. Gut-Brain Axis and Behavior.

    Science.gov (United States)

    Martin, Clair R; Mayer, Emeran A

    2017-01-01

    In the last 5 years, interest in the interactions among the gut microbiome, brain, and behavior has exploded. Preclinical evidence supports a role of the gut microbiome in behavioral responses associated with pain, emotion, social interactions, and food intake. Limited, but growing, clinical evidence comes primarily from associations of gut microbial composition and function to behavioral and clinical features and brain structure and function. Converging evidence suggests that the brain and the gut microbiota are in bidirectional communication. Observed dysbiotic states in depression, chronic stress, and autism may reflect altered brain signaling to the gut, while altered gut microbial signaling to the brain may play a role in reinforcing brain alterations. On the other hand, primary dysbiotic states due to Western diets may signal to the brain, altering ingestive behavior. While studies performed in patients with depression and rodent models generated by fecal microbial transfer from such patients suggest causation, evidence for an influence of acute gut microbial alterations on human behavioral and clinical parameters is lacking. Only recently has an open-label microbial transfer therapy in children with autism tentatively validated the gut microbiota as a therapeutic target. The translational potential of preclinical findings remains unclear without further clinical investigation. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

  16. Behind every great ant, there is a great gut

    DEFF Research Database (Denmark)

    Poulsen, Michael; Sapountzis, Panagiotis

    2012-01-01

    on the potential contribution of the ants’ gut symbionts. This issue of Molecular Ecology contains a study by Anderson et al. (2012), who take a comparative approach to explore the link between trophic levels and ant microbiomes, specifically, to address three main questions: (i) Do closely related herbivorous...... conserved gut microbiomes, suggesting symbiont functions that directly relate to dietary preference of the ant host. These findings suggest an ecological role of gut symbionts in ants, for example, in metabolism and/or protection, and the comparative approach taken supports a model of co-evolut