Enterochromaffin cells of the human gut: sensors for spices and odorants.

Science.gov (United States)

Braun, Thomas; Voland, Petra; Kunz, Lars; Prinz, Christian; Gratzl, Manfred

2007-05-01

Release of serotonin from mucosal enterochromaffin cells triggered by luminal substances is the key event in the regulation of gut motility and secretion. We were interested to know whether nasal olfactory receptors are also expressed in the human gut mucosa by enterochromaffin cells and whether their ligands and odorants present in spices, fragrances, detergents, and cosmetics cause serotonin release. Receptor expression was studied by the reverse-transcription polymerase chain reaction method in human mucosal enterochromaffin cells isolated by laser microdissection and in a cell line derived from human enterochromaffin cells. Activation of the cells by odorants was investigated by digital fluorescence imaging using the fluorescent Ca(2+) indicator Fluo-4. Serotonin release was measured in culture supernatants by a serotonin enzyme immunoassay and amperometry using carbon fiber microelectrodes placed on single cells. We found expression of 4 olfactory receptors in microdissected human mucosal enterochromaffin cells and in a cell line derived from human enterochromaffin cells. Ca(2+) imaging studies revealed that odorant ligands of the identified olfactory receptors cause Ca(2+) influx, elevation of intracellular free Ca(2+) levels, and, consequently, serotonin release. Our results show that odorants present in the luminal environment of the gut may stimulate serotonin release via olfactory receptors present in human enterochromaffin cells. Serotonin controls both gut motility and secretion and is implicated in pathologic conditions such as vomiting, diarrhea, and irritable bowel syndrome. Thus, olfactory receptors are potential novel targets for the treatment of gastrointestinal diseases and motility disorders.

The gut microbiota, environment and diseases of modern society.

Science.gov (United States)

Kelsen, Judith R; Wu, Gary D

2012-01-01

The human gut microbiota is a complex community that provides important metabolic functions to the host. Consequently, alterations in the gut microbiota have been associated with the pathogenesis of several human diseases associated with a disturbance in metabolism, particularly those that have been increasing in incidence over the last several decades including obesity, diabetes and atherosclerosis. In this review, we explore how advances in deep DNA sequencing technology have provided us a greater understanding of the factors that influence that composition of the gut microbiota and its possible links to the pathogenesis of these diseases.

Impact of human milk bacteria and oligosaccharides on neonatal gut microbiota establishment and gut health.

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Jost, Ted; Lacroix, Christophe; Braegger, Christian; Chassard, Christophe

2015-07-01

Neonatal gut microbiota establishment represents a crucial stage for gut maturation, metabolic and immunologic programming, and consequently short- and long-term health status. Human milk beneficially influences this process due to its dynamic profile of age-adapted nutrients and bioactive components and by providing commensal maternal bacteria to the neonatal gut. These include Lactobacillus spp., as well as obligate anaerobes such as Bifidobacterium spp., which may originate from the maternal gut via an enteromammary pathway as a novel form of mother-neonate communication. Additionally, human milk harbors a broad range of oligosaccharides that promote the growth and activity of specific bacterial populations, in particular, Bifidobacterium and Bacteroides spp. This review focuses on the diversity and origin of human milk bacteria, as well as on milk oligosaccharides that influence neonatal gut microbiota establishment. This knowledge can be used to develop infant formulae that more closely mimic nature's model and sustain a healthy gut microbiota. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hh pathway expression in human gut tissues and in inflammatory gut diseases

NARCIS (Netherlands)

Nielsen, Corinne M.; Williams, Jerrell; van den Brink, Gijs R.; Lauwers, Gregory Y.; Roberts, Drucilla J.

2004-01-01

Sonic hedgehog (Shh) directs early gut patterning via epithelial-mesenchymal signaling and remains expressed in endoderm-derived tissues into the adult period. In human adult gut epithelium SHH/SHH expression is strongest in basal layers, which suggests that SHH may function in the maintenance of

The first microbial colonizers of the human gut

NARCIS (Netherlands)

Milani, Christian; Duranti, Sabrina; Bottacini, Francesca; Casey, Eoghan; Turroni, Francesca; Mahony, Jennifer; Belzer, Clara; Palacio, Susana Delgado; Montes, Silvia Arboleya; Mancabelli, Leonardo; Lugli, Gabriele Andrea; Rodriguez, Juan Miguel; Bode, Lars; Vos, De Willem; Gueimonde, Miguel; Margolles, Abelardo; Sinderen, Van Douwe; Ventura, Marco

2017-01-01

The human gut microbiota is engaged in multiple interactions affecting host health during the host's entire life span. Microbes colonize the neonatal gut immediately following birth. The establishment and interactive development of this early gut microbiota are believed to be (at least partially)

Incorporating the gut microbiota into models of human and non-human primate ecology and evolution.

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Amato, Katherine R

2016-01-01

The mammalian gut is home to a diverse community of microbes. Advances in technology over the past two decades have allowed us to examine this community, the gut microbiota, in more detail, revealing a wide range of influences on host nutrition, health, and behavior. These host-gut microbe interactions appear to shape host plasticity and fitness in a variety of contexts, and therefore represent a key factor missing from existing models of human and non-human primate ecology and evolution. However, current studies of the gut microbiota tend to include limited contextual data or are clinical, making it difficult to directly test broad anthropological hypotheses. Here, I review what is known about the animal gut microbiota and provide examples of how gut microbiota research can be integrated into the study of human and non-human primate ecology and evolution with targeted data collection. Specifically, I examine how the gut microbiota may impact primate diet, energetics, disease resistance, and cognition. While gut microbiota research is proliferating rapidly, especially in the context of humans, there remain important gaps in our understanding of host-gut microbe interactions that will require an anthropological perspective to fill. Likewise, gut microbiota research will be an important tool for filling remaining gaps in anthropological research. © 2016 Wiley Periodicals, Inc.

Advances and perspectives in in vitro human gut fermentation modeling.

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Payne, Amanda N; Zihler, Annina; Chassard, Christophe; Lacroix, Christophe

2012-01-01

The gut microbiota is a highly specialized organ containing host-specific assemblages of microbes whereby metabolic activity directly impacts human health and disease. In vitro gut fermentation models present an unmatched opportunity of performing studies frequently challenged in humans and animals owing to ethical concerns. Multidisciplinary systems biology analyses supported by '-omics' platforms remain widely neglected in the field of in vitro gut fermentation modeling but are key to advancing the significance of these models. Model-driven experimentation using a combination of in vitro gut fermentation and in vitro human cell models represent an advanced approach in identifying complex host-microbe interactions and niches central to gut fermentation processes. The aim of this review is to highlight the advances and challenges exhibited by in vitro human gut fermentation modeling. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

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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.

Human gut microbiome viewed across age and geography

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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...

Challenges of metabolomics in human gut microbiota research.

Science.gov (United States)

Smirnov, Kirill S; Maier, Tanja V; Walker, Alesia; Heinzmann, Silke S; Forcisi, Sara; Martinez, Inés; Walter, Jens; Schmitt-Kopplin, Philippe

2016-08-01

The review highlights the role of metabolomics in studying human gut microbial metabolism. Microbial communities in our gut exert a multitude of functions with huge impact on human health and disease. Within the meta-omics discipline, gut microbiome is studied by (meta)genomics, (meta)transcriptomics, (meta)proteomics and metabolomics. The goal of metabolomics research applied to fecal samples is to perform their metabolic profiling, to quantify compounds and classes of interest, to characterize small molecules produced by gut microbes. Nuclear magnetic resonance spectroscopy and mass spectrometry are main technologies that are applied in fecal metabolomics. Metabolomics studies have been increasingly used in gut microbiota related research regarding health and disease with main focus on understanding inflammatory bowel diseases. The elucidated metabolites in this field are summarized in this review. We also addressed the main challenges of metabolomics in current and future gut microbiota research. The first challenge reflects the need of adequate analytical tools and pipelines, including sample handling, selection of appropriate equipment, and statistical evaluation to enable meaningful biological interpretation. The second challenge is related to the choice of the right animal model for studies on gut microbiota. We exemplified this using NMR spectroscopy for the investigation of cross-species comparison of fecal metabolite profiles. Finally, we present the problem of variability of human gut microbiota and metabolome that has important consequences on the concepts of personalized nutrition and medicine. Copyright © 2016 Elsevier GmbH. All rights reserved.

Mining the Human Gut Microbiota for Immunomodulatory Organisms.

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Geva-Zatorsky, Naama; Sefik, Esen; Kua, Lindsay; Pasman, Lesley; Tan, Tze Guan; Ortiz-Lopez, Adriana; Yanortsang, Tsering Bakto; Yang, Liang; Jupp, Ray; Mathis, Diane; Benoist, Christophe; Kasper, Dennis L

2017-02-23

Within the human gut reside diverse microbes coexisting with the host in a mutually advantageous relationship. Evidence has revealed the pivotal role of the gut microbiota in shaping the immune system. To date, only a few of these microbes have been shown to modulate specific immune parameters. Herein, we broadly identify the immunomodulatory effects of phylogenetically diverse human gut microbes. We monocolonized mice with each of 53 individual bacterial species and systematically analyzed host immunologic adaptation to colonization. Most microbes exerted several specialized, complementary, and redundant transcriptional and immunomodulatory effects. Surprisingly, these were independent of microbial phylogeny. Microbial diversity in the gut ensures robustness of the microbiota's ability to generate a consistent immunomodulatory impact, serving as a highly important epigenetic system. This study provides a foundation for investigation of gut microbiota-host mutualism, highlighting key players that could identify important therapeutics. Copyright © 2017 Elsevier Inc. All rights reserved.

Shotgun metaproteomics of the human distal gut microbiota

Energy Technology Data Exchange (ETDEWEB)

VerBerkmoes, N.C.; Russell, A.L.; Shah, M.; Godzik, A.; Rosenquist, M.; Halfvarsson, J.; Lefsrud, M.G.; Apajalahti, J.; Tysk, C.; Hettich, R.L.; Jansson, Janet K.

2008-10-15

The human gut contains a dense, complex and diverse microbial community, comprising the gut microbiome. Metagenomics has recently revealed the composition of genes in the gut microbiome, but provides no direct information about which genes are expressed or functioning. Therefore, our goal was to develop a novel approach to directly identify microbial proteins in fecal samples to gain information about the genes expressed and about key microbial functions in the human gut. We used a non-targeted, shotgun mass spectrometry-based whole community proteomics, or metaproteomics, approach for the first deep proteome measurements of thousands of proteins in human fecal samples, thus demonstrating this approach on the most complex sample type to date. The resulting metaproteomes had a skewed distribution relative to the metagenome, with more proteins for translation, energy production and carbohydrate metabolism when compared to what was earlier predicted from metagenomics. Human proteins, including antimicrobial peptides, were also identified, providing a non-targeted glimpse of the host response to the microbiota. Several unknown proteins represented previously undescribed microbial pathways or host immune responses, revealing a novel complex interplay between the human host and its associated microbes.

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

The food-gut human axis: the effects of diet on gut microbiota and metabolome.

Science.gov (United States)

De Angelis, Maria; Garruti, Gabriella; Minervini, Fabio; Bonfrate, Leonilde; Portincasa, Piero; Gobbetti, Marco

2017-04-27

Gut microbiota, the largest symbiont community hosted in human organism, is emerging as a pivotal player in the relationship between dietary habits and health. Oral and, especially, intestinal microbes metabolize dietary components, affecting human health by producing harmful or beneficial metabolites, which are involved in the incidence and progression of several intestinal related and non-related diseases. Habitual diet (Western, Agrarian and Mediterranean omnivore diets, vegetarian, vegan and gluten-free diets) drives the composition of the gut microbiota and metabolome. Within the dietary components, polymers (mainly fibers, proteins, fat and polyphenols) that are not hydrolyzed by human enzymes seem to be the main leads of the metabolic pathways of gut microbiota, which in turn directly influences the human metabolome. Specific relationships between diet and microbes, microbes and metabolites, microbes and immune functions and microbes and/or their metabolites and some human diseases are being established. Dietary treatments with fibers are the most effective to benefit the metabolome profile, by improving the synthesis of short chain fatty acids and decreasing the level of molecules, such as p-cresyl sulfate, indoxyl sulfate and trimethylamine N-oxide, involved in disease state. Based on the axis diet-microbiota-health, this review aims at describing the most recent knowledge oriented towards a profitable use of diet to provide benefits to human health, both directly and indirectly, through the activity of gut microbiota. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

How informative is the mouse for human gut microbiota research?

Science.gov (United States)

Nguyen, Thi Loan Anh; Vieira-Silva, Sara; Liston, Adrian; Raes, Jeroen

2015-01-01

The microbiota of the human gut is gaining broad attention owing to its association with a wide range of diseases, ranging from metabolic disorders (e.g. obesity and type 2 diabetes) to autoimmune diseases (such as inflammatory bowel disease and type 1 diabetes), cancer and even neurodevelopmental disorders (e.g. autism). Having been increasingly used in biomedical research, mice have become the model of choice for most studies in this emerging field. Mouse models allow perturbations in gut microbiota to be studied in a controlled experimental setup, and thus help in assessing causality of the complex host-microbiota interactions and in developing mechanistic hypotheses. However, pitfalls should be considered when translating gut microbiome research results from mouse models to humans. In this Special Article, we discuss the intrinsic similarities and differences that exist between the two systems, and compare the human and murine core gut microbiota based on a meta-analysis of currently available datasets. Finally, we discuss the external factors that influence the capability of mouse models to recapitulate the gut microbiota shifts associated with human diseases, and investigate which alternative model systems exist for gut microbiota research. © 2015. Published by The Company of Biologists Ltd.

The human gut virome: a multifaceted majority

Directory of Open Access Journals (Sweden)

Lesley Ann Ogilvie

2015-09-01

Full Text Available Here we outline our current understanding of the human gut virome, in particular the phage component of this ecosystem, highlighting progress and challenges in viral discovery in this arena. We reveal how developments in high-throughput sequencing technologies and associated data analysis methodologies are helping to illuminate this abundant ‘biological dark matter’. Current evidence suggests that the human gut virome is a highly individual but temporally stable collective, dominated by phage exhibiting a temperate lifestyle. This viral community also appears to encode a surprisingly rich functional repertoire that confers a range of attributes to their bacterial hosts, ranging from bacterial virulence and pathogenesis to maintaining host-microbiome stability and community resilience. Despite the significant advances in our understanding of the gut virome in recent years, it is clear that we remain in a period of discovery and revelation, as new methods and technologies begin to provide deeper understanding of the inherent ecological characteristics of this viral ecosystem. As our understanding increases, the nature of the multi-partite interactions occurring between host and microbiome will become clearer, helping us to more rationally define the concepts and principles that will underpin approaches to using human gut virome components for medical or biotechnological applications.

Genomic variation landscape of the human gut microbiome

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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...

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...

Evolutionary and ecological forces that shape the bacterial communities of the human gut

Science.gov (United States)

Messer, Jeannette S.; Liechty, Emma R; Vogel, Olivia A.; Chang, Eugene B.

2017-01-01

Since microbes were first described in the mid-1600's, we have come to appreciate that they live all around and within us with both beneficial and detrimental effects on nearly every aspect of our lives. The human gastrointestinal tract is inhabited by a dynamic community of trillions of bacteria that constantly interact with each other and their human host. The acquisition of these bacteria is not stochastic, but determined by circumstance (environment), host rules (genetics, immune state, mucus, etc), and dynamic self-selection among microbes to form stable, resilient communities that are in balance with the host. In this review, we will discuss how these factors lead to formation of the gut bacterial community and influence its interactions with the host. We will also address how gut bacteria contribute to disease and how they could potentially be targeted to prevent and treat a variety of human ailments. PMID:28145439

Human gut microbiota and healthy aging: Recent developments and future prospective.

Science.gov (United States)

Kumar, Manish; Babaei, Parizad; Ji, Boyang; Nielsen, Jens

2016-10-27

The human gut microbiota alters with the aging process. In the first 2-3 years of life, the gut microbiota varies extensively in composition and metabolic functions. After this period, the gut microbiota demonstrates adult-like more stable and diverse microbial species. However, at old age, deterioration of physiological functions of the human body enforces the decrement in count of beneficial species (e.g. Bifidobacteria ) in the gut microbiota, which promotes various gut-related diseases (e.g. inflammatory bowel disease). Use of plant-based diets and probiotics/prebiotics may elevate the abundance of beneficial species and prevent gut-related diseases. Still, the connections between diet, microbes, and host are only partially known. To this end, genome-scale metabolic modeling can help to explore these connections as well as to expand the understanding of the metabolic capability of each species in the gut microbiota. This systems biology approach can also predict metabolic variations in the gut microbiota during ageing, and hereby help to design more effective probiotics/prebiotics.

Low calorie sweeteners: Evidence remains lacking for effects on human gut function.

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Bryant, Charlotte; Mclaughlin, John

2016-10-01

The importance of nutrient induced gut-brain signalling in the regulation of human food intake has become an increasing focus of research. Much of the caloric excess consumed comes from dietary sugars, but our knowledge about the mechanisms mediating the physiological and appetitive effects of sweet tastants in the human gut and gut-brain axis is far from complete. The comparative effects of natural sugars vs low calorie sweeteners are also poorly understood. Research in animal and cellular models has suggested a key functional role in gut endocrine cells for the sweet taste receptors previously well described in oral taste. However human studies to date have very consistently failed to show that activation of the sweet taste receptor by low calorie sweeteners placed in the human gut fails to replicate any of the effects on gastric motility, gut hormones or appetitive responses evoked by caloric sugars. Copyright © 2016. Published by Elsevier Inc.

Experimental Approaches for Defining Functional Roles of Microbes in the Human Gut

DEFF Research Database (Denmark)

Dantas, Gautam; Sommer, Morten; Degnan, Patrick H.

2013-01-01

The complex and intimate relationship between humans and their gut microbial communities is becoming less obscure, due in part to large-scale gut microbial genome-sequencing projects and culture-independent surveys of the composition and gene content of these communities.These studies build upon...... ofmicrobial genome and community profiling projects, and the loss-of-function and gain-of-function strategies long employed in model organisms are now being extended to microbial genes, species, and communities from the human gut. These developments promise to deepen our understanding of human gut host...

Metaproteomic analysis of human gut microbiota: where are we heading?

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Lee, Pey Yee; Chin, Siok-Fong; Neoh, Hui-Min; Jamal, Rahman

2017-06-12

The human gut is home to complex microbial populations that change dynamically in response to various internal and external stimuli. The gut microbiota provides numerous functional benefits that are crucial for human health but in the setting of a disturbed equilibrium, the microbial community can cause deleterious outcomes such as diseases and cancers. Characterization of the functional activities of human gut microbiota is fundamental to understand their roles in human health and disease. Metaproteomics, which refers to the study of the entire protein collection of the microbial community in a given sample is an emerging area of research that provides informative details concerning functional aspects of the microbiota. In this mini review, we present a summary of the progress of metaproteomic analysis for studying the functional role of gut microbiota. This is followed by an overview of the experimental approaches focusing on fecal specimen for metaproteomics and is concluded by a discussion on the challenges and future directions of metaproteomic research.

The First Microbial Colonizers of the Human Gut: Composition, Activities, and Health Implications of the Infant Gut Microbiota.

Science.gov (United States)

Milani, Christian; Duranti, Sabrina; Bottacini, Francesca; Casey, Eoghan; Turroni, Francesca; Mahony, Jennifer; Belzer, Clara; Delgado Palacio, Susana; Arboleya Montes, Silvia; Mancabelli, Leonardo; Lugli, Gabriele Andrea; Rodriguez, Juan Miguel; Bode, Lars; de Vos, Willem; Gueimonde, Miguel; Margolles, Abelardo; van Sinderen, Douwe; Ventura, Marco

2017-12-01

The human gut microbiota is engaged in multiple interactions affecting host health during the host's entire life span. Microbes colonize the neonatal gut immediately following birth. The establishment and interactive development of this early gut microbiota are believed to be (at least partially) driven and modulated by specific compounds present in human milk. It has been shown that certain genomes of infant gut commensals, in particular those of bifidobacterial species, are genetically adapted to utilize specific glycans of this human secretory fluid, thus representing a very intriguing example of host-microbe coevolution, where both partners are believed to benefit. In recent years, various metagenomic studies have tried to dissect the composition and functionality of the infant gut microbiome and to explore the distribution across the different ecological niches of the infant gut biogeography of the corresponding microbial consortia, including those corresponding to bacteria and viruses, in healthy and ill subjects. Such analyses have linked certain features of the microbiota/microbiome, such as reduced diversity or aberrant composition, to intestinal illnesses in infants or disease states that are manifested at later stages of life, including asthma, inflammatory bowel disease, and metabolic disorders. Thus, a growing number of studies have reported on how the early human gut microbiota composition/development may affect risk factors related to adult health conditions. This concept has fueled the development of strategies to shape the infant microbiota composition based on various functional food products. In this review, we describe the infant microbiota, the mechanisms that drive its establishment and composition, and how microbial consortia may be molded by natural or artificial interventions. Finally, we discuss the relevance of key microbial players of the infant gut microbiota, in particular bifidobacteria, with respect to their role in health and

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...

Prevalence of Antibiotic Resistance Genes among Human Gut-Derived Bifidobacteria.

Science.gov (United States)

Duranti, Sabrina; Lugli, Gabriele Andrea; Mancabelli, Leonardo; Turroni, Francesca; Milani, Christian; Mangifesta, Marta; Ferrario, Chiara; Anzalone, Rosaria; Viappiani, Alice; van Sinderen, Douwe; Ventura, Marco

2017-02-01

The microbiota of the human gastrointestinal tract (GIT) may regularly be exposed to antibiotics, which are used to prevent and treat infectious diseases caused by bacteria and fungi. Bacterial communities of the gut retain a reservoir of antibiotic resistance (AR) genes, and antibiotic therapy thus positively selects for those microorganisms that harbor such genetic features, causing microbiota modulation. During the first months following birth, bifidobacteria represent some of the most dominant components of the human gut microbiota, although little is known about their AR gene complement (or resistome). In the current study, we assessed the resistome of the Bifidobacterium genus based on phenotypic and genotypic data of members that represent all currently recognized bifidobacterial (sub)species. Moreover, a comparison between the bifidobacterial resistome and gut metagenome data sets from adults and infants shows that the bifidobacterial community present at the first week following birth possesses a reduced AR arsenal compared to that present in the infant bifidobacterial population in subsequent weeks of the first year of life. Our findings reinforce the concept that the early infant gut microbiota is more susceptible to disturbances by antibiotic treatment than the gut microbiota developed at a later life stage. The spread of resistance to antibiotics among bacterial communities has represented a major concern since their discovery in the last century. The risk of genetic transfer of resistance genes between microorganisms has been extensively investigated due to its relevance to human health. In contrast, there is only limited information available on antibiotic resistance among human gut commensal microorganisms such as bifidobacteria, which are widely exploited by the food industry as health-promoting microorganisms or probiotic ingredients. In the current study, we explored the occurrence of antibiotic resistance genes in the genomes of bifidobacteria

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.

Human symbionts inject and neutralize antibacterial toxins to persist in the gut.

Science.gov (United States)

Wexler, Aaron G; Bao, Yiqiao; Whitney, John C; Bobay, Louis-Marie; Xavier, Joao B; Schofield, Whitman B; Barry, Natasha A; Russell, Alistair B; Tran, Bao Q; Goo, Young Ah; Goodlett, David R; Ochman, Howard; Mougous, Joseph D; Goodman, Andrew L

2016-03-29

The human gut microbiome is a dynamic and densely populated microbial community that can provide important benefits to its host. Cooperation and competition for nutrients among its constituents only partially explain community composition and interpersonal variation. Notably, certain human-associated Bacteroidetes--one of two major phyla in the gut--also encode machinery for contact-dependent interbacterial antagonism, but its impact within gut microbial communities remains unknown. Here we report that prominent human gut symbionts persist in the gut through continuous attack on their immediate neighbors. Our analysis of just one of the hundreds of species in these communities reveals 12 candidate antibacterial effector loci that can exist in 32 combinations. Through the use of secretome studies, in vitro bacterial interaction assays and multiple mouse models, we uncover strain-specific effector/immunity repertoires that can predict interbacterial interactions in vitro and in vivo, and find that some of these strains avoid contact-dependent killing by accumulating immunity genes to effectors that they do not encode. Effector transmission rates in live animals can exceed 1 billion events per minute per gram of colonic contents, and multiphylum communities of human gut commensals can partially protect sensitive strains from these attacks. Together, these results suggest that gut microbes can determine their interactions through direct contact. An understanding of the strategies human gut symbionts have evolved to target other members of this community may provide new approaches for microbiome manipulation.

Bacteria from diverse habitats colonize and compete in the mouse gut.

Science.gov (United States)

Seedorf, Henning; Griffin, Nicholas W; Ridaura, Vanessa K; Reyes, Alejandro; Cheng, Jiye; Rey, Federico E; Smith, Michelle I; Simon, Gabriel M; Scheffrahn, Rudolf H; Woebken, Dagmar; Spormann, Alfred M; Van Treuren, William; Ursell, Luke K; Pirrung, Megan; Robbins-Pianka, Adam; Cantarel, Brandi L; Lombard, Vincent; Henrissat, Bernard; Knight, Rob; Gordon, Jeffrey I

2014-10-09

To study how microbes establish themselves in a mammalian gut environment, we colonized germ-free mice with microbial communities from human, zebrafish, and termite guts, human skin and tongue, soil, and estuarine microbial mats. Bacteria from these foreign environments colonized and persisted in the mouse gut; their capacity to metabolize dietary and host carbohydrates and bile acids correlated with colonization success. Cohousing mice harboring these xenomicrobiota or a mouse cecal microbiota, along with germ-free "bystanders," revealed the success of particular bacterial taxa in invading guts with established communities and empty gut habitats. Unanticipated patterns of ecological succession were observed; for example, a soil-derived bacterium dominated even in the presence of bacteria from other gut communities (zebrafish and termite), and human-derived bacteria colonized germ-free bystander mice before mouse-derived organisms. This approach can be generalized to address a variety of mechanistic questions about succession, including succession in the context of microbiota-directed therapeutics. Copyright © 2014 Elsevier Inc. All rights reserved.

Soy and Gut Microbiota: Interaction and Implication for Human Health.

Science.gov (United States)

Huang, Haiqiu; Krishnan, Hari B; Pham, Quynhchi; Yu, Liangli Lucy; Wang, Thomas T Y

2016-11-23

Soy (Glycine max) is a major commodity in the United States, and soy foods are gaining popularity due to their reported health-promoting effects. In the past two decades, soy and soy bioactive components have been studied for their health-promoting/disease-preventing activities and potential mechanisms of action. Recent studies have identified gut microbiota as an important component in the human body ecosystem and possibly a critical modulator of human health. Soy foods' interaction with the gut microbiota may critically influence many aspects of human development, physiology, immunity, and nutrition at different stages of life. This review summarizes current knowledge on the effects of soy foods and soy components on gut microbiota population and composition. It was found, although results vary in different studies, in general, both animal and human studies have shown that consumption of soy foods can increase the levels of bifidobacteria and lactobacilli and alter the ratio between Firmicutes and Bacteroidetes. These changes in microbiota are consistent with reported reductions in pathogenic bacteria populations in the gut, thereby lowering the risk of diseases and leading to beneficial effects on human health.

Starch and starch hydrolysates are favorable carbon sources for bifidobacteria in the human gut.

Science.gov (United States)

Liu, Songling; Ren, Fazheng; Zhao, Liang; Jiang, Lu; Hao, Yanling; Jin, Junhua; Zhang, Ming; Guo, Huiyuan; Lei, Xingen; Sun, Erna; Liu, Hongna

2015-03-01

Bifidobacteria are key commensals in human gut, and their abundance is associated with the health of their hosts. Although they are dominant in infant gut, their number becomes lower in adult gut. The changes of the diet are considered to be main reason for this difference. Large amounts of whole-genomic sequence data of bifidobacteria make it possible to elucidate the genetic interpretation of their adaptation to the nutrient environment. Among the nutrients in human gut, starch is a highly fermentable substrate and can exert beneficial effects by increasing bifidobacteria and/or being fermented to short chain fatty acids. In order to determine the potential substrate preference of bifidobacteria, we compared the glycoside hydrolase (GH) profiles of a pooled-bifidobacterial genome (PBG) with a representative microbiome (RM) of the human gut. In bifidobacterial genomes, only 15% of GHs contained signal peptides, suggesting their weakness in utilization of complex carbohydrate, such as plant cell wall polysaccharides. However, compared with other intestinal bacteria, bifidobacteiral genomes encoded more GH genes for degrading starch and starch hydrolysates, indicating that they have genetic advantages in utilizing these substrates. Bifidobacterium longum subsp. longum BBMN68 isolated from centenarian's faeces was used as a model strain to further investigate the carbohydrate utilization. The pathway for degrading starch and starch hydrolysates was the only complete pathway for complex carbohydrates in human gut. It is noteworthy that all of the GH genes for degrading starch and starch hydrolysates in the BBMN68 genome were conserved in all studied bifidobacterial strains. The in silico analyses of BBMN68 were further confirmed by growth experiments, proteomic and real-time quantitative PCR (RT-PCR) analyses. Our results demonstrated that starch and starch hydrolysates were the most universal and favorable carbon sources for bifidobacteria. The low amount of these

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....

Meta genome-wide network from functional linkages of genes in human gut microbial ecosystems.

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Ji, Yan; Shi, Yixiang; Wang, Chuan; Dai, Jianliang; Li, Yixue

2013-03-01

The human gut microbial ecosystem (HGME) exerts an important influence on the human health. In recent researches, meta-genomics provided deep insights into the HGME in terms of gene contents, metabolic processes and genome constitutions of meta-genome. Here we present a novel methodology to investigate the HGME on the basis of a set of functionally coupled genes regardless of their genome origins when considering the co-evolution properties of genes. By analyzing these coupled genes, we showed some basic properties of HGME significantly associated with each other, and further constructed a protein interaction map of human gut meta-genome to discover some functional modules that may relate with essential metabolic processes. Compared with other studies, our method provides a new idea to extract basic function elements from meta-genome systems and investigate complex microbial environment by associating its biological traits with co-evolutionary fingerprints encoded in it.

Effect of diet on the human gut microbiota

DEFF Research Database (Denmark)

Bahl, Martin Iain

The gut microbiota plays an important role for humans in both health and disease. It is therefore important to understand how and to what extent choice of diet may influence the microbial community and the effects this has on the host. The variation in the normal human gut microbiota may however...... impede the discovery of correlations between dietary changes and compositional shifts in the microbiota by masking such effects. Although specific functional food ingredients, such as prebiotics, are known to have measurable effects on e.g. abundance of bifidobacteria, it is nevertheless clear...... that induced shifts in gut microbiota show large inter-individual variations. It thus seems plausible that knowing the microbiota composition could facilitate predictions as to how the community will react to dietary interventions thus moving towards some degree of personalised dietary recommendations. During...

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

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...

The Human Gut Antibiotic Resistome in the Metagenomic Era: Progress and Perspectives

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Yongfei Hu

2016-04-01

Full Text Available The human gut is populated by a vast number of bacteria, which play a critical role in human health. In recent years, attention has focused on the gut bacteria as a reservoir of antibiotic resistance genes (ARGs. Both culture-dependent and culture-independent methods have been applied to investigate numerous ARGs, collectively called the antibiotic resistome, harbored by gut bacteria. This has led to an increased understanding of the overall profile of the gut antibiotic resistome, although it remains incompletely understood. In this review, we summarize the recent research findings on the human gut antibiotic resistome, with an emphasis on progress achieved using the culture-independent metagenomic strategy. We also describe the features of different available ARG databases used for annotation in metagenomic analysis, discuss the potential problems and limitations in current research, and suggest several directions for future investigation.

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

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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

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

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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.

Human Gut-Derived Commensal Bacteria Suppress CNS Inflammatory and Demyelinating Disease.

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Mangalam, Ashutosh; Shahi, Shailesh K; Luckey, David; Karau, Melissa; Marietta, Eric; Luo, Ningling; Choung, Rok Seon; Ju, Josephine; Sompallae, Ramakrishna; Gibson-Corley, Katherine; Patel, Robin; Rodriguez, Moses; David, Chella; Taneja, Veena; Murray, Joseph

2017-08-08

The human gut is colonized by a large number of microorganisms (∼10 13 bacteria) that support various physiologic functions. A perturbation in the healthy gut microbiome might lead to the development of inflammatory diseases, such as multiple sclerosis (MS). Therefore, gut commensals might provide promising therapeutic options for treating MS and other diseases. We report the identification of human gut-derived commensal bacteria, Prevotella histicola, which can suppress experimental autoimmune encephalomyelitis (EAE) in a human leukocyte antigen (HLA) class II transgenic mouse model. P. histicola suppresses disease through the modulation of systemic immune responses. P. histicola challenge led to a decrease in pro-inflammatory Th1 and Th17 cells and an increase in the frequencies of CD4 + FoxP3 + regulatory T cells, tolerogenic dendritic cells, and suppressive macrophages. Our study provides evidence that the administration of gut commensals may regulate a systemic immune response and may, therefore, have a possible role in treatment strategies for MS. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

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.

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....

From Network Analysis to Functional Metabolic Modeling of the Human Gut Microbiota.

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Bauer, Eugen; Thiele, Ines

2018-01-01

An important hallmark of the human gut microbiota is its species diversity and complexity. Various diseases have been associated with a decreased diversity leading to reduced metabolic functionalities. Common approaches to investigate the human microbiota include high-throughput sequencing with subsequent correlative analyses. However, to understand the ecology of the human gut microbiota and consequently design novel treatments for diseases, it is important to represent the different interactions between microbes with their associated metabolites. Computational systems biology approaches can give further mechanistic insights by constructing data- or knowledge-driven networks that represent microbe interactions. In this minireview, we will discuss current approaches in systems biology to analyze the human gut microbiota, with a particular focus on constraint-based modeling. We will discuss various community modeling techniques with their advantages and differences, as well as their application to predict the metabolic mechanisms of intestinal microbial communities. Finally, we will discuss future perspectives and current challenges of simulating realistic and comprehensive models of the human gut microbiota.

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...

The role of gut microbiota in health and disease: In vitro modeling of host-microbe interactions at the aerobe-anaerobe interphase of the human gut.

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von Martels, Julius Z H; Sadaghian Sadabad, Mehdi; Bourgonje, Arno R; Blokzijl, Tjasso; Dijkstra, Gerard; Faber, Klaas Nico; Harmsen, Hermie J M

2017-04-01

The microbiota of the gut has many crucial functions in human health. Dysbiosis of the microbiota has been correlated to a large and still increasing number of diseases. Recent studies have mostly focused on analyzing the associations between disease and an aberrant microbiota composition. Functional studies using (in vitro) gut models are required to investigate the precise interactions that occur between specific bacteria (or bacterial mixtures) and gut epithelial cells. As most gut bacteria are obligate or facultative anaerobes, studying their effect on oxygen-requiring human gut epithelial cells is technically challenging. Still, several (anaerobic) bacterial-epithelial co-culture systems have recently been developed that mimic host-microbe interactions occurring in the human gut, including 1) the Transwell "apical anaerobic model of the intestinal epithelial barrier", 2) the Host-Microbiota Interaction (HMI) module, 3) the "Human oxygen-Bacteria anaerobic" (HoxBan) system, 4) the human gut-on-a-chip and 5) the HuMiX model. This review discusses the role of gut microbiota in health and disease and gives an overview of the characteristics and applications of these novel host-microbe co-culture systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Contribution of diet to the composition of the human gut microbiota.

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Graf, Daniela; Di Cagno, Raffaella; Fåk, Frida; Flint, Harry J; Nyman, Margareta; Saarela, Maria; Watzl, Bernhard

2015-01-01

In the human gut, millions of bacteria contribute to the microbiota, whose composition is specific for every individual. Although we are just at the very beginning of understanding the microbiota concept, we already know that the composition of the microbiota has a profound impact on human health. A key factor in determining gut microbiota composition is diet. Preliminary evidence suggests that dietary patterns are associated with distinct combinations of bacteria in the intestine, also called enterotypes. Western diets result in significantly different microbiota compositions than traditional diets. It is currently unknown which food constituents specifically promote growth and functionality of beneficial bacteria in the intestine. The aim of this review is to summarize the recently published evidence from human in vivo studies on the gut microbiota-modulating effects of diet. It includes sections on dietary patterns (e.g. Western diet), whole foods, food constituents, as wells as food-associated microbes and their influence on the composition of human gut microbiota. The conclusions highlight the problems faced by scientists in this fast-developing field of research, and the need for high-quality, large-scale human dietary intervention studies.

Food additives, contaminants and other minor components: effects on human gut microbiota-a review.

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Roca-Saavedra, Paula; Mendez-Vilabrille, Veronica; Miranda, Jose Manuel; Nebot, Carolina; Cardelle-Cobas, Alejandra; Franco, Carlos M; Cepeda, Alberto

2018-02-01

Gut bacteria play an important role in several metabolic processes and human diseases, such as obesity and accompanying co-morbidities, such as fatty liver disease, insulin resistance/diabetes, and cardiovascular events. Among other factors, dietary patterns, probiotics, prebiotics, synbiotics, antibiotics, and non-dietary factors, such as stress, age, exercise, and climatic conditions, can dramatically impact the human gut microbiota equilibrium and diversity. However, the effect of minor food constituents, including food additives and trace contaminants, on human gut microbiota has received less attention. Consequently, the present review aimed to provide an objective perspective of the current knowledge regarding the impacts of minor food constituents on human gut microbiota and consequently, on human health.

The obese gut microbiome across the epidemiologic transition

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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.

Comparative genome analysis of Megasphaera sp. reveals niche specialization and its potential role in the human gut.

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Sudarshan Anand Shetty

Full Text Available With increasing number of novel bacteria being isolated from the human gut ecosystem, there is a greater need to study their role in the gut ecosystem and their effect on the host health. In the present study, we carried out in silico genome-wide analysis of two novel Megasphaera sp. isolates NM10 (DSM25563 and BL7 (DSM25562, isolated from feces of two healthy individuals and validated the key features by in vitro studies. The analysis revealed the general metabolic potential, adaptive features and the potential effects of these isolates on the host. The comparative genome analysis of the two human gut isolates NM10 and BL7 with ruminal isolate Megasphaera elsdenii (DSM20460 highlighted the differential adaptive features for their survival in human gut. The key findings include features like bile resistance, presence of various sensory and regulatory systems, stress response systems, membrane transporters and resistance to antibiotics. Comparison of the "glycobiome" based on the genomes of the ruminal isolate with the human gut isolates NM10 and BL revealed the presence of diverse and unique sets of Carbohydrate-Active enzymes (CAZymes amongst these isolates, with a higher collection of CAZymes in the human gut isolates. This could be attributed to the difference in host diet and thereby the environment, consequently suggesting host specific adaptation in these isolates. In silico analysis of metabolic potential predicted the ability of these isolates to produce important metabolites like short chain fatty acids (butyrate, acetate, formate, and caproate, vitamins and essential amino acids, which was further validated by in vitro experiments. The ability of these isolates to produce important metabolites advocates for a potential healthy influence on the host. Further in vivo studies including transcriptomic and proteomic analysis will be required for better understanding the role and impact of these Megasphaera sp. isolates NM10 and BL7 on the

Survival of Yogurt Bacteria in the Human Gut

OpenAIRE

Elli, Marina; Callegari, Maria Luisa; Ferrari, Susanna; Bessi, Elena; Cattivelli, Daniela; Soldi, Sara; Morelli, Lorenzo; Goupil Feuillerat, Nathalie; Antoine, Jean-Michel

2006-01-01

Whether Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus can be recovered after passage through the human gut was tested by feeding 20 healthy volunteers commercial yogurt. Yogurt bacteria were found in human feces, suggesting that they can survive transit in the gastrointestinal tract.

Anaerobic 4-hydroxyproline utilization: Discovery of a new glycyl radical enzyme in the human gut microbiome uncovers a widespread microbial metabolic activity.

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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.

Metabolic niche of a prominent sulfate-reducing human gut bacterium

OpenAIRE

Rey, Federico E.; Gonzalez, Mark D.; Cheng, Jiye; Wu, Meng; Ahern, Philip P.; Gordon, Jeffrey I.

2013-01-01

Sulfate-reducing bacteria (SRB) colonize the guts of ∼50% of humans. We used genome-wide transposon mutagenesis and insertion-site sequencing, RNA-Seq, plus mass spectrometry to characterize genetic and environmental factors that impact the niche of Desulfovibrio piger, the most common SRB in a surveyed cohort of healthy US adults. Gnotobiotic mice were colonized with an assemblage of sequenced human gut bacterial species with or without D. piger and fed diets with different levels and types ...

Survival of Yogurt Bacteria in the Human Gut

Science.gov (United States)

Elli, Marina; Callegari, Maria Luisa; Ferrari, Susanna; Bessi, Elena; Cattivelli, Daniela; Soldi, Sara; Morelli, Lorenzo; Goupil Feuillerat, Nathalie; Antoine, Jean-Michel

2006-01-01

Whether Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus thermophilus can be recovered after passage through the human gut was tested by feeding 20 healthy volunteers commercial yogurt. Yogurt bacteria were found in human feces, suggesting that they can survive transit in the gastrointestinal tract. PMID:16820518

Changes in human gut flora with age: an Indian familial study.

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Marathe, Nachiket; Shetty, Sudarshan; Lanjekar, Vikram; Ranade, Dilip; Shouche, Yogesh

2012-09-26

The gut micro flora plays vital role in health status of the host. The majority of microbes residing in the gut have a profound influence on human physiology and nutrition. Different human ethnic groups vary in genetic makeup as well as the environmental conditions they live in. The gut flora changes with genetic makeup and environmental factors and hence it is necessary to understand the composition of gut flora of different ethnic groups. Indian population is different in physiology from western population (YY paradox) and thus the gut flora in Indian population is likely to differ from the extensively studied gut flora in western population. In this study we have investigated the gut flora of two Indian families, each with three individuals belonging to successive generations and living under the same roof. Denaturation gradient gel electrophoresis analysis showed age-dependant variation in gut microflora amongst the individuals within a family. Different bacterial genera were dominant in the individual of varying age in clone library analysis. Obligate anaerobes isolated from individuals within a family showed age related differences in isolation pattern, with 27% (6 out of 22) of the isolates being potential novel species based on 16S rRNA gene sequence. In qPCR a consistent decrease in Firmicutes number and increase in Bacteroidetes number with increasing age was observed in our subjects, this pattern of change in Firmicutes / Bacteroidetes ratio with age is different than previously reported in European population. There is change in gut flora with age amongst the individuals within a family. The isolation of high percent of novel bacterial species and the pattern of change in Firmicutes /Bacteroidetes ratio with age suggests that the composition of gut flora in Indian individuals may be different than the western population. Thus, further extensive study is needed to define the gut flora in Indian population.

Rapid changes in the gut microbiome during human evolution.

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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.

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.

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.

Ménage à trois in the human gut: interactions between host, bacteria and phages.

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Mirzaei, Mohammadali Khan; Maurice, Corinne F

2017-07-01

The human gut is host to one of the densest microbial communities known, the gut microbiota, which contains bacteria, archaea, viruses, fungi and other microbial eukaryotes. Bacteriophages in the gut are largely unexplored, despite their potential to regulate bacterial communities and thus human health. In addition to helping us understand gut homeostasis, applying an ecological perspective to the study of bacterial and phage communities in the gut will help us to understand how this microbial system functions. For example, temporal studies of bacteria, phages and host immune cells in the gut during health and disease could provide key information about disease development and inform therapeutic treatments, whereas understanding the regulation of the replication cycles of phages could help harness the gut microbiota to improve disease outcomes. As the most abundant biological entities in our gut, we must consider bacteriophages in our pursuit of personalized medicine.

Microbial metaproteomics for characterizing the range of metabolic functions and activities of human gut microbiota.

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Xiong, Weili; Abraham, Paul E; Li, Zhou; Pan, Chongle; Hettich, Robert L

2015-10-01

The human gastrointestinal tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome is not merely a collection of opportunistic parasites, but rather provides important functions to the host that are absolutely critical to many aspects of health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial metaproteomics provides the ability to characterize the human gut microbiota functions and metabolic activities at a remarkably deep level, revealing information about microbiome development and stability as well as their interactions with their human host. Generally, microbial and human proteins can be extracted and then measured by high performance MS-based proteomics technology. Here, we review the field of human gut microbiome metaproteomics, with a focus on the experimental and informatics considerations involved in characterizing systems ranging from low-complexity model gut microbiota in gnotobiotic mice, to the emerging gut microbiome in the GI tract of newborn human infants, and finally to an established gut microbiota in human adults. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Computational determination of the effects of virulent Escherichia coli and salmonella bacteriophages on human gut.

Science.gov (United States)

Mostafa, Marwa Mostafa; Nassef, Mohammad; Badr, Amr

2016-10-01

Salmonella and Escherichia coli are different types of bacteria that cause food poisoning in humans. In the elderly, infants and people with chronic conditions, it is very dangerous if Salmonella or E. coli gets into the bloodstream and then they must be treated by phage therapy. Treating Salmonella and E. coli by phage therapy affects the gut flora. This research paper presents a system for detecting the effects of virulent E. coli and Salmonella bacteriophages on human gut. A method based on Domain-Domain Interactions (DDIs) model is implemented in the proposed system to determine the interactions between the proteins of human gut bacteria and the proteins of bacteriophages that infect virulent E. coli and Salmonella. The system helps gastroenterologists to realize the effect of injecting bacteriophages that infect virulent E. coli and Salmonella on the human gut. By testing the system over Enterobacteria phage 933W, Enterobacteria phage VT2-Sa and Enterobacteria phage P22, it resulted in four interactions between the proteins of the bacteriophages that infect E. coli O157:H7, E. coli O104:H4 and Salmonella typhimurium and the proteins of human gut bacterium strains. Several effects were detected such as: antibacterial activity against a number of bacterial species in human gut, regulation of cellular differentiation and organogenesis during gut, lung, and heart development, ammonia assimilation in bacteria, yeasts, and plants, energizing defense system and its function in the detoxification of lipopolysaccharide, and in the prevention of bacterial translocation in human gut. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota.

Science.gov (United States)

Forslund, Kristoffer; Hildebrand, Falk; Nielsen, Trine; Falony, Gwen; Le Chatelier, Emmanuelle; Sunagawa, Shinichi; Prifti, Edi; Vieira-Silva, Sara; Gudmundsdottir, Valborg; Pedersen, Helle K; Arumugam, Manimozhiyan; Kristiansen, Karsten; Voigt, Anita Yvonne; Vestergaard, Henrik; Hercog, Rajna; Costea, Paul Igor; Kultima, Jens Roat; Li, Junhua; Jørgensen, Torben; Levenez, Florence; Dore, Joël; Nielsen, H Bjørn; Brunak, Søren; Raes, Jeroen; Hansen, Torben; Wang, Jun; Ehrlich, S Dusko; Bork, Peer; Pedersen, Oluf

2015-12-10

In recent years, several associations between common chronic human disorders and altered gut microbiome composition and function have been reported. 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 for treatment yielded divergent conclusions regarding its associated gut microbial dysbiosis. Here we show, using 784 available human gut metagenomes, how antidiabetic medication confounds these results, and analyse in detail the effects of the most widely used antidiabetic drug metformin. We provide support for microbial mediation of the therapeutic effects of metformin through short-chain fatty acid production, as well as for potential microbiota-mediated mechanisms behind known intestinal adverse effects in the form of a relative increase in abundance of Escherichia species. Controlling for metformin treatment, we report a unified signature of gut microbiome shifts in T2D with a depletion of butyrate-producing taxa. 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 of specific human diseases from those of medication.

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.

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.

Human gut microbes impact host serum metabolome and insulin sensitivity

DEFF Research Database (Denmark)

Pedersen, Helle Krogh; Gudmundsdottir, Valborg; Nielsen, Henrik Bjørn

2016-01-01

Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant individ......Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin......-resistant individuals is characterized by increased levels of branched-chain amino acids (BCAAs), which correlate with a gut microbiome that has an enriched biosynthetic potential for BCAAs and is deprived of genes encoding bacterial inward transporters for these amino acids. Prevotella copri and Bacteroides vulgatus...

Potential Effects of Horizontal Gene Exchange in the Human Gut.

Science.gov (United States)

Lerner, Aaron; Matthias, Torsten; Aminov, Rustam

2017-01-01

Many essential functions of the human body are dependent on the symbiotic microbiota, which is present at especially high numbers and diversity in the gut. This intricate host-microbe relationship is a result of the long-term coevolution between the two. While the inheritance of mutational changes in the host evolution is almost exclusively vertical, the main mechanism of bacterial evolution is horizontal gene exchange. The gut conditions, with stable temperature, continuous food supply, constant physicochemical conditions, extremely high concentration of microbial cells and phages, and plenty of opportunities for conjugation on the surfaces of food particles and host tissues, represent one of the most favorable ecological niches for horizontal gene exchange. Thus, the gut microbial system genetically is very dynamic and capable of rapid response, at the genetic level, to selection, for example, by antibiotics. There are many other factors to which the microbiota may dynamically respond including lifestyle, therapy, diet, refined food, food additives, consumption of pre- and probiotics, and many others. The impact of the changing selective pressures on gut microbiota, however, is poorly understood. Presumably, the gut microbiome responds to these changes by genetic restructuring of gut populations, driven mainly via horizontal gene exchange. Thus, our main goal is to reveal the role played by horizontal gene exchange in the changing landscape of the gastrointestinal microbiome and potential effect of these changes on human health in general and autoimmune diseases in particular.

Potential Effects of Horizontal Gene Exchange in the Human Gut

Directory of Open Access Journals (Sweden)

Aaron Lerner

2017-11-01

Full Text Available Many essential functions of the human body are dependent on the symbiotic microbiota, which is present at especially high numbers and diversity in the gut. This intricate host–microbe relationship is a result of the long-term coevolution between the two. While the inheritance of mutational changes in the host evolution is almost exclusively vertical, the main mechanism of bacterial evolution is horizontal gene exchange. The gut conditions, with stable temperature, continuous food supply, constant physicochemical conditions, extremely high concentration of microbial cells and phages, and plenty of opportunities for conjugation on the surfaces of food particles and host tissues, represent one of the most favorable ecological niches for horizontal gene exchange. Thus, the gut microbial system genetically is very dynamic and capable of rapid response, at the genetic level, to selection, for example, by antibiotics. There are many other factors to which the microbiota may dynamically respond including lifestyle, therapy, diet, refined food, food additives, consumption of pre- and probiotics, and many others. The impact of the changing selective pressures on gut microbiota, however, is poorly understood. Presumably, the gut microbiome responds to these changes by genetic restructuring of gut populations, driven mainly via horizontal gene exchange. Thus, our main goal is to reveal the role played by horizontal gene exchange in the changing landscape of the gastrointestinal microbiome and potential effect of these changes on human health in general and autoimmune diseases in particular.

Human gut microbiota plays a role in the metabolism of drugs.

Science.gov (United States)

Jourova, Lenka; Anzenbacher, Pavel; Anzenbacherova, Eva

2016-09-01

The gut microbiome, an aggregate genome of trillions of microorganisms residing in the human gastrointestinal tract, is now known to play a critical role in human health and predisposition to disease. It is also involved in the biotransformation of xenobiotics and several recent studies have shown that the gut microbiota can affect the pharmacokinetics of orally taken drugs with implications for their oral bioavailability. Review of Pubmed, Web of Science and Science Direct databases for the years 1957-2016. Recent studies make it clear that the human gut microbiota can play a major role in the metabolism of xenobiotics and, the stability and oral bioavailability of drugs. Over the past 50 years, more than 30 drugs have been identified as a substrate for intestinal bacteria. Questions concerning the impact of the gut microbiota on drug metabolism, remain unanswered or only partially answered, namely (i) what are the molecular mechanisms and which bacterial species are involved? (ii) What is the impact of host genotype and environmental factors on the composition and function of the gut microbiota, (iii) To what extent is the composition of the intestinal microbiome stable, transmissible, and resilient to perturbation? (iv) Has past exposure to a given drug any impact on future microbial response, and, if so, for how long? Answering such questions should be an integral part of pharmaceutical research and personalised health care.

Comparison of DNA extraction methods for human gut microbial community profiling.

Science.gov (United States)

Lim, Mi Young; Song, Eun-Ji; Kim, Sang Ho; Lee, Jangwon; Nam, Young-Do

2018-03-01

The human gut harbors a vast range of microbes that have significant impact on health and disease. Therefore, gut microbiome profiling holds promise for use in early diagnosis and precision medicine development. Accurate profiling of the highly complex gut microbiome requires DNA extraction methods that provide sufficient coverage of the original community as well as adequate quality and quantity. We tested nine different DNA extraction methods using three commercial kits (TianLong Stool DNA/RNA Extraction Kit (TS), QIAamp DNA Stool Mini Kit (QS), and QIAamp PowerFecal DNA Kit (QP)) with or without additional bead-beating step using manual or automated methods and compared them in terms of DNA extraction ability from human fecal sample. All methods produced DNA in sufficient concentration and quality for use in sequencing, and the samples were clustered according to the DNA extraction method. Inclusion of bead-beating step especially resulted in higher degrees of microbial diversity and had the greatest effect on gut microbiome composition. Among the samples subjected to bead-beating method, TS kit samples were more similar to QP kit samples than QS kit samples. Our results emphasize the importance of mechanical disruption step for a more comprehensive profiling of the human gut microbiome. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Role of the normal gut microbiota.

Science.gov (United States)

Jandhyala, Sai Manasa; Talukdar, Rupjyoti; Subramanyam, Chivkula; Vuyyuru, Harish; Sasikala, Mitnala; Nageshwar Reddy, D

2015-08-07

Relation between the gut microbiota and human health is being increasingly recognised. It is now well established that a healthy gut flora is largely responsible for overall health of the host. The normal human gut microbiota comprises of two major phyla, namely Bacteroidetes and Firmicutes. Though the gut microbiota in an infant appears haphazard, it starts resembling the adult flora by the age of 3 years. Nevertheless, there exist temporal and spatial variations in the microbial distribution from esophagus to the rectum all along the individual's life span. Developments in genome sequencing technologies and bioinformatics have now enabled scientists to study these microorganisms and their function and microbe-host interactions in an elaborate manner both in health and disease. The normal gut microbiota imparts specific function in host nutrient metabolism, xenobiotic and drug metabolism, maintenance of structural integrity of the gut mucosal barrier, immunomodulation, and protection against pathogens. Several factors play a role in shaping the normal gut microbiota. They include (1) the mode of delivery (vaginal or caesarean); (2) diet during infancy (breast milk or formula feeds) and adulthood (vegan based or meat based); and (3) use of antibiotics or antibiotic like molecules that are derived from the environment or the gut commensal community. A major concern of antibiotic use is the long-term alteration of the normal healthy gut microbiota and horizontal transfer of resistance genes that could result in reservoir of organisms with a multidrug resistant gene pool.

Bacteriophages in the human gut: Our fellow travelers throughout life and potential biomarkers of heath or disease.

Science.gov (United States)

Bakhshinejad, Babak; Ghiasvand, Saeedeh

2017-08-15

The gastrointestinal (GI) tract is populated by a huge variety of viruses. Bacterial viruses (bacteriophages) constitute the largest and the most unrecognized part of virome. The total bacteriophage community of the human gut is called phageome. Phages colonize the gut from the earliest moments of life and become our fellow travelers throughout life. Phageome seems to be unique to each individual and shows a high degree of interpersonal variation. In the healthy gut, a vast majority of phages have a lysogenic lifestyle. These prophages serve as a major respository of mobile genetic elements in the gut and play key roles in the exchange of genetic material between bacterial species via horizontal gene transfer (HGT). But, imbalance in the gut microbial community during dysbiosis, caused by diseases or environmental stresses such as antibiotics, is accompanied by induction of prophages leading to a decreased ratio of symbionts to pathobionts. Based on this, a diseased gut is transformed from an environment predominantly occupied by prophages to an ecosystem mostly inhabited by lytic phages. A growing body of evidence has provided support for the notion that phageome structure and composition change dependent on the physiological or pathological status of the body. This has been demonstrated by pronounced quantitative and qualitative differences between the phageome of healthy individuals and patients. Although many aspects of the contribution made by phages to human biology remain to be understood, recent findings favor the suggestion that phageome might represent potential to serve as a biomarker of health or disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of rearing environment on the gut antimicrobial responses of two broiler chicken lines.

Science.gov (United States)

Butler, Vanessa L; Mowbray, Catherine A; Cadwell, Kevin; Niranji, Sherko S; Bailey, Richard; Watson, Kellie A; Ralph, John; Hall, Judith

2016-10-01

To reduce the risk of enteric disease in poultry, knowledge of how bird gut innate defences mature with age while also responding to different rearing environments is necessary. In this study the gut innate responses of two phylogenetically distinct lines of poultry raised from hatch to 35days, in conditions mimicing high hygiene (HH) and low hygiene (LH) rearing environments, were compared. Analyses focussed on the proximal gut antimicrobial activities and the duodenal and caecal AvBD1, 4 and 10 defensin profiles. Variability in microbial killing was observed between individual birds in each of the two lines at all ages, but samples from day 0 birds (hatch) of both lines exhibited marked killing properties, Line X: 19±11% (SEM) and Line Y: 8.5±12% (SEM). By day 7 a relaxation in killing was observed with bacterial survival increased from 3 (Line Y (LY)) to 11 (Line X (LX)) fold in birds reared in the HH environment. A less marked response was observed in the LH environment and delayed until day 14. At day 35 the gut antimicrobial properties of the two lines were comparable. The AvBD 1, 4 and 10 data relating to the duodenal and caecal tissues of day 0, 7 and 35 birds LX and LY birds revealed gene expression trends specific to each line and to the different rearing environments although the data were confounded by inter-individual variability. In summary elevated AvBD1 duodenal expression was detected in day 0 and day 7 LX, but not LY birds, maintained in LH environments; Line X and Y duodenal AvBD4 profiles were detected in day 7 birds reared in both environments although duodenal AvBD10 expression was less sensitive to bird age and rearing background. Caecal AvBD1 expression was particularly evident in newly hatched birds. These data suggest that proximal gut antimicrobial activity is related to the bird rearing environments although the roles of the AvBDs in such activities require further investigation. Copyright © 2016. Published by Elsevier B.V.

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

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

Colonizing the embryonic zebrafish gut with anaerobic bacteria derived from the human gastrointestinal tract.

Science.gov (United States)

Toh, Michael C; Goodyear, Mara; Daigneault, Michelle; Allen-Vercoe, Emma; Van Raay, Terence J

2013-06-01

The zebrafish has become increasingly popular for microbiological research. It has been used as an infection model for a variety of pathogens, and is also emerging as a tool for studying interactions between a host and its resident microbial communities. The mouse microbiota has been transplanted into the zebrafish gut, but to our knowledge, there has been no attempt to introduce a bacterial community derived from the human gut. We explored two methods for colonizing the developing gut of 5-day-old germ-free zebrafish larvae with a defined anaerobic microbial community derived from a single human fecal sample. Both environmental exposure (static immersion) and direct microinjection into the gut resulted in the establishment of two species-Lactobacillus paracasei and Eubacterium limosum-from a community of 30 strains consisting of 22 anaerobic species. Of particular interest is E. limosum, which, as a strict anaerobe, represents a group of bacteria which until now have not been shown to colonize the developing zebrafish gut. Our success here indicates that further investigation of zebrafish as a tool for studying human gut microbial communities is warranted.

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...

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.

Molecular biological methods for studying the gut microbiota : the EU human gut flora project

NARCIS (Netherlands)

Blaut, M; Collins, MD; Welling, GW; Dore, J; van Loo, J; de Vos, W

Seven European laboratories co-operated in a joint project (FAIR CT97-3035) to develop, refine and apply molecular methods towards facilitating elucidation of the complex composition of the human intestinal microflora and to devise robust methodologies for monitoring the gut flora in response to

Discovery of intramolecular trans-sialidases in human gut microbiota suggests novel mechanisms of mucosal adaptation

Science.gov (United States)

Tailford, Louise E.; Owen, C. David; Walshaw, John; Crost, Emmanuelle H.; Hardy-Goddard, Jemma; Le Gall, Gwenaelle; de Vos, Willem M.; Taylor, Garry L.; Juge, Nathalie

2015-07-01

The gastrointestinal mucus layer is colonized by a dense community of microbes catabolizing dietary and host carbohydrates during their expansion in the gut. Alterations in mucosal carbohydrate availability impact on the composition of microbial species. Ruminococcus gnavus is a commensal anaerobe present in the gastrointestinal tract of >90% of humans and overrepresented in inflammatory bowel diseases (IBD). Using a combination of genomics, enzymology and crystallography, we show that the mucin-degrader R. gnavus ATCC 29149 strain produces an intramolecular trans-sialidase (IT-sialidase) that cleaves off terminal α2-3-linked sialic acid from glycoproteins, releasing 2,7-anhydro-Neu5Ac instead of sialic acid. Evidence of IT-sialidases in human metagenomes indicates that this enzyme occurs in healthy subjects but is more prevalent in IBD metagenomes. Our results uncover a previously unrecognized enzymatic activity in the gut microbiota, which may contribute to the adaptation of intestinal bacteria to the mucosal environment in health and disease.

Metagenomic insights into the human gut resistome and the forces that shape it.

Science.gov (United States)

Forslund, Kristoffer; Sunagawa, Shinichi; Coelho, Luis P; Bork, Peer

2014-03-01

We show how metagenomic analysis of the human gut antibiotic resistome, compared across large populations and against environmental or agricultural resistomes, suggests a strong anthropogenic cause behind increasing antibiotic resistance in bacteria. This area has been the subject of intense and polarized debate driven by economic and political concerns; therefore such recently available insights address an important need. We derive and compare antibiotic resistomes of human gut microbes from 832 individuals from ten different countries. We observe and describe significant differences between samples from these countries in the gut resistance potential, in line with expectations from antibiotic usage and exposure in medical and food production contexts. Our results imply roles for both of these sources in increased resistance among pathogens in recent history. In contrast, other available metadata such as age, body mass index, sex, or health status have little effect on the antibiotic resistance potential of human gut microbes. Also watch the Video Abstract. © 2014 WILEY Periodicals, Inc.

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.

Time for food: The impact of diet on gut microbiota and human health.

Science.gov (United States)

Zhang, Na; Ju, Zhongjie; Zuo, Tao

There is growing recognition of the role of diet on modulating the composition and metabolic activity of the human gut microbiota, which in turn influence health. Dietary ingredients and food additives have a substantial impact on the gut microbiota and hence affect human health. Updates on current understanding of the gut microbiota in diseases and metabolic disorders are addressed in this review, providing insights into how this can be transferred from bench to bench side as gut microbes are integrated with food. The potency of microbiota-targeted biomarkers as a state-of-art tool for diagnosis of diseases was also discussed, and it would instruct individuals with healthy dietary consumption. Herein, recent advances in understanding the effect of diet on gut microbiota from an ecological perspective, and how these insights might promote health by guiding development of prebiotic and probiotic strategies and functional foods, were explored. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Structure of a membrane-attack complex/perforin (MACPF) family protein from the human gut symbiont Bacteroides thetaiotaomicron

International Nuclear Information System (INIS)

Xu, Qingping; Abdubek, Polat; Astakhova, Tamara; Axelrod, Herbert L.; Bakolitsa, Constantina; Cai, Xiaohui; Carlton, Dennis; Chen, Connie; Chiu, Hsiu-Ju; Clayton, Thomas; Das, Debanu; Deller, Marc C.; Duan, Lian; Ellrott, Kyle; Farr, Carol L.; Feuerhelm, Julie; Grant, Joanna C.; Grzechnik, Anna; Han, Gye Won; Jaroszewski, Lukasz; Jin, Kevin K.; Klock, Heath E.; Knuth, Mark W.; Kozbial, Piotr; Krishna, S. Sri; Kumar, Abhinav; Lam, Winnie W.; Marciano, David; Miller, Mitchell D.; Morse, Andrew T.; Nigoghossian, Edward; Nopakun, Amanda; Okach, Linda; Puckett, Christina; Reyes, Ron; Tien, Henry J.; Trame, Christine B.; Bedem, Henry van den; Weekes, Dana; Wooten, Tiffany; Yeh, Andrew; Zhou, Jiadong; Hodgson, Keith O.; Wooley, John; Elsliger, Marc-André; Deacon, Ashley M.; Godzik, Adam; Lesley, Scott A.; Wilson, Ian A.

2010-01-01

The crystal structure of a novel MACPF protein, which may play a role in the adaptation of commensal bacteria to host environments in the human gut, was determined and analyzed. Membrane-attack complex/perforin (MACPF) proteins are transmembrane pore-forming proteins that are important in both human immunity and the virulence of pathogens. Bacterial MACPFs are found in diverse bacterial species, including most human gut-associated Bacteroides species. The crystal structure of a bacterial MACPF-domain-containing protein BT-3439 (Bth-MACPF) from B. thetaiotaomicron, a predominant member of the mammalian intestinal microbiota, has been determined. Bth-MACPF contains a membrane-attack complex/perforin (MACPF) domain and two novel C-terminal domains that resemble ribonuclease H and interleukin 8, respectively. The entire protein adopts a flat crescent shape, characteristic of other MACPF proteins, that may be important for oligomerization. This Bth-MACPF structure provides new features and insights not observed in two previous MACPF structures. Genomic context analysis infers that Bth-MACPF may be involved in a novel protein-transport or nutrient-uptake system, suggesting an important role for these MACPF proteins, which were likely to have been inherited from eukaryotes via horizontal gene transfer, in the adaptation of commensal bacteria to the host environment

Antioxidants keep the potentially probiotic but highly oxygen-sensitive human gut bacterium Faecalibacterium prausnitzii alive at ambient air.

Directory of Open Access Journals (Sweden)

M Tanweer Khan

Full Text Available The beneficial human gut microbe Faecalibacterium prausnitzii is a 'probiotic of the future' since it produces high amounts of butyrate and anti-inflammatory compounds. However, this bacterium is highly oxygen-senstive, making it notoriously difficult to cultivate and preserve. This has so far precluded its clinical application in the treatment of patients with inflammatory bowel diseases. The present studies were therefore aimed at developing a strategy to keep F. prausnitzii alive at ambient air. Our previous research showed that F. prausnitzii can survive in moderately oxygenized environments like the gut mucosa by transfer of electrons to oxygen. For this purpose, the bacterium exploits extracellular antioxidants, such as riboflavin and cysteine, that are abundantly present in the gut. We therefore tested to what extent these antioxidants can sustain the viability of F. prausnitzii at ambient air. The present results show that cysteine can facilitate the survival of F. prausnitzii upon exposure to air, and that this effect is significantly enhanced the by addition of riboflavin and the cryoprotectant inulin. The highly oxygen-sensitive gut bacterium F. prausnitzii can be kept alive at ambient air for 24 h when formulated with the antioxidants cysteine and riboflavin plus the cryoprotectant inulin. Improved formulations were obtained by addition of the bulking agents corn starch and wheat bran. Our present findings pave the way towards the biomedical exploitation of F. prausnitzii in redox-based therapeutics for treatment of dysbiosis-related inflammatory disorders of the human gut.

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...

A systems biology approach to predict and characterize human gut microbial metabolites in colorectal cancer.

Science.gov (United States)

Wang, QuanQiu; Li, Li; Xu, Rong

2018-04-18

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths. It is estimated that about half the cases of CRC occurring today are preventable. Recent studies showed that human gut microbiota and their collective metabolic outputs play important roles in CRC. However, the mechanisms by which human gut microbial metabolites interact with host genetics in contributing CRC remain largely unknown. We hypothesize that computational approaches that integrate and analyze vast amounts of publicly available biomedical data have great potential in better understanding how human gut microbial metabolites are mechanistically involved in CRC. Leveraging vast amount of publicly available data, we developed a computational algorithm to predict human gut microbial metabolites for CRC. We validated the prediction algorithm by showing that previously known CRC-associated gut microbial metabolites ranked highly (mean ranking: top 10.52%; median ranking: 6.29%; p-value: 3.85E-16). Moreover, we identified new gut microbial metabolites likely associated with CRC. Through computational analysis, we propose potential roles for tartaric acid, the top one ranked metabolite, in CRC etiology. In summary, our data-driven computation-based study generated a large amount of associations that could serve as a starting point for further experiments to refute or validate these microbial metabolite associations in CRC cancer.

Human mini-guts: new insights into intestinal physiology and host-pathogen interactions.

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In, Julie G; Foulke-Abel, Jennifer; Estes, Mary K; Zachos, Nicholas C; Kovbasnjuk, Olga; Donowitz, Mark

2016-11-01

The development of indefinitely propagating human 'mini-guts' has led to a rapid advance in gastrointestinal research related to transport physiology, developmental biology, pharmacology, and pathophysiology. These mini-guts, also called enteroids or colonoids, are derived from LGR5 + intestinal stem cells isolated from the small intestine or colon. Addition of WNT3A and other growth factors promotes stemness and results in viable, physiologically functional human intestinal or colonic cultures that develop a crypt-villus axis and can be differentiated into all intestinal epithelial cell types. The success of research using human enteroids has highlighted the limitations of using animals or in vitro, cancer-derived cell lines to model transport physiology and pathophysiology. For example, curative or preventive therapies for acute enteric infections have been limited, mostly due to the lack of a physiological human intestinal model. However, the human enteroid model enables specific functional studies of secretion and absorption in each intestinal segment as well as observations of the earliest molecular events that occur during enteric infections. This Review describes studies characterizing these human mini-guts as a physiological model to investigate intestinal transport and host-pathogen interactions.

Gut Microbiota in Human Systemic Lupus Erythematosus and a Mouse Model of Lupus.

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Luo, Xin M; Edwards, Michael R; Mu, Qinghui; Yu, Yang; Vieson, Miranda D; Reilly, Christopher M; Ahmed, S Ansar; Bankole, Adegbenga A

2018-02-15

Gut microbiota dysbiosis has been observed in a number of autoimmune diseases. However, the role of the gut microbiota in systemic lupus erythematosus (SLE), a prototypical autoimmune disease characterized by persistent inflammation in multiple organs of the body, remains elusive. Here we report the dynamics of the gut microbiota in a murine lupus model, NZB/W F1, as well as intestinal dysbiosis in a small group of SLE patients with active disease. The composition of the gut microbiota changed markedly before and after the onset of lupus disease in NZB/W F1 mice, with greater diversity and increased representation of several bacterial species as lupus progressed from the predisease stage to the diseased stage. However, we did not control for age and the cage effect. Using dexamethasone as an intervention to treat SLE-like signs, we also found that a greater abundance of a group of lactobacilli (for which a species assignment could not be made) in the gut microbiota might be correlated with more severe disease in NZB/W F1 mice. Results of the human study suggest that, compared to control subjects without immune-mediated diseases, SLE patients with active lupus disease possessed an altered gut microbiota that differed in several particular bacterial species (within the genera Odoribacter and Blautia and an unnamed genus in the family Rikenellaceae ) and was less diverse, with increased representation of Gram-negative bacteria. The Firmicutes / Bacteroidetes ratios did not differ between the SLE microbiota and the non-SLE microbiota in our human cohort. IMPORTANCE SLE is a complex autoimmune disease with no known cure. Dysbiosis of the gut microbiota has been reported for both mice and humans with SLE. In this emerging field, however, more studies are required to delineate the roles of the gut microbiota in different lupus-prone mouse models and people with diverse manifestations of SLE. Here, we report changes in the gut microbiota in NZB/W F1 lupus-prone mice and a

MetaPro-IQ: a universal metaproteomic approach to studying human and mouse gut microbiota.

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Zhang, Xu; Ning, Zhibin; Mayne, Janice; Moore, Jasmine I; Li, Jennifer; Butcher, James; Deeke, Shelley Ann; Chen, Rui; Chiang, Cheng-Kang; Wen, Ming; Mack, David; Stintzi, Alain; Figeys, Daniel

2016-06-24

The gut microbiota has been shown to be closely associated with human health and disease. While next-generation sequencing can be readily used to profile the microbiota taxonomy and metabolic potential, metaproteomics is better suited for deciphering microbial biological activities. However, the application of gut metaproteomics has largely been limited due to the low efficiency of protein identification. Thus, a high-performance and easy-to-implement gut metaproteomic approach is required. In this study, we developed a high-performance and universal workflow for gut metaproteome identification and quantification (named MetaPro-IQ) by using the close-to-complete human or mouse gut microbial gene catalog as database and an iterative database search strategy. An average of 38 and 33 % of the acquired tandem mass spectrometry (MS) spectra was confidently identified for the studied mouse stool and human mucosal-luminal interface samples, respectively. In total, we accurately quantified 30,749 protein groups for the mouse metaproteome and 19,011 protein groups for the human metaproteome. Moreover, the MetaPro-IQ approach enabled comparable identifications with the matched metagenome database search strategy that is widely used but needs prior metagenomic sequencing. The response of gut microbiota to high-fat diet in mice was then assessed, which showed distinct metaproteome patterns for high-fat-fed mice and identified 849 proteins as significant responders to high-fat feeding in comparison to low-fat feeding. We present MetaPro-IQ, a metaproteomic approach for highly efficient intestinal microbial protein identification and quantification, which functions as a universal workflow for metaproteomic studies, and will thus facilitate the application of metaproteomics for better understanding the functions of gut microbiota in health and disease.

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.

Ancient acquisition of "alginate utilization loci" by human gut microbiota.

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Mathieu, Sophie; Touvrey-Loiodice, Mélanie; Poulet, Laurent; Drouillard, Sophie; Vincentelli, Renaud; Henrissat, Bernard; Skjåk-Bræk, Gudmund; Helbert, William

2018-05-23

In bacteria from the phylum Bacteroidetes, the genes coding for enzymes involved in polysaccharide degradation are often colocalized and coregulated in so-called "polysaccharide utilization loci" (PULs). PULs dedicated to the degradation of marine polysaccharides (e.g. laminaran, ulvan, alginate and porphyran) have been characterized in marine bacteria. Interestingly, the gut microbiome of Japanese individuals acquired, by lateral transfer from marine bacteria, the genes involved in the breakdown of porphyran, the cell wall polysaccharide of the red seaweed used in maki. Sequence similarity analyses predict that the human gut microbiome also encodes enzymes for the degradation of alginate, the main cell wall polysaccharide of brown algae. We undertook the functional characterization of diverse polysaccharide lyases from family PL17, frequently found in marine bacteria as well as those of human gut bacteria. We demonstrate here that this family is polyspecific. Our phylogenetic analysis of family PL17 reveals that all alginate lyases, which have all the same specificity and mode of action, cluster together in a very distinct subfamily. The alginate lyases found in human gut bacteria group together in a single clade which is rooted deeply in the PL17 tree. These enzymes were found in PULs containing PL6 enzymes, which also clustered together in the phylogenetic tree of PL6. Together, biochemical and bioinformatics analyses suggest that acquisition of this system appears ancient and, because only traces of two successful transfers were detected upon inspection of PL6 and PL17 families, the pace of acquisition of marine polysaccharide degradation system is probably very slow.

Characterization of the human DNA gut virome across populations with different subsistence strategies and geographical origin.

Science.gov (United States)

Rampelli, Simone; Turroni, Silvia; Schnorr, Stephanie L; Soverini, Matteo; Quercia, Sara; Barone, Monica; Castagnetti, Andrea; Biagi, Elena; Gallinella, Giorgio; Brigidi, Patrizia; Candela, Marco

2017-11-01

It is a matter of fact that the human gut microbiome also includes a non-bacterial fraction represented by eukaryotic cells and viruses. To further explore the gut microbiome variation in human populations, here we characterized the human DNA viral community from publicly available gut metagenome data sets from human populations with different geographical origin and lifestyle. In particular, such data sets encompass microbiome information from two western urban societies (USA and Italy), as well as two traditional hunter-gatherer communities (the Hadza from Tanzania and Matses from Peru) and one pre-agricultural tribe (Tunapuco from Peru). Our results allowed for the first taxonomic reconstruction of the complex viral metacommunities within the human gut. The core virome structure included herpesviruses, papillomaviruses, polyomaviruses, adenoviruses and anelloviruses. Using Random Forests and a co-occurrence analysis approach, we identified the viruses that distinguished populations according to their geographical origin and/or lifestyle. This paves the way for new research aimed at investigating the biological role of the gut virome in human physiology, and the importance of our viral counterpart in the microbiome-host co-evolutionary process. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

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...

A wide diversity of bacteria from the human gut produces and degrades biogenic amines.

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Pugin, Benoit; Barcik, Weronika; Westermann, Patrick; Heider, Anja; Wawrzyniak, Marcin; Hellings, Peter; Akdis, Cezmi A; O'Mahony, Liam

2017-01-01

Background : Biogenic amines (BAs) are metabolites produced by the decarboxylation of amino acids with significant physiological functions in eukaryotic and prokaryotic cells. BAs can be produced by bacteria in fermented foods, but little is known concerning the potential for microbes within the human gut microbiota to produce or degrade BAs. Objective : To isolate and identify BA-producing and BA-degrading microbes from the human gastrointestinal tract. Design : Fecal samples from human volunteers were screened on multiple growth media, under multiple growth conditions. Bacterial species were identified using 16S rRNA sequencing and BA production or degradation was assessed using ultra-performance liquid chromatography. Results : In total, 74 BA-producing or BA-degrading strains were isolated from the human gut. These isolates belong to the genera Bifidobacterium , Clostridium , Enterococcus , Lactobacillus , Pediococcus , Streptococcus , Enterobacter , Escherichia , Klebsiella , Morganella and Proteus . While differences in production or degradation of specific BAs were observed at the strain level, our results suggest that these metabolic activities are widely spread across different taxa present within the human gut microbiota. Conclusions : The isolation and identification of microbes from the human gut with BA-producing and BA-degrading metabolic activity is an important first step in developing a better understanding of how these metabolites influence health and disease.

Modulation of the human gut microbiota by dietary fibres occurs at the species level.

Science.gov (United States)

Chung, Wing Sun Faith; Walker, Alan W; Louis, Petra; Parkhill, Julian; Vermeiren, Joan; Bosscher, Douwina; Duncan, Sylvia H; Flint, Harry J

2016-01-11

. Furthermore, the gut environment, especially pH, plays a key role in determining the outcome of interspecies competition. This makes it crucial to put greater effort into identifying the range of bacteria that may be stimulated by a given prebiotic approach. Both for reasons of efficacy and of safety, the development of prebiotics intended to benefit human health has to take account of the highly individual species profiles that may result.

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.

The role of gut microbiota in human obesity: recent findings and future perspectives.

Science.gov (United States)

Tagliabue, A; Elli, M

2013-03-01

In recent years, gut microbiota have gained a growing interest as an environmental factor that may affect the predisposition toward adiposity. In this review, we describe and discuss the research that has focused on the involvement of gut microbiota in human obesity. We also summarize the current knowledge concerning the health effects of the composition of gut microbiota, acquired using the most recent methodological approaches, and the potential influence of gut microbiota on adiposity, as revealed by animal studies. Original research studies that were published in English or French until December 2011 were selected through a computer-assisted literature search. The studies conducted to date show that there are differences in the gut microbiota between obese and normal-weight experimental animals. There is also evidence that a high-fat diet may induce changes in gut microbiota in animal models regardless of the presence of obesity. In humans, obesity has been associated with reduced bacterial diversity and an altered representation of bacterial species, but the identified differences are not homogeneous among the studies. The question remains as to whether changes in the intestinal microbial community are one of the environmental causes of overweight and obesity or if they are a consequence of obesity, specifically of the unbalanced diet that often accompanies the development of excess weight gain. In the future, larger studies on the potential role of intestinal microbiota in human obesity should be conducted at the species level using standardized analytical techniques and taking all of the possible confounding variables into account. Copyright © 2012 Elsevier B.V. All rights reserved.

Communities of microbial eukaryotes in the mammalian gut within the context of environmental eukaryotic diversity

Energy Technology Data Exchange (ETDEWEB)

Parfrey, Laura Wegener; Walters, William A.; Lauber, Christian L.; Clemente, Jose C.; Berg-Lyons, Donna; Teiling, Clotilde; Kodira, Chinnappa; Mohiuddin, Mohammed; Brunelle, Julie; Driscoll, Mark; Fierer, Noah; Gilbert, Jack A.; Knight, Rob

2014-06-19

Eukaryotic microbes (protists) residing in the vertebrate gut influence host health and disease, but their diversity and distribution in healthy hosts is poorly understood. Protists found in the gut are typically considered parasites, but many are commensal and some are beneficial. Further, the hygiene hypothesis predicts that association with our co-evolved microbial symbionts may be important to overall health. It is therefore imperative that we understand the normal diversity of our eukaryotic gut microbiota to test for such effects and avoid eliminating commensal organisms. We assembled a dataset of healthy individuals from two populations, one with traditional, agrarian lifestyles and a second with modern, westernized lifestyles, and characterized the human eukaryotic microbiota via high-throughput sequencing. To place the human gut microbiota within a broader context our dataset also includes gut samples from diverse mammals and samples from other aquatic and terrestrial environments. We curated the SILVA ribosomal database to reflect current knowledge of eukaryotic taxonomy and employ it as a phylogenetic framework to compare eukaryotic diversity across environment. We show that adults from the non-western population harbor a diverse community of protists, and diversity in the human gut is comparable to that in other mammals. However, the eukaryotic microbiota of the western population appears depauperate. The distribution of symbionts found in mammals reflects both host phylogeny and diet. Eukaryotic microbiota in the gut are less diverse and more patchily distributed than bacteria. More broadly, we show that eukaryotic communities in the gut are less diverse than in aquatic and terrestrial habitats, and few taxa are shared across habitat types, and diversity patterns of eukaryotes are correlated with those observed for bacteria. These results outline the distribution and diversity of microbial eukaryotic communities in the mammalian gut and across

Role of intestinal microbiota and metabolites on gut homeostasis and human diseases.

Science.gov (United States)

Lin, Lan; Zhang, Jianqiong

2017-01-06

A vast diversity of microbes colonizes in the human gastrointestinal tract, referred to intestinal microbiota. Microbiota and products thereof are indispensable for shaping the development and function of host innate immune system, thereby exerting multifaceted impacts in gut health. This paper reviews the effects on immunity of gut microbe-derived nucleic acids, and gut microbial metabolites, as well as the involvement of commensals in the gut homeostasis. We focus on the recent findings with an intention to illuminate the mechanisms by which the microbiota and products thereof are interacting with host immunity, as well as to scrutinize imbalanced gut microbiota (dysbiosis) which lead to autoimmune disorders including inflammatory bowel disease (IBD), Type 1 diabetes (T1D) and systemic immune syndromes such as rheumatoid arthritis (RA). In addition to their well-recognized benefits in the gut such as occupation of ecological niches and competition with pathogens, commensal bacteria have been shown to strengthen the gut barrier and to exert immunomodulatory actions within the gut and beyond. It has been realized that impaired intestinal microbiota not only contribute to gut diseases but also are inextricably linked to metabolic disorders and even brain dysfunction. A better understanding of the mutual interactions of the microbiota and host immune system, would shed light on our endeavors of disease prevention and broaden the path to our discovery of immune intervention targets for disease treatment.

Gut microbiota and obesity.

Science.gov (United States)

Gérard, Philippe

2016-01-01

The human intestine harbors a complex bacterial community called the gut microbiota. This microbiota is specific to each individual despite the existence of several bacterial species shared by the majority of adults. The influence of the gut microbiota in human health and disease has been revealed in the recent years. Particularly, the use of germ-free animals and microbiota transplant showed that the gut microbiota may play a causal role in the development of obesity and associated metabolic disorders, and lead to identification of several mechanisms. In humans, differences in microbiota composition, functional genes and metabolic activities are observed between obese and lean individuals suggesting a contribution of the gut microbiota to these phenotypes. Finally, the evidence linking gut bacteria to host metabolism could allow the development of new therapeutic strategies based on gut microbiota modulation to treat or prevent obesity.

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

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.

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

Complete Genome Sequence of the Human Gut Symbiont Roseburia hominis

DEFF Research Database (Denmark)

Travis, Anthony J.; Kelly, Denise; Flint, Harry J

2015-01-01

We report here the complete genome sequence of the human gut symbiont Roseburia hominis A2-183(T) (= DSM 16839(T) = NCIMB 14029(T)), isolated from human feces. The genome is represented by a 3,592,125-bp chromosome with 3,405 coding sequences. A number of potential functions contributing to host...

Influence of food consumption patterns and Galician lifestyle on human gut microbiota.

Science.gov (United States)

Castro-Penalonga, María; Roca-Saavedra, Paula; Miranda, Jose Manuel; Porto-Arias, Jose Julio; Nebot, Carolina; Cardelle-Cobas, Alejandra; Franco, Carlos Manuel; Cepeda, Alberto

2018-02-01

The proportion of different microbial populations in the human gut is an important factor that in recent years has been linked to obesity and numerous metabolic diseases. Because there are many factors that can affect the composition of human gut microbiota, it is of interest to have information about what is the composition of the gut microbiota in different populations in order to better understand the possibilities for improving nutritional management. A group of 31 volunteers were selected according to established inclusion and exclusion criteria and were asked about their diet history, lifestyle patterns, and adherence to the Southern European Atlantic Diet. Fecal samples were taken and subsequently analyzed by real-time PCR. The results indicated different dietary patterns for subjects who consumed a higher amount of fruits, vegetables, legumes, and fish and a lower amount of bakery foods and precooked foods and snacks compared to Spanish consumption data. Most participants showed intermediate or high adherence to Southern European Atlantic Diet, and an analysis of gut microbiota showed high numbers of total bacteria and Actinobacteria, as well as high amounts of bacteria belonging to the genera Lactobacillus spp. and Bifidobacterium spp. A subsequent statistical comparison also revealed differences in gut microbiota depending on the subject's body weight, age, or degree of adherence to the Southern European Atlantic Diet.

"Omic" investigations of protozoa and worms for a deeper understanding of the human gut "parasitome".

Science.gov (United States)

Marzano, Valeria; Mancinelli, Livia; Bracaglia, Giorgia; Del Chierico, Federica; Vernocchi, Pamela; Di Girolamo, Francesco; Garrone, Stefano; Tchidjou Kuekou, Hyppolite; D'Argenio, Patrizia; Dallapiccola, Bruno; Urbani, Andrea; Putignani, Lorenza

2017-11-01

The human gut has been continuously exposed to a broad spectrum of intestinal organisms, including viruses, bacteria, fungi, and parasites (protozoa and worms), over millions of years of coevolution, and plays a central role in human health. The modern lifestyles of Western countries, such as the adoption of highly hygienic habits, the extensive use of antimicrobial drugs, and increasing globalisation, have dramatically altered the composition of the gut milieu, especially in terms of its eukaryotic "citizens." In the past few decades, numerous studies have highlighted the composition and role of human intestinal bacteria in physiological and pathological conditions, while few investigations exist on gut parasites and particularly on their coexistence and interaction with the intestinal microbiota. Studies of the gut "parasitome" through "omic" technologies, such as (meta)genomics, transcriptomics, proteomics, and metabolomics, are herein reviewed to better understand their role in the relationships between intestinal parasites, host, and resident prokaryotes, whether pathogens or commensals. Systems biology-based profiles of the gut "parasitome" under physiological and severe disease conditions can indeed contribute to the control of infectious diseases and offer a new perspective of omics-assisted tropical medicine.

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.

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

Colonic transit time is related to bacterial metabolism and mucosal turnover in the human gut

DEFF Research Database (Denmark)

Roager, Henrik Munch; Hansen, Lea Benedicte Skov; Bahl, Martin Iain

Little is known about how colonic transit time relates to human colonic metabolism, and its importance for host health, although stool consistency, a proxy for colonic transit time, has recently been negatively associated with gut microbial richness. To address the relationships between colonic t...... imply a healthy gut microbial ecosystem and points at colonic transit time as a highly important factor to consider in microbiome and metabolomics studies.......Little is known about how colonic transit time relates to human colonic metabolism, and its importance for host health, although stool consistency, a proxy for colonic transit time, has recently been negatively associated with gut microbial richness. To address the relationships between colonic...... transit time and the gut microbial composition and metabolism, we assessed the colonic transit time of 98 subjects using radiopaque markers, and profiled their gut microbiota by16S rRNA gene sequencing and their urine metabolome by ultra performance liquid chromatography mass spectrometry. Based...

Differential effects of antibiotic therapy on the structure and function of human gut microbiota.

Directory of Open Access Journals (Sweden)

Ana Elena Pérez-Cobas

Full Text Available The human intestinal microbiota performs many essential functions for the host. Antimicrobial agents, such as antibiotics (AB, are also known to disturb microbial community equilibrium, thereby having an impact on human physiology. While an increasing number of studies investigate the effects of AB usage on changes in human gut microbiota biodiversity, its functional effects are still poorly understood. We performed a follow-up study to explore the effect of ABs with different modes of action on human gut microbiota composition and function. Four individuals were treated with different antibiotics and samples were taken before, during and after the AB course for all of them. Changes in the total and in the active (growing microbiota as well as the functional changes were addressed by 16S rRNA gene and metagenomic 454-based pyrosequencing approaches. We have found that the class of antibiotic, particularly its antimicrobial effect and mode of action, played an important role in modulating the gut microbiota composition and function. Furthermore, analysis of the resistome suggested that oscillatory dynamics are not only due to antibiotic-target resistance, but also to fluctuations in the surviving bacterial community. Our results indicated that the effect of AB on the human gut microbiota relates to the interaction of several factors, principally the properties of the antimicrobial agent, and the structure, functions and resistance genes of the microbial community.

ResistoMap-online visualization of human gut microbiota antibiotic resistome.

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Yarygin, Konstantin S; Kovarsky, Boris A; Bibikova, Tatyana S; Melnikov, Damir S; Tyakht, Alexander V; Alexeev, Dmitry G

2017-07-15

We created ResistoMap—a Web-based interactive visualization of the presence of genetic determinants conferring resistance to antibiotics, biocides and heavy metals in human gut microbiota. ResistoMap displays the data on more than 1500 published gut metagenomes of world populations including both healthy subjects and patients. Multiparameter display filters allow visual assessment of the associations between the meta-data and proportions of resistome. The geographic map navigation layer allows to state hypotheses regarding the global trends of antibiotic resistance and correlates the gut resistome variations with the national clinical guidelines on antibiotics application. ResistoMap was implemented using AngularJS, CoffeeScript, D3.js and TopoJSON. The tool is publicly available at http://resistomap.rcpcm.org. yarygin@phystech.edu. Supplementary data are available at Bioinformatics online. © The Author(s) 2017. Published by Oxford University Press.

Characterization and detection of a widely distributed gene cluster that predicts anaerobic choline utilization by human gut bacteria.

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Martínez-del Campo, Ana; Bodea, Smaranda; Hamer, Hilary A; Marks, Jonathan A; Haiser, Henry J; Turnbaugh, Peter J; Balskus, Emily P

2015-04-14

Elucidation of the molecular mechanisms underlying the human gut microbiota's effects on health and disease has been complicated by difficulties in linking metabolic functions associated with the gut community as a whole to individual microorganisms and activities. Anaerobic microbial choline metabolism, a disease-associated metabolic pathway, exemplifies this challenge, as the specific human gut microorganisms responsible for this transformation have not yet been clearly identified. In this study, we established the link between a bacterial gene cluster, the choline utilization (cut) cluster, and anaerobic choline metabolism in human gut isolates by combining transcriptional, biochemical, bioinformatic, and cultivation-based approaches. Quantitative reverse transcription-PCR analysis and in vitro biochemical characterization of two cut gene products linked the entire cluster to growth on choline and supported a model for this pathway. Analyses of sequenced bacterial genomes revealed that the cut cluster is present in many human gut bacteria, is predictive of choline utilization in sequenced isolates, and is widely but discontinuously distributed across multiple bacterial phyla. Given that bacterial phylogeny is a poor marker for choline utilization, we were prompted to develop a degenerate PCR-based method for detecting the key functional gene choline TMA-lyase (cutC) in genomic and metagenomic DNA. Using this tool, we found that new choline-metabolizing gut isolates universally possessed cutC. We also demonstrated that this gene is widespread in stool metagenomic data sets. Overall, this work represents a crucial step toward understanding anaerobic choline metabolism in the human gut microbiota and underscores the importance of examining this microbial community from a function-oriented perspective. Anaerobic choline utilization is a bacterial metabolic activity that occurs in the human gut and is linked to multiple diseases. While bacterial genes responsible for

Feeding the microbiota-gut-brain axis: diet, microbiome, and neuropsychiatry.

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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.

Estrogen decreases tight junction protein ZO-1 expression in human primary gut tissues.

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Zhou, Zejun; Zhang, Lumin; Ding, Miao; Luo, Zhenwu; Yuan, Shao; Bansal, Meena B; Gilkeson, Gary; Lang, Ren; Jiang, Wei

2017-10-01

Females have a higher prevalence of most autoimmune diseases; however, the mechanism is unknown. In this study, we examined the expression of tight junction protein zonula occludens 1 (ZO-1) and estrogen receptor (ER)-α/β in human primary gut tissues by immunohistochemistry, immunofluorescence and qPCR. The expression of ZO-1 and ER-β but not ER-α was present in both male and female gut tissues. There was no sex difference in ER-β expression, but ZO-1 expression was decreased in females compared to males. In vitro, estrogen treatment decreased ZO-1 mRNA and protein expression, ZO-1 promoter activity, IL-6 production, and NF-κB activation in human primary gut tissues or the Caco-2 cells, but increased the ER-β expression in Caco-2 cells. Consistently, plasma IL-6 levels in females were reduced relative to males in vivo. Our finding indicates that estrogen may play a role in gut tight junction expression and permeability. Copyright © 2017 Elsevier Inc. All rights reserved.

Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism

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The architecture of the human distal gut microbiota (microbiota) is sculpted by the complex carbohydrates delivered in the diet. Yeasts, which are among the earliest domesticated microorganisms and have been a component of the human diet for at least 7000 years, possess an elaborate cell wall alpha-...

Transcriptional interactions suggest niche segregation among microorganisms in the human gut

DEFF Research Database (Denmark)

Plichta, Damian Rafal; Juncker, Agnieszka; dos Santos, Marcelo Bertalan Quintanilha

2016-01-01

The human gastrointestinal (GI) tract is the habitat for hundreds of microbial species, of which many cannot be cultivated readily, presumably because of the dependencies between species 1. Studies of microbial co-occurrence in the gut have indicated community substructures that may reflect...... functional and metabolic interactions between cohabiting species 2,3. To move beyond species co-occurrence networks, we systematically identified transcriptional interactions between pairs of coexisting gut microbes using metagenomics and microarray-based metatranscriptomics data from 233 stool samples from...

The chemical interactome space between the human host and the genetically defined gut metabotypes

DEFF Research Database (Denmark)

Jacobsen, Ulrik Plesner; Nielsen, Henrik Bjørn; Hildebrand, Falk

2013-01-01

symbiosis in the gut of mammals, mechanistic understanding of the contributions of the gut microbiome and how variations in the metabotypes are linked to the host health are obscure. Here, we mapped the entire metabolic potential of the gut microiome based solely on metagenomics sequencing data derived from...... pharmacy in our guts. Furthermore, we established connections between the systemic effects of non-antibiotic drugs and the gut microbiome of relevance to drug side effects and health-care solutions.......The bacteria that colonize the gastrointestinal tracts of mammals represent a highly selected microbiome that has a profound influence on human physiology by shaping the host’s metabolic and immune system activity. Despite the recent advances on the biological principles that underlie microbial...

Kiwifruit, mucins, and the gut barrier.

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Moughan, Paul J; Rutherfurd, Shane M; Balan, Prabhu

2013-01-01

Kiwifruit has long been regarded in China, where it originated from, for its health properties and particularly in relation to digestion and general gut health. There are a number of physical and chemical properties of the fruit, including its dietary fiber content, the presence of raphides, its high water holding capacity and actinidin content, that suggest that kiwifruit may be effective in influencing gut mucin production and thus enhancing the integrity of the gut barrier. The mucous layer, which comprises mucins and other materials, overlying the mucosal epithelium, is an important component of the gut barrier. The gut barrier plays a crucial role in separating the host from the often noxious external environment. The mucous layer, which covers the entire gastrointestinal tract (GIT), is the front line of innate host defense. There have been few direct studies of the effect of kiwifruit ingestion on mucin production in the GIT, and findings that are available using animal models are somewhat inconsistent. Taking results for digesta mucin content, number of goblet cells, and mucin gene expression, together, it would seem that green kiwifruit and possibly gold kiwifruit do influence gut mucin production, and the kiwifruit as part of a balanced diet may help to maintain the mucous layer and gut barrier. More corroborative experimental evidence is needed, and studies need to be undertaken in humans. Copyright © 2013 Elsevier Inc. All rights reserved.

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

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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.

The Gut Microbiota in Host Metabolism and Pathogen Challenges

DEFF Research Database (Denmark)

Holm, Jacob Bak

The human microbiota consists of a complex community of microbial cells that live on and inside each person in a close relationship with their host. The majority of the microbial cells are harboured by the gastro intestinal tract where 10-100 trillion bacteria reside. The microbiota is a dynamic...... community where both composition and function can be affected by changes in the local environment. With the microbiota containing ~150 times more genes than the human host, the microbiota provides a large modifiable “secondary genome” (metagenome). Within the last decade, changes in the gut microbiota...... composition has indeed been established as a factor contributing to the health of the host. Therefore, being able to understand, control and modify the gut microbiota is a promising way of improving health. The following thesis is based on four different projects investigating the murine gut microbiota...

The Human Gut Phage Community and Its Implications for Health and Disease.

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Manrique, Pilar; Dills, Michael; Young, Mark J

2017-06-08

In this review, we assess our current understanding of the role of bacteriophages infecting the human gut bacterial community in health and disease. In general, bacteriophages contribute to the structure of their microbial communities by driving host and viral diversification, bacterial evolution, and by expanding the functional diversity of ecosystems. Gut bacteriophages are an ensemble of unique and shared phages in individuals, which encompass temperate phages found predominately as prophage in gut bacteria (prophage reservoir) and lytic phages. In healthy individuals, only a small fraction of the prophage reservoir is activated and found as extracellular phages. Phage community dysbiosis is characterized by a shift in the activated prophage community or an increase of lytic phages, and has been correlated with disease, suggesting that a proper balance between lysis and lysogeny is needed to maintain health. Consequently, the concept of microbial dysbiosis might be extended to the phage component of the microbiome as well. Understanding the dynamics and mechanisms to restore balance after dysbiosis is an active area of research. The use of phage transplants to re-establish health suggests that phages can be used as disease treatment. Such advances represent milestones in our understanding of gut phages in human health and should fuel research on their role in health and disease.

Exercise Alters Gut Microbiota Composition and Function in Lean and Obese Humans.

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Allen, Jacob M; Mailing, Lucy J; Niemiro, Grace M; Moore, Rachel; Cook, Marc D; White, Bryan A; Holscher, Hannah D; Woods, Jeffrey A

2018-04-01

Exercise is associated with altered gut microbial composition, but studies have not investigated whether the gut microbiota and associated metabolites are modulated by exercise training in humans. We explored the impact of 6 wk of endurance exercise on the composition, functional capacity, and metabolic output of the gut microbiota in lean and obese adults with multiple-day dietary controls before outcome variable collection. Thirty-two lean (n = 18 [9 female]) and obese (n = 14 [11 female]), previously sedentary subjects participated in 6 wk of supervised, endurance-based exercise training (3 d·wk) that progressed from 30 to 60 min·d and from moderate (60% of HR reserve) to vigorous intensity (75% HR reserve). Subsequently, participants returned to a sedentary lifestyle activity for a 6-wk washout period. Fecal samples were collected before and after 6 wk of exercise, as well as after the sedentary washout period, with 3-d dietary controls in place before each collection. β-diversity analysis revealed that exercise-induced alterations of the gut microbiota were dependent on obesity status. Exercise increased fecal concentrations of short-chain fatty acids in lean, but not obese, participants. Exercise-induced shifts in metabolic output of the microbiota paralleled changes in bacterial genes and taxa capable of short-chain fatty acid production. Lastly, exercise-induced changes in the microbiota were largely reversed once exercise training ceased. These findings suggest that exercise training induces compositional and functional changes in the human gut microbiota that are dependent on obesity status, independent of diet and contingent on the sustainment of exercise.

A role for gut-associated lymphoid tissue in shaping the human B cell repertoire.

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Vossenkämper, Anna; Blair, Paul A; Safinia, Niloufar; Fraser, Louise D; Das, Lisa; Sanders, Theodore J; Stagg, Andrew J; Sanderson, Jeremy D; Taylor, Kirstin; Chang, Fuju; Choong, Lee M; D'Cruz, David P; Macdonald, Thomas T; Lombardi, Giovanna; Spencer, Jo

2013-08-26

We have tracked the fate of immature human B cells at a critical stage in their development when the mature B cell repertoire is shaped. We show that a major subset of bone marrow emigrant immature human B cells, the transitional 2 (T2) B cells, homes to gut-associated lymphoid tissue (GALT) and that most T2 B cells isolated from human GALT are activated. Activation in GALT is a previously unknown potential fate for immature human B cells. The process of maturation from immature transitional B cell through to mature naive B cell includes the removal of autoreactive cells from the developing repertoire, a process which is known to fail in systemic lupus erythematosus (SLE). We observe that immature B cells in SLE are poorly equipped to access the gut and that gut immune compartments are depleted in SLE. Thus, activation of immature B cells in GALT may function as a checkpoint that protects against autoimmunity. In healthy individuals, this pathway may be involved in generating the vast population of IgA plasma cells and also the enigmatic marginal zone B cell subset that is poorly understood in humans.

Effect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism

DEFF Research Database (Denmark)

Mikkelsen, Kristian H; Frost, Morten; Bahl, Martin Iain

2015-01-01

The gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans. Meal tests...... tolerance, insulin secretion or plasma lipid concentrations were found. Apart from an acute and reversible increase in peptide YY secretion, no changes were observed in postprandial gut hormone release. As evaluated by selective cultivation of gut bacteria, a broad-spectrum 4-day antibiotics course...... with vancomycin, gentamycin and meropenem induced shifts in gut microbiota composition that had no clinically relevant short or long-term effects on metabolic variables in healthy glucose-tolerant males. clinicaltrials.gov NCT01633762....

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

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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

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

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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.

How mass spectrometric approaches applied to bacterial identification have revolutionized the study of human gut microbiota.

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Grégory, Dubourg; Chaudet, Hervé; Lagier, Jean-Christophe; Raoult, Didier

2018-03-01

Describing the human hut gut microbiota is one the most exciting challenges of the 21 st century. Currently, high-throughput sequencing methods are considered as the gold standard for this purpose, however, they suffer from several drawbacks, including their inability to detect minority populations. The advent of mass-spectrometric (MS) approaches to identify cultured bacteria in clinical microbiology enabled the creation of the culturomics approach, which aims to establish a comprehensive repertoire of cultured prokaryotes from human specimens using extensive culture conditions. Areas covered: This review first underlines how mass spectrometric approaches have revolutionized clinical microbiology. It then highlights the contribution of MS-based methods to culturomics studies, paying particular attention to the extension of the human gut microbiota repertoire through the discovery of new bacterial species. Expert commentary: MS-based approaches have enabled cultivation methods to be resuscitated to study the human gut microbiota and thus to fill in the blanks left by high-throughput sequencing methods in terms of culturing minority populations. Continued efforts to recover new taxa using culture methods, combined with their rapid implementation in genomic databases, would allow for an exhaustive analysis of the gut microbiota through the use of a comprehensive approach.

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.

Prostaglandin H synthase immunoreactivity in human gut. An immunohistochemical study

DEFF Research Database (Denmark)

Mikkelsen, H B; Rumessen, J J; Qvortrup, Klaus

1991-01-01

Prostaglandins exhibit a variety of actions on intestinal smooth muscle depending upon the type, dose and muscle layer studied. As the cellular origin of prostaglandin H (PGH) synthase has not been established with certainty in the human gut wall, we studied the localization of PGH synthase...

A human gut microbial gene catalogue established by metagenomic sequencing

DEFF Research Database (Denmark)

dos Santos, Marcelo Bertalan Quintanilha; Sicheritz-Pontén, Thomas; Nielsen, Henrik Bjørn

2010-01-01

To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence...

Beyond gut microbiota: understanding obesity and type 2 diabetes.

Science.gov (United States)

Lau, Eva; Carvalho, Davide; Pina-Vaz, Cidália; Barbosa, José-Adelino; Freitas, Paula

2015-01-01

Obesity and type 2 diabetes are metabolic diseases that have reached epidemic proportions worldwide. Although their etiology is complex, both result from interplay between behaviour, environment and genetic factors. Within ambient determinants, human overall gut bacteria have been identified as a crucial mediator of obesity and its consequences. Gut microbiota plays a crucial role in gastro-intestinal mucosa permeability and regulates the fermentation and absorption of dietary polyssacharides, which may explain its importance in the regulation of fat accumulation and the resultant development of obesity-related diseases. The main objective of this review is to address the pathogenic association between gut microbiota and obesity and to explore related innovative therapeutic targets. New insights into the role of the small bowel and gut microbiota in diabetes and obesity may make possible the development of integrated strategies to prevent and treat these metabolic disorders.

Gut bifidobacteria populations in human health and aging

Directory of Open Access Journals (Sweden)

Silvia Arboleya

2016-08-01

Full Text Available The intestinal microbiota has increasingly been shown to have a vital role in various aspects of human health. Indeed, several studies have linked alterations in the gut microbiota with the development of different diseases. Among the vast gut bacterial community, Bifidobacterium is a genus which dominates the intestine of healthy breast-fed infants whereas in adulthood the levels are lower but relatively stable. The presence of different species of bifidobacteria changes with age, from the childhood to old age. Bifidobacterium longum, Bifidobacterium breve and Bifidobacterium bifidum are generally dominant in infants whereas Bifidobacterium catenulatum, Bifidobacterium adolescentis and, as well as B. longum are more dominant in adults. Increasingly, evidence is accumulating which shows beneficial effect of supplementation with bifidobacteria for the improvement of human health conditions ranging from protection against infection to different extra- and intra-intestinal positive effects. Moreover, bifidobacteria can be associated with the production of a number of potentially health promoting metabolites including short chain fatty acids, conjugated linoleic acid and bacteriocins. The aim of this mini-review is to describe the bifidobacteria composition changes associated with different stages in life, highlighting their beneficial role, as well as their presence in commonly known disease states.

Probiotics and the Gut Immune System: Indirect Regulation.

Science.gov (United States)

La Fata, Giorgio; Weber, Peter; Mohajeri, M Hasan

2018-03-01

The gastrointestinal tract (GIT) represents the largest interface between the human organism and the external environment. In the lumen and upper part of the mucus layer, this organ hosts an enormous number of microorganisms whose composition affects the functions of the epithelial barrier and the gut immune system. Consequentially, the microorganisms in the GIT influence the health status of the organism. Probiotics are living microorganisms which, in specific conditions, confer a health benefit to the host. Among others, probiotics have immunomodulatory properties that usually act directly by (a) increasing the activity of macrophages or natural killer cells, (b) modulating the secretion of immunoglobulins or cytokines, or indirectly by (c) enhancing the gut epithelial barrier, (d) altering the mucus secretion, and (e) competitive exclusion of other (pathogenic) bacteria. This review focuses on specific bacteria strains with indirect immunomodulatory properties. Particularly, we describe here the mechanisms through which specific probiotics enhance the gut epithelial barrier and modulate mucus production. Moreover, we describe the antimicrobial properties of specific bacteria strains. Recent data suggest that multiple pathologies are associated with an unbalanced gut microflora (dysbiosis). Although the cause-effect relationship between pathology and gut microflora is not yet well established, consumption of specific probiotics may represent a powerful tool to re-establish gut homeostasis and promote gut health.

“Omic” investigations of protozoa and worms for a deeper understanding of the human gut “parasitome”

Science.gov (United States)

Marzano, Valeria; Mancinelli, Livia; Bracaglia, Giorgia; Del Chierico, Federica; Vernocchi, Pamela; Di Girolamo, Francesco; Garrone, Stefano; Tchidjou Kuekou, Hyppolite; D’Argenio, Patrizia; Dallapiccola, Bruno; Urbani, Andrea

2017-01-01

The human gut has been continuously exposed to a broad spectrum of intestinal organisms, including viruses, bacteria, fungi, and parasites (protozoa and worms), over millions of years of coevolution, and plays a central role in human health. The modern lifestyles of Western countries, such as the adoption of highly hygienic habits, the extensive use of antimicrobial drugs, and increasing globalisation, have dramatically altered the composition of the gut milieu, especially in terms of its eukaryotic “citizens.” In the past few decades, numerous studies have highlighted the composition and role of human intestinal bacteria in physiological and pathological conditions, while few investigations exist on gut parasites and particularly on their coexistence and interaction with the intestinal microbiota. Studies of the gut “parasitome” through “omic” technologies, such as (meta)genomics, transcriptomics, proteomics, and metabolomics, are herein reviewed to better understand their role in the relationships between intestinal parasites, host, and resident prokaryotes, whether pathogens or commensals. Systems biology–based profiles of the gut “parasitome” under physiological and severe disease conditions can indeed contribute to the control of infectious diseases and offer a new perspective of omics-assisted tropical medicine. PMID:29095820

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.

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

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

The human gut microbiota as a reservoir for antimicrobial resistance genes

NARCIS (Netherlands)

Bülow, E.

2015-01-01

In the last decades, the emergence and spread of resistant opportunistic pathogens is compromising the effectiveness of antimicrobial therapies. Understanding the emergence and global spread of drug-resistant microorganisms is thus crucial to combat antimicrobial resistance. The human gut harbors a

Diet, gut microbiota and cognition.

Science.gov (United States)

Proctor, Cicely; Thiennimitr, Parameth; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2017-02-01

The consumption of a diet high in fat and sugar can lead to the development of obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease and cognitive decline. In the human gut, the trillions of harmless microorganisms harboured in the host's gastrointestinal tract are called the 'gut microbiota'. Consumption of a diet high in fat and sugar changes the healthy microbiota composition which leads to an imbalanced microbial population in the gut, a phenomenon known as "gut dysbiosis". It has been shown that certain types of gut microbiota are linked to the pathogenesis of obesity. In addition, long-term consumption of a high fat diet is associated with cognitive decline. It has recently been proposed that the gut microbiota is part of a mechanistic link between the consumption of a high fat diet and the impaired cognition of an individual, termed "microbiota-gut-brain axis". In this complex relationship between the gut, the brain and the gut microbiota, there are several types of gut microbiota and host mechanisms involved. Most of these mechanisms are still poorly understood. Therefore, this review comprehensively summarizes the current evidence from mainly in vivo (rodent and human) studies of the relationship between diet, gut microbiota and cognition. The possible mechanisms that the diet and the gut microbiota have on cognition are also presented and discussed.

Effect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism

DEFF Research Database (Denmark)

Mikkelsen, Kristian H; Frost, Morten; Bahl, Martin Iain

2015-01-01

The gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans. Meal tests...... with measurements of postprandial glucose tolerance and postprandial release of insulin and gut hormones were performed before, immediately after and 6 weeks after a 4-day, broad-spectrum, per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in a group of 12 lean...... and glucose tolerant males. Faecal samples were collected for culture-based assessment of changes in gut microbiota composition. Acute and dramatic reductions in the abundance of a representative set of gut bacteria was seen immediately following the antibiotic course, but no changes in postprandial glucose...

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.

More than 9,000,000 unique genes in human gut bacterial community: estimating gene numbers inside a human body.

Science.gov (United States)

Yang, Xing; Xie, Lu; Li, Yixue; Wei, Chaochun

2009-06-29

Estimating the number of genes in human genome has been long an important problem in computational biology. With the new conception of considering human as a super-organism, it is also interesting to estimate the number of genes in this human super-organism. We presented our estimation of gene numbers in the human gut bacterial community, the largest microbial community inside the human super-organism. We got 552,700 unique genes from 202 complete human gut bacteria genomes. Then, a novel gene counting model was built to check the total number of genes by combining culture-independent sequence data and those complete genomes. 16S rRNAs were used to construct a three-level tree and different counting methods were introduced for the three levels: strain-to-species, species-to-genus, and genus-and-up. The model estimates that the total number of genes is about 9,000,000 after those with identity percentage of 97% or up were merged. By combining completed genomes currently available and culture-independent sequencing data, we built a model to estimate the number of genes in human gut bacterial community. The total number of genes is estimated to be about 9 million. Although this number is huge, we believe it is underestimated. This is an initial step to tackle this gene counting problem for the human super-organism. It will still be an open problem in the near future. The list of genomes used in this paper can be found in the supplementary table.

Gut microbiota in toxicological risk assessment of drugs and chemicals: The need of hour.

Science.gov (United States)

Velmurugan, Ganesan

2018-03-06

The advent of industrial revolution caused a large inflow of synthetic chemicals for medical, agricultural, industrial and other purposes in the world. In general, these chemicals were subjected to toxicological risk assessment for human health and ecology before release for public use. But today we are witnessing a negative impact of some of these chemicals on human health and environment indicating an underestimation of toxic effects by current risk assessment protocol. Recent studies established gut microbiota as one of the key player in intercession of toxicity of drugs and synthetic chemicals. Hence, the need of the hour is to include the assessment for microbiota specifically gut microbiota in human toxicological risk assessment protocol. Herewith we are proposing a framework for assessment of gut microbiota upon exposure to drugs or chemicals.

Antibiotic-induced gut microbiota disruption during human endotoxemia: a randomised controlled study.

Science.gov (United States)

Lankelma, Jacqueline M; Cranendonk, Duncan R; Belzer, Clara; de Vos, Alex F; de Vos, Willem M; van der Poll, Tom; Wiersinga, W Joost

2017-09-01

The gut microbiota is essential for the development of the intestinal immune system. Animal models have suggested that the gut microbiota also acts as a major modulator of systemic innate immunity during sepsis. Microbiota disruption by broad-spectrum antibiotics could thus have adverse effects on cellular responsiveness towards invading pathogens. As such, the use of antibiotics may attribute to immunosuppression as seen in sepsis. We aimed to test whether disruption of the gut microbiota affects systemic innate immune responses during endotoxemia in healthy subjects. In this proof-of-principle intervention trial, 16 healthy young men received either no treatment or broad-spectrum antibiotics (ciprofloxacin, vancomycin and metronidazole) for 7 days, after which all were administered lipopolysaccharide intravenously to induce a transient sepsis-like syndrome. At various time points, blood and faeces were sampled. Gut microbiota diversity was significantly lowered by the antibiotic treatment in all subjects. Clinical parameters, neutrophil influx, cytokine production, coagulation activation and endothelial activation during endotoxemia were not different between antibiotic-pretreated and control individuals. Antibiotic treatment had no impact on blood leucocyte responsiveness to various Toll-like receptor ligands and clinically relevant causative agents of sepsis ( Streptococcus pneumoniae, Klebsiella pneumoniae, Escherichia coli ) during endotoxemia. These findings suggest that gut microbiota disruption by broad-spectrum antibiotics does not affect systemic innate immune responses in healthy subjects during endotoxemia in humans, disproving our hypothesis. Further research is needed to test this hypothesis in critically ill patients. These data underline the importance of translating findings in mice to humans. ClinicalTrials.gov (NCT02127749; Pre-results). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

Cultivation-based multiplex phenotyping of human gut microbiota allows targeted recovery of previously uncultured bacteria

DEFF Research Database (Denmark)

Rettedal, Elizabeth; Gumpert, Heidi; Sommer, Morten

2014-01-01

The human gut microbiota is linked to a variety of human health issues and implicated in antibiotic resistance gene dissemination. Most of these associations rely on culture-independent methods, since it is commonly believed that gut microbiota cannot be easily or sufficiently cultured. Here, we...... microbiota. Based on the phenotypic mapping, we tailor antibiotic combinations to specifically select for previously uncultivated bacteria. Utilizing this method we cultivate and sequence the genomes of four isolates, one of which apparently belongs to the genus Oscillibacter; uncultivated Oscillibacter...

The Role of the Gut Microbiota in Childhood Obesity.

Science.gov (United States)

Pihl, Andreas Friis; Fonvig, Cilius Esmann; Stjernholm, Theresa; Hansen, Torben; Pedersen, Oluf; Holm, Jens-Christian

2016-08-01

Childhood and adolescent obesity has reached epidemic proportions worldwide. The pathogenesis of obesity is complex and multifactorial, in which genetic and environmental contributions seem important. The gut microbiota is increasingly documented to be involved in the dysmetabolism associated with obesity. We conducted a systematic search for literature available before October 2015 in the PubMed and Scopus databases, focusing on the interplay between the gut microbiota, childhood obesity, and metabolism. The review discusses the potential role of the bacterial component of the human gut microbiota in childhood and adolescent-onset obesity, with a special focus on the factors involved in the early development of the gut bacterial ecosystem, and how modulation of this microbial community might serve as a basis for new therapeutic strategies in combating childhood obesity. A vast number of variables are influencing the gut microbial ecology (e.g., the host genetics, delivery method, diet, age, environment, and the use of pre-, pro-, and antibiotics); but the exact physiological processes behind these relationships need to be clarified. Exploring the role of the gut microbiota in the development of childhood obesity may potentially reveal new strategies for obesity prevention and treatment.

Gut microbiota modulate T cell trafficking into human colorectal cancer.

Science.gov (United States)

Cremonesi, Eleonora; Governa, Valeria; Garzon, Jesus Francisco Glaus; Mele, Valentina; Amicarella, Francesca; Muraro, Manuele Giuseppe; Trella, Emanuele; Galati-Fournier, Virginie; Oertli, Daniel; Däster, Silvio Raffael; Droeser, Raoul A; Weixler, Benjamin; Bolli, Martin; Rosso, Raffaele; Nitsche, Ulrich; Khanna, Nina; Egli, Adrian; Keck, Simone; Slotta-Huspenina, Julia; Terracciano, Luigi M; Zajac, Paul; Spagnoli, Giulio Cesare; Eppenberger-Castori, Serenella; Janssen, Klaus-Peter; Borsig, Lubor; Iezzi, Giandomenica

2018-02-06

Tumour-infiltrating lymphocytes (TILs) favour survival in human colorectal cancer (CRC). Chemotactic factors underlying their recruitment remain undefined. We investigated chemokines attracting T cells into human CRCs, their cellular sources and microenvironmental triggers. Expression of genes encoding immune cell markers, chemokines and bacterial 16S ribosomal RNA (16SrRNA) was assessed by quantitative reverse transcription-PCR in fresh CRC samples and corresponding tumour-free tissues. Chemokine receptor expression on TILs was evaluated by flow cytometry on cell suspensions from digested tissues. Chemokine production by CRC cells was evaluated in vitro and in vivo, on generation of intraperitoneal or intracecal tumour xenografts in immune-deficient mice. T cell trafficking was assessed on adoptive transfer of human TILs into tumour-bearing mice. Gut flora composition was analysed by 16SrRNA sequencing. CRC infiltration by distinct T cell subsets was associated with defined chemokine gene signatures, including CCL5, CXCL9 and CXCL10 for cytotoxic T lymphocytes and T-helper (Th)1 cells; CCL17, CCL22 and CXCL12 for Th1 and regulatory T cells; CXCL13 for follicular Th cells; and CCL20 and CCL17 for interleukin (IL)-17-producing Th cells. These chemokines were expressed by tumour cells on exposure to gut bacteria in vitro and in vivo. Their expression was significantly higher in intracecal than in intraperitoneal xenografts and was dramatically reduced by antibiotic treatment of tumour-bearing mice. In clinical samples, abundance of defined bacteria correlated with high chemokine expression, enhanced T cell infiltration and improved survival. Gut microbiota stimulate chemokine production by CRC cells, thus favouring recruitment of beneficial T cells into tumour tissues. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Faecalibacterium gut colonization is accelerated by presence of older siblings

DEFF Research Database (Denmark)

Laursen, Martin Frederik; Laursen, Rikke Pilmann; Larnkjær, Anni

2017-01-01

-inflammatory properties. However, factors affecting the colonization of F. prausnitzii in the human gut during early life are very poorly understood. By analysis of 16S rRNA amplicon sequencing data from three separate infant study populations, we determined the colonization dynamics of Faecalibacterium and factors...... affecting its establishment in the gut. We found that in particular, the presence of older siblings was consistently associated with Faecalibacterium gut colonization during late infancy and conclude that acquisition of Faecalibacterium is very likely to be accelerated through transfer between siblings....... IMPORTANCEFaecalibacterium prausnitzii has been suggested to constitute a key marker of a healthy gut, yet the factors shaping the colonization of this highly oxygen-sensitive, non-spore-forming species in the intestinal environment remain poorly understood. Here, we provide evidence from three separate infant study...

Gut microbiota diversity and human diseases: should we reintroduce key predators in our ecosystem?

Directory of Open Access Journals (Sweden)

Alexis eMosca

2016-03-01

Full Text Available Most of the Human diseases affecting westernized countries are associated with dysbiosis and loss of microbial diversity in the gut microbiota. The Western way of life, with a wide use of antibiotics and other environmental triggers, may reduce the number of bacterial predators leading to a decrease in microbial diversity of the Human gut. We argue that this phenomenon is similar to the process of ecosystem impoverishment in macro ecology where human activity decreases ecological niches, the size of predator populations and finally the biodiversity. Such pauperization is fundamental since it reverses the evolution processes, drives life backward into diminished complexity, stability and adaptability. A simple therapeutic approach could thus be to reintroduce bacterial predators and restore a bacterial diversity of the host microbiota.

Individual diet has sex-dependent effects on vertebrate gut microbiota

Science.gov (United States)

Bolnick, Daniel I.; Snowberg, Lisa K.; Hirsch, Philipp E.; Lauber, Christian L.; Org, Elin; Parks, Brian; Lusis, Aldons J.; Knight, Rob; Caporaso, J. Gregory; Svanbäck, Richard

2014-01-01

Vertebrates harbour diverse communities of symbiotic gut microbes. Host diet is known to alter microbiota composition, implying that dietary treatments might alleviate diseases arising from altered microbial composition (‘dysbiosis’). However, it remains unclear whether diet effects are general or depend on host genotype. Here we show that gut microbiota composition depends on interactions between host diet and sex within populations of wild and laboratory fish, laboratory mice and humans. Within each of two natural fish populations (threespine stickleback and Eurasian perch), among-individual diet variation is correlated with individual differences in gut microbiota. However, these diet–microbiota associations are sex dependent. We document similar sex-specific diet–microbiota correlations in humans. Experimental diet manipulations in laboratory stickleback and mice confirmed that diet affects microbiota differently in males versus females. The prevalence of such genotype by environment (sex by diet) interactions implies that therapies to treat dysbiosis might have sex-specific effects. PMID:25072318

Wheat bran cereal, human gut bacteria and subjective wellbeing

OpenAIRE

Smith, Andrew; Deaville, Eddie; Gibson, Glenn

2018-01-01

Research has shown that consumption of high fiber breakfast cereal is associated with improved subjective well-being, especially increased energy. One possible explanation of these results is through metabolism by gut bacteria and concomitant production of metabolites that influence psychological and gastrointestinal (GI) welfare. This was examined in the present study to determine whether consumption of wheat bran could modulate the composition of the GI microbiota. This human volunteer stud...

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.

Gut Pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes.

Science.gov (United States)

Saad, Rama; Rizkallah, Mariam R; Aziz, Ramy K

2012-11-30

The influence of resident gut microbes on xenobiotic metabolism has been investigated at different levels throughout the past five decades. However, with the advance in sequencing and pyrotagging technologies, addressing the influence of microbes on xenobiotics had to evolve from assessing direct metabolic effects on toxins and botanicals by conventional culture-based techniques to elucidating the role of community composition on drugs metabolic profiles through DNA sequence-based phylogeny and metagenomics. Following the completion of the Human Genome Project, the rapid, substantial growth of the Human Microbiome Project (HMP) opens new horizons for studying how microbiome compositional and functional variations affect drug action, fate, and toxicity (pharmacomicrobiomics), notably in the human gut. The HMP continues to characterize the microbial communities associated with the human gut, determine whether there is a common gut microbiome profile shared among healthy humans, and investigate the effect of its alterations on health. Here, we offer a glimpse into the known effects of the gut microbiota on xenobiotic metabolism, with emphasis on cases where microbiome variations lead to different therapeutic outcomes. We discuss a few examples representing how the microbiome interacts with human metabolic enzymes in the liver and intestine. In addition, we attempt to envisage a roadmap for the future implications of the HMP on therapeutics and personalized medicine.

The Effect of Pomegranate (Punica granatum L.) Byproducts and Ellagitannins on the Growth of Human Gut Bacteria

Science.gov (United States)

The consumption of pomegranate products leads to a significant accumulation of ellagitannins in the large intestines, where they interact with complex gut microflora. This study investigated the effect of pomegranate tannin constituents on the growth of various species of human gut bacteria. Our r...

The gut microbiota and inflammatory noncommunicable diseases

DEFF Research Database (Denmark)

West, Christina E; Renz, Harald; Jenmalm, Maria C

2015-01-01

Rapid environmental transition and modern lifestyles are likely driving changes in the biodiversity of the human gut microbiota. With clear effects on physiologic, immunologic, and metabolic processes in human health, aberrations in the gut microbiome and intestinal homeostasis have the capacity...... for neurodevelopment and mental health. These diverse multisystem influences have sparked interest in strategies that might favorably modulate the gut microbiota to reduce the risk of many NCDs. For example, specific prebiotics promote favorable intestinal colonization, and their fermented products have anti....... In human subjects it has been successfully used in cases of Clostridium difficile infection and IBD, although controlled trials are lacking for IBD. Here we discuss relationships between gut colonization and inflammatory NCDs and gut microbiota modulation strategies for their treatment and prevention....

Comprehensive analysis of polyamine transport and biosynthesis in the dominant human gut bacteria: Potential presence of novel polyamine metabolism and transport genes.

Science.gov (United States)

Sugiyama, Yuta; Nara, Misaki; Sakanaka, Mikiyasu; Gotoh, Aina; Kitakata, Aya; Okuda, Shujiro; Kurihara, Shin

2017-12-01

Recent studies have reported that polyamines in the colonic lumen might affect animal health and these polyamines are thought to be produced by gut bacteria. In the present study, we measured the concentrations of three polyamines (putrescine, spermidine, and spermine) in cells and culture supernatants of 32 dominant human gut bacterial species in their growing and stationary phases. Combining polyamine concentration analysis in culture supernatant and cells with available genomic information showed that novel polyamine biosynthetic proteins and transporters were present in dominant human gut bacteria. Based on these findings, we suggested strategies for optimizing polyamine concentrations in the human colonic lumen via regulation of genes responsible for polyamine biosynthesis and transport in the dominant human gut bacteria. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Fungal Frontier: A Comparative Analysis of Methods Used in the Study of the Human Gut Mycobiome.

Science.gov (United States)

Huseyin, Chloe E; Rubio, Raul Cabrera; O'Sullivan, Orla; Cotter, Paul D; Scanlan, Pauline D

2017-01-01

The human gut is host to a diverse range of fungal species, collectively referred to as the gut "mycobiome". The gut mycobiome is emerging as an area of considerable research interest due to the potential roles of these fungi in human health and disease. However, there is no consensus as to what the best or most suitable methodologies available are with respect to characterizing the human gut mycobiome. The aim of this study is to provide a comparative analysis of several previously published mycobiome-specific culture-dependent and -independent methodologies, including choice of culture media, incubation conditions (aerobic versus anaerobic), DNA extraction method, primer set and freezing of fecal samples to assess their relative merits and suitability for gut mycobiome analysis. There was no significant effect of media type or aeration on culture-dependent results. However, freezing was found to have a significant effect on fungal viability, with significantly lower fungal numbers recovered from frozen samples. DNA extraction method had a significant effect on DNA yield and quality. However, freezing and extraction method did not have any impact on either α or β diversity. There was also considerable variation in the ability of different fungal-specific primer sets to generate PCR products for subsequent sequence analysis. Through this investigation two DNA extraction methods and one primer set was identified which facilitated the analysis of the mycobiome for all samples in this study. Ultimately, a diverse range of fungal species were recovered using both approaches, with Candida and Saccharomyces identified as the most common fungal species recovered using culture-dependent and culture-independent methods, respectively. As has been apparent from ecological surveys of the bacterial fraction of the gut microbiota, the use of different methodologies can also impact on our understanding of gut mycobiome composition and therefore requires careful consideration

Early impairment of gut function and gut flora supporting a role for alteration of gastrointestinal mucosa in human immunodeficiency virus pathogenesis

NARCIS (Netherlands)

Gori, Andrea; Tincati, Camilla; Rizzardini, Giuliano; Torti, Carlo; Quirino, Tiziana; Haarman, Monique; Ben Amor, Kaouther; van Schaik, Jacqueline; Vriesema, Aldwin; Knol, Jan; Marchetti, Giulia; Welling, Gjalt; Clerici, Mario

Our results show that impairment of the gastrointestinal tracts in human immunodeficiency virus (HIV)-positive patients is present in the early phases of HIV disease. This impairment is associated with alterations in gut microbiota and intestinal inflammatory parameters. These findings support the

IL-2 Enhances Gut Homing Potential of Human Naive Regulatory T Cells Early in Life.

Science.gov (United States)

Hsu, Peter S; Lai, Catherine L; Hu, Mingjing; Santner-Nanan, Brigitte; Dahlstrom, Jane E; Lee, Cheng Hiang; Ajmal, Ayesha; Bullman, Amanda; Arbuckle, Susan; Al Saedi, Ahmed; Gacis, Lou; Nambiar, Reta; Williams, Andrew; Wong, Melanie; Campbell, Dianne E; Nanan, Ralph

2018-06-15

Recent evidence suggests early environmental factors are important for gut immune tolerance. Although the role of regulatory T (Treg) cells for gut immune homeostasis is well established, the development and tissue homing characteristics of Treg cells in children have not been studied in detail. In this article, we studied the development and homing characteristics of human peripheral blood Treg cell subsets and potential mechanisms inducing homing molecule expression in healthy children. We found contrasting patterns of circulating Treg cell gut and skin tropism, with abundant β7 integrin + Treg cells at birth and increasing cutaneous lymphocyte Ag (CLA + ) Treg cells later in life. β7 integrin + Treg cells were predominantly naive, suggesting acquisition of Treg cell gut tropism early in development. In vitro, IL-7 enhanced gut homing but reduced skin homing molecule expression in conventional T cells, whereas IL-2 induced a similar effect only in Treg cells. This effect was more pronounced in cord compared with adult blood. Our results suggest that early in life, naive Treg cells may be driven for gut tropism by their increased sensitivity to IL-2-induced β7 integrin upregulation, implicating a potential role of IL-2 in gut immune tolerance during this critical period of development. Copyright © 2018 by The American Association of Immunologists, Inc.

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.

The Human Gut Microbiota

NARCIS (Netherlands)

Harmsen, Hermie J. M.; de Goffau, Marcus. C.; Schwiertz, A

2016-01-01

The microbiota in our gut performs many different essential functions that help us to stay healthy. These functions include vitamin production, regulation of lipid metabolism and short chain fatty acid production as fuel for epithelial cells and regulation of gene expression. There is a very

Gut Pharmacomicrobiomics: the tip of an iceberg of complex interactions between drugs and gut-associated microbes

Directory of Open Access Journals (Sweden)

Saad Rama

2012-11-01

Full Text Available Abstract The influence of resident gut microbes on xenobiotic metabolism has been investigated at different levels throughout the past five decades. However, with the advance in sequencing and pyrotagging technologies, addressing the influence of microbes on xenobiotics had to evolve from assessing direct metabolic effects on toxins and botanicals by conventional culture-based techniques to elucidating the role of community composition on drugs metabolic profiles through DNA sequence-based phylogeny and metagenomics. Following the completion of the Human Genome Project, the rapid, substantial growth of the Human Microbiome Project (HMP opens new horizons for studying how microbiome compositional and functional variations affect drug action, fate, and toxicity (pharmacomicrobiomics, notably in the human gut. The HMP continues to characterize the microbial communities associated with the human gut, determine whether there is a common gut microbiome profile shared among healthy humans, and investigate the effect of its alterations on health. Here, we offer a glimpse into the known effects of the gut microbiota on xenobiotic metabolism, with emphasis on cases where microbiome variations lead to different therapeutic outcomes. We discuss a few examples representing how the microbiome interacts with human metabolic enzymes in the liver and intestine. In addition, we attempt to envisage a roadmap for the future implications of the HMP on therapeutics and personalized medicine.

Ecophysiological consequences of alcoholism on human gut microbiota: implications for ethanol-related pathogenesis of colon cancer.

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Tsuruya, Atsuki; Kuwahara, Akika; Saito, Yuta; Yamaguchi, Haruhiko; Tsubo, Takahisa; Suga, Shogo; Inai, Makoto; Aoki, Yuichi; Takahashi, Seiji; Tsutsumi, Eri; Suwa, Yoshihide; Morita, Hidetoshi; Kinoshita, Kenji; Totsuka, Yukari; Suda, Wataru; Oshima, Kenshiro; Hattori, Masahira; Mizukami, Takeshi; Yokoyama, Akira; Shimoyama, Takefumi; Nakayama, Toru

2016-06-13

Chronic consumption of excess ethanol increases the risk of colorectal cancer. The pathogenesis of ethanol-related colorectal cancer (ER-CRC) is thought to be partly mediated by gut microbes. Specifically, bacteria in the colon and rectum convert ethanol to acetaldehyde (AcH), which is carcinogenic. However, the effects of chronic ethanol consumption on the human gut microbiome are poorly understood, and the role of gut microbes in the proposed AcH-mediated pathogenesis of ER-CRC remains to be elaborated. Here we analyse and compare the gut microbiota structures of non-alcoholics and alcoholics. The gut microbiotas of alcoholics were diminished in dominant obligate anaerobes (e.g., Bacteroides and Ruminococcus) and enriched in Streptococcus and other minor species. This alteration might be exacerbated by habitual smoking. These observations could at least partly be explained by the susceptibility of obligate anaerobes to reactive oxygen species, which are increased by chronic exposure of the gut mucosa to ethanol. The AcH productivity from ethanol was much lower in the faeces of alcoholic patients than in faeces of non-alcoholic subjects. The faecal phenotype of the alcoholics could be rationalised based on their gut microbiota structures and the ability of gut bacteria to accumulate AcH from ethanol.

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

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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

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

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

Challenges in simulating the human gut for understanding the role of the microbiota in obesity.

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Aguirre, M; Venema, K

2017-02-07

There is an elevated incidence of cases of obesity worldwide. Therefore, the development of strategies to tackle this condition is of vital importance. This review focuses on the necessity of optimising in vitro systems to model human colonic fermentation in obese subjects. This may allow to increase the resolution and the physiological relevance of the information obtained from this type of studies when evaluating the potential role that the human gut microbiota plays in obesity. In light of the parameters that are currently used for the in vitro simulation of the human gut (which are mostly based on information derived from healthy subjects) and the possible difference with an obese condition, we propose to revise and improve specific standard operating procedures.

In vitro fermentation of alginate and its derivatives by human gut microbiota.

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Li, Miaomiao; Li, Guangsheng; Shang, Qingsen; Chen, Xiuxia; Liu, Wei; Pi, Xiong'e; Zhu, Liying; Yin, Yeshi; Yu, Guangli; Wang, Xin

2016-06-01

Alginate (Alg) has a long history as a food ingredient in East Asia. However, the human gut microbes responsible for the degradation of alginate and its derivatives have not been fully understood yet. Here, we report that alginate and the low molecular polymer derivatives of mannuronic acid oligosaccharides (MO) and guluronic acid oligosaccharides (GO) can be completely degraded and utilized at various rates by fecal microbiota obtained from six Chinese individuals. However, the derivative of propylene glycol alginate sodium sulfate (PSS) was not hydrolyzed. The bacteria having a pronounced ability to degrade Alg, MO and GO were isolated from human fecal samples and were identified as Bacteroides ovatus, Bacteroides xylanisolvens, and Bacteroides thetaiotaomicron. Alg, MO and GO can increase the production level of short chain fatty acids (SCFA), but GO generates the highest level of SCFA. Our data suggest that alginate and its derivatives could be degraded by specific bacteria in the human gut, providing the basis for the impacts of alginate and its derivates as special food additives on human health. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gut Microbiota in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis: Current Applications and Future Perspectives

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Lang, Yue

2018-01-01

The gut environment and gut microbiome dysbiosis have been demonstrated to significantly influence a range of disorders in humans, including obesity, diabetes, rheumatoid arthritis, and multiple sclerosis (MS). MS is an autoimmune disease affecting the central nervous system (CNS). The etiology of MS is not clear, and it should involve both genetic and extrinsic factors. The extrinsic factors responsible for predisposition to MS remain elusive. Recent studies on MS and its animal model, experimental autoimmune encephalomyelitis (EAE), have found that gastrointestinal microbiota may play an important role in the pathogenesis of MS/EAE. Thus, gut microbiome adjustment may be a future direction of treatment in MS. In this review, we discuss the characteristics of the gut microbiota, the connection between the brain and the gut, and the changes in gut microbiota in MS/EAE, and we explore the possibility of applying microbiota therapies in patients with MS. PMID:29805314

Metabolic niche of a prominent sulfate-reducing human gut bacterium.

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Rey, Federico E; Gonzalez, Mark D; Cheng, Jiye; Wu, Meng; Ahern, Philip P; Gordon, Jeffrey I

2013-08-13

Sulfate-reducing bacteria (SRB) colonize the guts of ∼50% of humans. We used genome-wide transposon mutagenesis and insertion-site sequencing, RNA-Seq, plus mass spectrometry to characterize genetic and environmental factors that impact the niche of Desulfovibrio piger, the most common SRB in a surveyed cohort of healthy US adults. Gnotobiotic mice were colonized with an assemblage of sequenced human gut bacterial species with or without D. piger and fed diets with different levels and types of carbohydrates and sulfur sources. Diet was a major determinant of functions expressed by this artificial nine-member community and of the genes that impact D. piger fitness; the latter includes high- and low-affinity systems for using ammonia, a limiting resource for D. piger in mice consuming a polysaccharide-rich diet. Although genes involved in hydrogen consumption and sulfate reduction are necessary for its colonization, varying dietary-free sulfate levels did not significantly alter levels of D. piger, which can obtain sulfate from the host in part via cross-feeding mediated by Bacteroides-encoded sulfatases. Chondroitin sulfate, a common dietary supplement, increased D. piger and H2S levels without compromising gut barrier integrity. A chondroitin sulfate-supplemented diet together with D. piger impacted the assemblage's substrate utilization preferences, allowing consumption of more reduced carbon sources and increasing the abundance of the H2-producing Actinobacterium, Collinsella aerofaciens. Our findings provide genetic and metabolic details of how this H2-consuming SRB shapes the responses of a microbiota to diet ingredients and a framework for examining how individuals lacking D. piger differ from those who harbor it.

Connections between the human gut microbiome and gestational diabetes mellitus.

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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.

Enterotypes influence temporal changes in gut microbiota

DEFF Research Database (Denmark)

Roager, Henrik Munch; Licht, Tine Rask; Kellebjerg Poulsen, Sanne

The human gut microbiota plays an important role for human health. The question is whether we can modulate the gut microbiota by changing diet. During a 6-month, randomised, controlled dietary intervention, the effect of consuming a diet following the New Nordic Diet recommendations (NND......) as opposed to Average Danish Diet (ADD) on the gut microbiota in humans (n=62) was investigated. Quantitative PCR analysis showed that the microbiota did not change significantly by the intervention. Nevertheless, by stratifying subjects into two enterotypes, distinguished by the Prevotella/Bacteroides ratio...... (P/B), we were able to detect significant changes in the gut microbiota composition resulting from the interventions. Subjects with a high-P/B experienced more pronounced changes in the gut microbiota composition than subjects with a low-P/B. The study is the first to indicate that enterotypes...

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

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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.

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

Gut Microbiota, Obesity and Metabolic Dysfunction

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Anna Meiliana

2011-12-01

Full Text Available BACKGROUND: The prevalence of obesity and related disorders such as metabolic syndrome and diabetes has vastly increased throughout the world. Recent insights have generated an entirely new perspective suggesting that our microbiota might be involved in the development of these disorders. This represents an area of scientific need, opportunity and challenge. The insights gleaned should help to address several pressing global health problems. CONTENT: Our bowels have two major roles: the digestion and absorption of nutrients and the maintenance of a barrier against the external environment. They fulfill these functions in the context of, and with the help from, tens of trillions of resident microbes, known as the gut microbiota. Studies have demonstrated that obesity and metabolic syndrome may be associated with profound microbiotal changes, and the induction of a metabolic syndrome phenotype through fecal transplants corroborates the important role of the microbiota in this disease. Dietary composition and caloric intake appear to swiftly regulate intestinal microbial composition and function. SUMMARY: The interaction of the intestinal microbial world with its host, and its mutual regulation, will become one of the important topics of biomedical research and will provide us with further insights at the interface of microbiota, metabolism, metabolic syndrome, and obesity. A better understanding of the interaction between certain diets and the human gut microbiome should help to develop new guidelines for feeding humans at various time points in their life, help to improve global human health, and establish ways to prevent or treat various food-related diseases. KEYWORDS: gut microbiota, obesity, metabolic syndrome, type 2 diabetes.

Bacterial growth, flow, and mixing shape human gut microbiota density and composition.

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Arnoldini, Markus; Cremer, Jonas; Hwa, Terence

2018-03-13

The human gut microbiota is highly dynamic, and host physiology and diet exert major influences on its composition. In our recent study, we integrated new quantitative measurements on bacterial growth physiology with a reanalysis of published data on human physiology to build a comprehensive modeling framework. This can generate predictions of how changes in different host factors influence microbiota composition. For instance, hydrodynamic forces in the colon, along with colonic water absorption that manifests as transit time, exert a major impact on microbiota density and composition. This can be mechanistically explained by their effect on colonic pH which directly affects microbiota competition for food. In this addendum, we describe the underlying analysis in more detail. In particular, we discuss the mixing dynamics of luminal content by wall contractions and its implications for bacterial growth and density, as well as the broader implications of our insights for the field of gut microbiota research.

Effect of dextransucrase cellobiose acceptor products on the growth of human gut bacteria

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The selective fermentation by human gut bacteria of gluco-oligosaccharides obtained from the reaction between the glucosyl group of sucrose and cellobiose, catalyzed by dextransucrases from Leuconostoc mesenteroides, has been evaluated. Oligosaccharides were fractionated according to their molecula...

The gut microbiome as a target for prevention and treatment of hyperglycaemia in type 2 diabetes: from current human evidence to future possibilities.

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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

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....

MALINA: a web service for visual analytics of human gut microbiota whole-genome metagenomic reads.

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Tyakht, Alexander V; Popenko, Anna S; Belenikin, Maxim S; Altukhov, Ilya A; Pavlenko, Alexander V; Kostryukova, Elena S; Selezneva, Oksana V; Larin, Andrei K; Karpova, Irina Y; Alexeev, Dmitry G

2012-12-07

MALINA is a web service for bioinformatic analysis of whole-genome metagenomic data obtained from human gut microbiota sequencing. As input data, it accepts metagenomic reads of various sequencing technologies, including long reads (such as Sanger and 454 sequencing) and next-generation (including SOLiD and Illumina). It is the first metagenomic web service that is capable of processing SOLiD color-space reads, to authors' knowledge. The web service allows phylogenetic and functional profiling of metagenomic samples using coverage depth resulting from the alignment of the reads to the catalogue of reference sequences which are built into the pipeline and contain prevalent microbial genomes and genes of human gut microbiota. The obtained metagenomic composition vectors are processed by the statistical analysis and visualization module containing methods for clustering, dimension reduction and group comparison. Additionally, the MALINA database includes vectors of bacterial and functional composition for human gut microbiota samples from a large number of existing studies allowing their comparative analysis together with user samples, namely datasets from Russian Metagenome project, MetaHIT and Human Microbiome Project (downloaded from http://hmpdacc.org). MALINA is made freely available on the web at http://malina.metagenome.ru. The website is implemented in JavaScript (using Ext JS), Microsoft .NET Framework, MS SQL, Python, with all major browsers supported.

Gut Microbiota: Impact of probiotics, prebiotics, synbiotics, pharmabiotics and postbiotics on human health

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Multidisciplinary approaches enabled a better understanding of the connection between human gut microbes and health. This knowledge is rapidly changing how we think about probiotics and related –biotics (prebiotics, synbiotics, pharmabiotics and postbiotics). Functional –omics approaches are very im...

Absorption of environmental polonium-210 by the human gut

International Nuclear Information System (INIS)

Hunt, G.J.; Allington, D.J.

1993-01-01

Current values for the gut absorption factor of plutonium- 210 ( 210 Po) are based on very few human data, yet the dose due to 210 Po is an important component of the dose to man through food as a result of natural sources of radiation. In this study, three male and three female adult volunteers ate supplies of brown crab meat containing natural concentrations of 210 Po, which are analysed from sub-samples. Daily urine and faecal samples, taken for 3 days before and up to 3 weeks after ingestion, were also analysed. Values of apparent absorption were derived from the faecal measurements; estimates of the true absorption were derived taking account of endogenous faecal excretion on the basis of existing data for intravenous administration. The results appear to suggest that the gut absorption factor in current use for 210 Po (in connection with ingestion in food) should be increased from 0.1-03 to about 0.8. The implications for estimates of dose due to this exposure pathway are noted. (author)

Absorption of environmental polonium-210 by the human gut

Energy Technology Data Exchange (ETDEWEB)

Hunt, G J; Allington, D J [Ministry of Agriculture, Fisheries and Food, Lowestoft (United Kingdom). Fisheries Radiobiological Lab.

1993-06-01

Current values for the gut absorption factor of plutonium- 210 ([sup 210]Po) are based on very few human data, yet the dose due to [sup 210]Po is an important component of the dose to man through food as a result of natural sources of radiation. In this study, three male and three female adult volunteers ate supplies of brown crab meat containing natural concentrations of [sup 210]Po, which are analysed from sub-samples. Daily urine and faecal samples, taken for 3 days before and up to 3 weeks after ingestion, were also analysed. Values of apparent absorption were derived from the faecal measurements; estimates of the true absorption were derived taking account of endogenous faecal excretion on the basis of existing data for intravenous administration. The results appear to suggest that the gut absorption factor in current use for [sup 210]Po (in connection with ingestion in food) should be increased from 0.1-03 to about 0.8. The implications for estimates of dose due to this exposure pathway are noted. (author).

SadA-Expressing Staphylococci in the Human Gut Show Increased Cell Adherence and Internalization

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Arif Luqman

2018-01-01

Full Text Available Summary: A subgroup of biogenic amines, the so-called trace amines (TAs, are produced by mammals and bacteria and can act as neuromodulators. In the genus Staphylococcus, certain species are capable of producing TAs through the activity of staphylococcal aromatic amino acid decarboxylase (SadA. SadA decarboxylates aromatic amino acids to produce TAs, as well as dihydroxy phenylalanine and 5-hydroxytryptophan to thus produce the neurotransmitters dopamine and serotonin. SadA-expressing staphylococci were prevalent in the gut of most probands, where they are part of the human intestinal microflora. Furthermore, sadA-expressing staphylococci showed increased adherence to HT-29 cells and 2- to 3-fold increased internalization. Internalization and adherence was also increased in a sadA mutant in the presence of tryptamine. The α2-adrenergic receptor is required for enhanced adherence and internalization. Thus, staphylococci in the gut might contribute to gut activity and intestinal colonization. : Luqman et al. examine the sadA gene and argue that it contributes to TAs. They found that neuromodulator-producing staphylococci were present in the gut of most probands. The produced neuromodulators enhanced the adherence and internalization of staphylococci to cells in culture. Keywords: adherence, aromatic amino acid decarboxylase, gut microbiota, internalization, neuromodulator, neurotransmitter, staphylococcus

Comparison of the distal gut microbiota from people and animals in Africa.

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Ellis, Richard J; Bruce, Kenneth D; Jenkins, Claire; Stothard, J Russell; Ajarova, Lilly; Mugisha, Lawrence; Viney, Mark E

2013-01-01

The gut microbiota plays a key role in the maintenance of healthy gut function as well as many other aspects of health. High-throughput sequence analyses have revealed the composition of the gut microbiota, showing that there is a core signature to the human gut microbiota, as well as variation in its composition between people. The gut microbiota of animals is also being investigated. We are interested in the relationship between bacterial taxa of the human gut microbiota and those in the gut microbiota of domestic and semi-wild animals. While it is clear that some human gut bacterial pathogens come from animals (showing that human--animal transmission occurs), the extent to which the usually non-pathogenic commensal taxa are shared between humans and animals has not been explored. To investigate this we compared the distal gut microbiota of humans, cattle and semi-captive chimpanzees in communities that are geographically sympatric in Uganda. The gut microbiotas of these three host species could be distinguished by the different proportions of bacterial taxa present. We defined multiple operational taxonomic units (OTUs) by sequence similarity and found evidence that some OTUs were common between human, cattle and chimpanzees, with the largest number of shared OTUs occurring between chimpanzees and humans, as might be expected with their close physiological similarity. These results show the potential for the sharing of usually commensal bacterial taxa between humans and other animals. This suggests that further investigation of this phenomenon is needed to fully understand how it drives the composition of human and animal gut microbiotas.

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

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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.

Probiotics, Prebiotics, and Synbiotics: Gut and Beyond

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Usha Vyas

2012-01-01

Full Text Available The human intestinal tract has been colonized by thousands of species of bacteria during the coevolution of man and microbes. Gut-borne microbes outnumber the total number of body tissue cells by a factor of ten. Recent metagenomic analysis of the human gut microbiota has revealed the presence of some 3.3 million genes, as compared to the mere 23 thousand genes present in the cells of the tissues in the entire human body. Evidence for various beneficial roles of the intestinal microbiota in human health and disease is expanding rapidly. Perturbation of the intestinal microbiota may lead to chronic diseases such as autoimmune diseases, colon cancers, gastric ulcers, cardiovascular disease, functional bowel diseases, and obesity. Restoration of the gut microbiota may be difficult to accomplish, but the use of probiotics has led to promising results in a large number of well-designed (clinical studies. Microbiomics has spurred a dramatic increase in scientific, industrial, and public interest in probiotics and prebiotics as possible agents for gut microbiota management and control. Genomics and bioinformatics tools may allow us to establish mechanistic relationships among gut microbiota, health status, and the effects of drugs in the individual. This will hopefully provide perspectives for personalized gut microbiota management.

Gut microbes in correlation with mood: case study in a closed experimental human life support system.

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Li, L; Su, Q; Xie, B; Duan, L; Zhao, W; Hu, D; Wu, R; Liu, H

2016-08-01

Gut microbial community, which may influence our mood, can be shaped by modulating the gut ecosystem through dietary strategies. Understanding the gut-brain correlationship in healthy people is important for maintenance of mental health and prevention of mental illnesses. A case study on the correlation between gut microbial alternation and mood swing of healthy adults was conducted in a closed human life support system during a 105-day experiment. Gut microbial community structures were analyzed using high-throughput sequencing every 2 weeks. A profile of mood states questionnaire was used to record the mood swings. Correlation between gut microbes and mood were identified with partial least squares discrimination analysis. Microbial community structures in the three healthy adults were strongly correlated with mood states. Bacterial genera Roseburia, Phascolarctobacterium, Lachnospira, and Prevotella had potential positive correlation with positive mood, while genera Faecalibacterium, Bifidobacterium, Bacteroides, Parabacteroides, and Anaerostipes were correlated with negative mood. Among which, Faecalibacterium spp. had the highest abundance, and showed a significant negative correlation with mood. Our results indicated that the composition of microbial community could play a role in emotional change in mentally physically healthy adults. © 2016 John Wiley & Sons Ltd.

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

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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...

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

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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.

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

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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.

Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health.

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Vernocchi, Pamela; Del Chierico, Federica; Putignani, Lorenza

2016-01-01

The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies.

Starch Catabolism by a Prominent Human Gut Symbiont Is Directed by the Recognition of Amylose Helices

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Koropatkin, Nicole M.; Martens, Eric C.; Gordon, Jeffrey I.; Smith, Thomas J. (WU); (Danforth)

2009-01-12

The human gut microbiota performs functions that are not encoded in our Homo sapiens genome, including the processing of otherwise undigestible dietary polysaccharides. Defining the structures of proteins involved in the import and degradation of specific glycans by saccharolytic bacteria complements genomic analysis of the nutrient-processing capabilities of gut communities. Here, we describe the atomic structure of one such protein, SusD, required for starch binding and utilization by Bacteroides thetaiotaomicron, a prominent adaptive forager of glycans in the distal human gut microbiota. The binding pocket of this unique {alpha}-helical protein contains an arc of aromatic residues that complements the natural helical structure of starch and imposes this conformation on bound maltoheptaose. Furthermore, SusD binds cyclic oligosaccharides with higher affinity than linear forms. The structures of several SusD/oligosaccharide complexes reveal an inherent ligand recognition plasticity dominated by the three-dimensional conformation of the oligosaccharides rather than specific interactions with the composite sugars.

The gut microbiota, obesity and insulin resistance

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The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflam...

Insights into the human gut microbiome and cardiovascular diseases

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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.

Disruption of the Gut Ecosystem by Antibiotics

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2018-01-01

The intestinal microbiota is a complex ecosystem consisting of various microorganisms that expands human genetic repertoire and therefore affects human health and disease. The metabolic processes and signal transduction pathways of the host and intestinal microorganisms are intimately linked, and abnormal progression of each process leads to changes in the intestinal environment. Alterations in microbial communities lead to changes in functional structures based on the metabolites produced in the gut, and these environmental changes result in various bacterial infections and chronic enteric inflammatory diseases. Here, we illustrate how antibiotics are associated with an increased risk of antibiotic-associated diseases by driving intestinal environment changes that favor the proliferation and virulence of pathogens. Understanding the pathogenesis caused by antibiotics would be a crucial key to the treatment of antibiotic-associated diseases by mitigating changes in the intestinal environment and restoring it to its original state. PMID:29214770

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

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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.

In vitro culture and characterization of enteric neural precursor cells from human gut biopsy specimens using polymer scaffold.

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Krishnamohan, Janardhanam; Senthilnathan, Venugopal S; Vaikundaraman, Tirunelveli Muthiah; Srinivasan, Thangavelu; Balamurugan, Madasamy; Iwasaki, Masaru; Preethy, Senthilkumar; Abraham, Samuel Jk

2013-08-01

In vitro expansion and characterization of neural precursor cells from human gut biopsy specimens with or without Hirschsprung's disease using a novel thermoreversible gelation polymer (TGP) is reported aiming at a possible future treatment. Gut biopsy samples were obtained from five patients undergoing gut resection for Hirschsprung's disease (n = 1) or gastrointestinal disorders (n = 4). Cells isolated from the smooth muscle layer and the myenteric plexus were cultured in two groups for 18 to 28 days; Group I: conventional culture as earlier reported and Group II: using TGP scaffold. Neurosphere like bodies (NLBs) were observed in the cultures between 8th to 12th day and H & E staining was positive for neural cells in both groups including aganglionic gut portion from the Hirschsprung's disease patient. Immunohistochemistry using S-100 and neuron specific enolase (NSE) was positive in both groups but the TGP group (Group II) showed more number of cells with intense cytoplasmic granular positivity for both NSE and S-100 compared to Group I. TGP supports the in vitro expansion of human gut derived neuronal cells with seemingly better quality NLBs. Animal Studies can be tried to validate their functional outcome by transplanting the NLBs with TGP scaffolds to see whether this can enhance the outcome of cell based therapies for Hirschsprung's disease.

[Gut microbiota: Description, role and pathophysiologic implications].

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Landman, C; Quévrain, E

2016-06-01

The human gut contains 10(14) bacteria and many other micro-organisms such as Archaea, viruses and fungi. Studying the gut microbiota showed how this entity participates to gut physiology and beyond this to human health, as a real "hidden organ". In this review, we aimed to bring information about gut microbiota, its structure, its roles and its implication in human pathology. After bacterial colonization in infant, intestinal microbial composition is unique for each individual although more than 95% can be assigned to four major phyla. The use of culture independent methods and more recently the development of high throughput sequencing allowed to depict precisely gut microbiota structure and diversity as well as its alteration in diseases. Gut microbiota is implicated in the maturation of the host immune system and in many fundamental metabolic pathways including sugars and proteins fermentation and metabolism of bile acids and xenobiotics. Imbalance of gut microbial populations or dysbiosis has important functional consequences and is implicated in many digestive diseases (inflammatory bowel diseases, colorectal cancer, etc.) but also in obesity and autism. These observations have led to a surge of studies exploring therapeutics which aims to restore gut microbiota equilibrium such as probiotics or fecal microbiota transplantation. But recent research also investigates biological activity of microbial products which could lead to interesting therapeutics leads. Copyright © 2015 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

The role of gut microbiota in human metabolism

NARCIS (Netherlands)

Vrieze, A.

2013-01-01

This thesis supports the hypothesis that gut microbiota can be viewed as an ‘exteriorised organ’ that contributes to energy metabolism and the modulation of our immune system. Following Koch’s postulates, it has now been shown that gut microbiota are associated with metabolic disease and that these

Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans : A Randomized Double-Blind Placebo-Controlled Trial

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Reijnders, Dorien; Goossens, Gijs H.; Hermes, Gerben D. A.; Neis, Evelien P. J. G.; van der Beek, Christina M.; Most, Jasper; Holst, Jens J.; Lenaerts, Kaatje; Kootte, Ruud S.; Nieuwdorp, Max; Groen, Albert K.; Damink, Steven W. M. Olde; Boekschoten, Mark V.; Smidt, Hauke; Zoetendal, Erwin G.; Dejong, Cornelis H. C.; Blaak, Ellen E.

2016-01-01

The gut microbiota has been implicated in obesity and cardiometabolic diseases, although evidence in humans is scarce. We investigated how gut microbiota manipulation by antibiotics (7-day administration of amoxicillin, vancomycin, or placebo) affects host metabolism in 57 obese, prediabetic men.

Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans: A Randomized Double-Blind Placebo-Controlled Trial

NARCIS (Netherlands)

Reijnders, Dorien; Goossens, Gijs H.; Hermes, Gerben D. A.; Neis, Evelien P. J. G.; van der Beek, Christina M.; Most, Jasper; Holst, Jens J.; Lenaerts, Kaatje; Kootte, Ruud S.; Nieuwdorp, Max; Groen, Albert K.; Olde Damink, Steven W. M.; Boekschoten, Mark V.; Smidt, Hauke; Zoetendal, Erwin G.; Dejong, Cornelis H. C.; Blaak, Ellen E.

2016-01-01

The gut microbiota has been implicated in obesity and cardiometabolic diseases, although evidence in humans is scarce. We investigated how gut microbiota manipulation by antibiotics (7-day administration of amoxicillin, vancomycin, or placebo) affects host metabolism in 57 obese, prediabetic men.

Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production

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Wu, Gary D; Compher, Charlene; Chen, Eric Z; Smith, Sarah A; Shah, Rachana D; Bittinger, Kyle; Chehoud, Christel; Albenberg, Lindsey G; Nessel, Lisa; Gilroy, Erin; Star, Julie; Weljie, Aalim M; Flint, Harry J; Metz, David C; Bennett, Michael J; Li, Hongzhe; Bushman, Frederic D; Lewis, James D

2015-01-01

Objective The consumption of an agrarian diet is associated with a reduced risk for many diseases associated with a ‘Westernised’ lifestyle. Studies suggest that diet affects the gut microbiota, which subsequently influences the metabolome, thereby connecting diet, microbiota and health. However, the degree to which diet influences the composition of the gut microbiota is controversial. Murine models and studies comparing the gut microbiota in humans residing in agrarian versus Western societies suggest that the influence is large. To separate global environmental influences from dietary influences, we characterised the gut microbiota and the host metabolome of individuals consuming an agrarian diet in Western society. Design and results Using 16S rRNA-tagged sequencing as well as plasma and urinary metabolomic platforms, we compared measures of dietary intake, gut microbiota composition and the plasma metabolome between healthy human vegans and omnivores, sampled in an urban USA environment. Plasma metabolome of vegans differed markedly from omnivores but the gut microbiota was surprisingly similar. Unlike prior studies of individuals living in agrarian societies, higher consumption of fermentable substrate in vegans was not associated with higher levels of faecal short chain fatty acids, a finding confirmed in a 10-day controlled feeding experiment. Similarly, the proportion of vegans capable of producing equol, a soy-based gut microbiota metabolite, was less than that was reported in Asian societies despite the high consumption of soy-based products. Conclusions Evidently, residence in globally distinct societies helps determine the composition of the gut microbiota that, in turn, influences the production of diet-dependent gut microbial metabolites. PMID:25431456

Use of dietary indices to control for diet in human gut microbiota studies.

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Bowyer, Ruth C E; Jackson, Matthew A; Pallister, Tess; Skinner, Jane; Spector, Tim D; Welch, Ailsa A; Steves, Claire J

2018-04-25

Environmental factors have a large influence on the composition of the human gut microbiota. One of the most influential and well-studied is host diet. To assess and interpret the impact of non-dietary factors on the gut microbiota, we endeavoured to determine the most appropriate method to summarise community variation attributable to dietary effects. Dietary habits are multidimensional with internal correlations. This complexity can be simplified by using dietary indices that quantify dietary variance in a single measure and offer a means of controlling for diet in microbiota studies. However, to date, the applicability of different dietary indices to gut microbiota studies has not been assessed. Here, we use food frequency questionnaire (FFQ) data from members of the TwinsUK cohort to create three different dietary measures applicable in western-diet populations: The Healthy Eating Index (HEI), the Mediterranean Diet Score (MDS) and the Healthy Food Diversity index (HFD-Index). We validate and compare these three indices to determine which best summarises dietary influences on gut microbiota composition. All three indices were independently validated using established measures of health, and all were significantly associated with microbiota measures; the HEI had the highest t values in models of alpha diversity measures, and had the highest number of associations with microbial taxa. Beta diversity analyses showed the HEI explained the greatest variance of microbiota composition. In paired tests between twins discordant for dietary index score, the HEI was associated with the greatest variation of taxa and twin dissimilarity. We find that the HEI explains the most variance in, and has the strongest association with, gut microbiota composition in a western (UK) population, suggesting that it may be the best summary measure to capture gut microbiota variance attributable to habitual diet in comparable populations.

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

Gut microbiota and metabolic syndrome.

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Festi, Davide; Schiumerini, Ramona; Eusebi, Leonardo Henry; Marasco, Giovanni; Taddia, Martina; Colecchia, Antonio

2014-11-21

Gut microbiota exerts a significant role in the pathogenesis of the metabolic syndrome, as confirmed by studies conducted both on humans and animal models. Gut microbial composition and functions are strongly influenced by diet. This complex intestinal "superorganism" seems to affect host metabolic balance modulating energy absorption, gut motility, appetite, glucose and lipid metabolism, as well as hepatic fatty storage. An impairment of the fine balance between gut microbes and host's immune system could culminate in the intestinal translocation of bacterial fragments and the development of "metabolic endotoxemia", leading to systemic inflammation and insulin resistance. Diet induced weight-loss and bariatric surgery promote significant changes of gut microbial composition, that seem to affect the success, or the inefficacy, of treatment strategies. Manipulation of gut microbiota through the administration of prebiotics or probiotics could reduce intestinal low grade inflammation and improve gut barrier integrity, thus, ameliorating metabolic balance and promoting weight loss. However, further evidence is needed to better understand their clinical impact and therapeutic use.

An Extracellular Cell-Attached Pullulanase Confers Branched α-Glucan Utilization in Human Gut Lactobacillus acidophilus.

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Møller, Marie S; Goh, Yong Jun; Rasmussen, Kasper Bøwig; Cypryk, Wojciech; Celebioglu, Hasan Ufuk; Klaenhammer, Todd R; Svensson, Birte; Abou Hachem, Maher

2017-06-15

Of the few predicted extracellular glycan-active enzymes, glycoside hydrolase family 13 subfamily 14 (GH13_14) pullulanases are the most common in human gut lactobacilli. These enzymes share a unique modular organization, not observed in other bacteria, featuring a catalytic module, two starch binding modules, a domain of unknown function, and a C-terminal surface layer association protein (SLAP) domain. Here, we explore the specificity of a representative of this group of pullulanases, Lactobacillus acidophilus Pul13_14 ( La Pul13_14), and its role in branched α-glucan metabolism in the well-characterized Lactobacillus acidophilus NCFM, which is widely used as a probiotic. Growth experiments with L. acidophilus NCFM on starch-derived branched substrates revealed a preference for α-glucans with short branches of about two to three glucosyl moieties over amylopectin with longer branches. Cell-attached debranching activity was measurable in the presence of α-glucans but was repressed by glucose. The debranching activity is conferred exclusively by La Pul13_14 and is abolished in a mutant strain lacking a functional La Pul13_14 gene. Hydrolysis kinetics of recombinant La Pul13_14 confirmed the preference for short-branched α-glucan oligomers consistent with the growth data. Curiously, this enzyme displayed the highest catalytic efficiency and the lowest K m reported for a pullulanase. Inhibition kinetics revealed mixed inhibition by β-cyclodextrin, suggesting the presence of additional glucan binding sites besides the active site of the enzyme, which may contribute to the unprecedented substrate affinity. The enzyme also displays high thermostability and higher activity in the acidic pH range, reflecting adaptation to the physiologically challenging conditions in the human gut. IMPORTANCE Starch is one of the most abundant glycans in the human diet. Branched α-1,6-glucans in dietary starch and glycogen are nondegradable by human enzymes and constitute a

Establishment of normal gut microbiota is compromised under excessive hygiene conditions.

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Bettina Schmidt

Full Text Available BACKGROUND: Early gut colonization events are purported to have a major impact on the incidence of infectious, inflammatory and autoimmune diseases in later life. Hence, factors which influence this process may have important implications for both human and animal health. Previously, we demonstrated strong influences of early-life environment on gut microbiota composition in adult pigs. Here, we sought to further investigate the impact of limiting microbial exposure during early life on the development of the pig gut microbiota. METHODOLOGY/PRINCIPAL FINDINGS: Outdoor- and indoor-reared animals, exposed to the microbiota in their natural rearing environment for the first two days of life, were transferred to an isolator facility and adult gut microbial diversity was analyzed by 16S rRNA gene sequencing. From a total of 2,196 high-quality 16S rRNA gene sequences, 440 phylotypes were identified in the outdoor group and 431 phylotypes in the indoor group. The majority of clones were assigned to the four phyla Firmicutes (67.5% of all sequences, Proteobacteria (17.7%, Bacteroidetes (13.5% and to a lesser extent, Actinobacteria (0.1%. Although the initial maternal and environmental microbial inoculum of isolator-reared animals was identical to that of their naturally-reared littermates, the microbial succession and stabilization events reported previously in naturally-reared outdoor animals did not occur. In contrast, the gut microbiota of isolator-reared animals remained highly diverse containing a large number of distinct phylotypes. CONCLUSIONS/SIGNIFICANCE: The results documented here indicate that establishment and development of the normal gut microbiota requires continuous microbial exposure during the early stages of life and this process is compromised under conditions of excessive hygiene.

Modulation of Gut Microbiota in Pathological States

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Yulan Wang

2017-02-01

Full Text Available The human microbiota is an aggregate of microorganisms residing in the human body, mostly in the gastrointestinal tract (GIT. Our gut microbiota evolves with us and plays a pivotal role in human health and disease. In recent years, the microbiota has gained increasing attention due to its impact on host metabolism, physiology, and immune system development, but also because the perturbation of the microbiota may result in a number of diseases. The gut microbiota may be linked to malignancies such as gastric cancer and colorectal cancer. It may also be linked to disorders such as nonalcoholic fatty liver disease (NAFLD; obesity and diabetes, which are characterized as “lifestyle diseases” of the industrialized world; coronary heart disease; and neurological disorders. Although the revolution in molecular technologies has provided us with the necessary tools to study the gut microbiota more accurately, we need to elucidate the relationships between the gut microbiota and several human pathologies more precisely, as understanding the impact that the microbiota plays in various diseases is fundamental for the development of novel therapeutic strategies. Therefore, the aim of this review is to provide the reader with an updated overview of the importance of the gut microbiota for human health and the potential to manipulate gut microbial composition for purposes such as the treatment of antibiotic-resistant Clostridium difficile (C. difficile infections. The concept of altering the gut community by microbial intervention in an effort to improve health is currently in its infancy. However, the therapeutic implications appear to be very great. Thus, the removal of harmful organisms and the enrichment of beneficial microbes may protect our health, and such efforts will pave the way for the development of more rational treatment options in the future.

Xenobiotic Metabolism and Gut Microbiomes.

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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.

Human Gut Microbiota Predicts Susceptibility to Vibrio cholerae Infection.

Science.gov (United States)

Midani, Firas S; Weil, Ana A; Chowdhury, Fahima; Begum, Yasmin A; Khan, Ashraful I; Debela, Meti D; Durand, Heather K; Reese, Aspen T; Nimmagadda, Sai N; Silverman, Justin D; Ellis, Crystal N; Ryan, Edward T; Calderwood, Stephen B; Harris, Jason B; Qadri, Firdausi; David, Lawrence A; LaRocque, Regina C

2018-04-12

Cholera is a public health problem worldwide and the risk factors for infection are only partially understood. We prospectively studied household contacts of cholera patients to compare those who were infected with those who were not. We constructed predictive machine learning models of susceptibility using baseline gut microbiota data. We identified bacterial taxa associated with susceptibility to Vibrio cholerae infection and tested these taxa for interactions with V. cholerae in vitro. We found that machine learning models based on gut microbiota predicted V. cholerae infection as well as models based on known clinical and epidemiological risk factors. A 'predictive gut microbiota' of roughly 100 bacterial taxa discriminated between contacts who developed infection and those who did not. Susceptibility to cholera was associated with depleted levels of microbes from the phylum Bacteroidetes. By contrast, a microbe associated with cholera by our modeling framework, Paracoccus aminovorans, promoted the in vitro growth of V. cholerae. Gut microbiota structure, clinical outcome, and age were also linked. These findings support the hypothesis that abnormal gut microbial communities are a host factor related to V. cholerae susceptibility.

Short-term effect of antibiotics on human gut microbiota.

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Suchita Panda

Full Text Available From birth onwards, the human gut microbiota rapidly increases in diversity and reaches an adult-like stage at three years of age. After this age, the composition may fluctuate in response to external factors such as antibiotics. Previous studies have shown that resilience is not complete months after cessation of the antibiotic intake. However, little is known about the short-term effects of antibiotic intake on the gut microbial community. Here we examined the load and composition of the fecal microbiota immediately after treatment in 21 patients, who received broad-spectrum antibiotics such as fluoroquinolones and β-lactams. A fecal sample was collected from all participants before treatment and one week after for microbial load and community composition analyses by quantitative PCR and pyrosequencing of the 16S rRNA gene, respectively. Fluoroquinolones and β-lactams significantly decreased microbial diversity by 25% and reduced the core phylogenetic microbiota from 29 to 12 taxa. However, at the phylum level, these antibiotics increased the Bacteroidetes/Firmicutes ratio (p = 0.0007, FDR = 0.002. At the species level, our findings unexpectedly revealed that both antibiotic types increased the proportion of several unknown taxa belonging to the Bacteroides genus, a Gram-negative group of bacteria (p = 0.0003, FDR<0.016. Furthermore, the average microbial load was affected by the treatment. Indeed, the β-lactams increased it significantly by two-fold (p = 0.04. The maintenance of or possible increase detected in microbial load and the selection of Gram-negative over Gram-positive bacteria breaks the idea generally held about the effect of broad-spectrum antibiotics on gut microbiota.

Regulatory effect of paraprobiotic Lactobacillus gasseri CP2305 on gut environment and function

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Tomonori Sugawara

2016-03-01

Full Text Available Background: Lactobacillus gasseri CP2305 (CP2305 is a strain of Lactobacillus isolated from a stool sample from a healthy adult that showed beneficial effects on health as a paraprobiotic. In a previous study, we demonstrated that CP2305-fermented heat-treated milk modified gut functions more than artificially acidified sour milk. Thus, the regulatory activity of the former beverage was attributed to the inactivated CP2305 cells. Objective: The aim of this study was to elucidate the contribution of non-viable paraprobiotic CP2305 cells to regulating human gut functions. We thus conducted a randomized, placebo-controlled, double-blinded parallel group trial. Design: The trial included 118 healthy participants with relatively low or high stool frequencies. The test beverage was prepared by adding 1×1010 washed, heat-treated, and dried CP2305 cells directly to the placebo beverage. The participants ingested a bottle of the assigned beverage daily for 3 weeks and answered daily questionnaires about defecation and quality of life. Fecal samples were collected and the fecal characteristics, microbial metabolite contents of the feces and composition of fecal microbiota were evaluated. Results: The number of evacuations and the scores for fecal odors were significantly improved in the group that consumed the CP2305-containing beverage compared with those of the group that consumed the placebo (p=0.035 and p=0.040, respectively. Regarding the fecal contents of microbial metabolites, the level of fecal p-cresol was significantly decreased in the CP2305 group relative to that of the placebo group (p=0.013. The Bifidobacterium content of the intestinal microbiota was significantly increased in the CP2305 group relative to that of the placebo group (p<0.008, whereas the content of Clostridium cluster IV was significantly decreased (p<0.003. The parasympathetic nerve activity of the autonomic nervous system became dominant and the total power of autonomic

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

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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.

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

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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.

Relationship between Human Gut Microbiota and Interleukin 6 Levels in Overweight and Obese Adults

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Background: Gut microbial diversity and abundance can profoundly impact human health. Research has shown that obese individuals are likely to have altered microbiota compared to lean individuals. Obesity is often considered a pro-inflammatory state, however the relationship between microbiota and i...

Obesity changes the human gut mycobiome

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Mar Rodríguez, M.; Pérez, Daniel; Javier Chaves, Felipe; Esteve, Eduardo; Marin-Garcia, Pablo; Xifra, Gemma; Vendrell, Joan; Jové, Mariona; Pamplona, Reinald; Ricart, Wifredo; Portero-Otin, Manuel; Chacón, Matilde R.; Fernández Real, José Manuel

2015-01-01

The human intestine is home to a diverse range of bacterial and fungal species, forming an ecological community that contributes to normal physiology and disease susceptibility. Here, the fungal microbiota (mycobiome) in obese and non-obese subjects was characterized using Internal Transcribed Spacer (ITS)-based sequencing. The results demonstrate that obese patients could be discriminated by their specific fungal composition, which also distinguished metabolically “healthy” from “unhealthy” obesity. Clusters according to genus abundance co-segregated with body fatness, fasting triglycerides and HDL-cholesterol. A preliminary link to metabolites such as hexadecanedioic acid, caproic acid and N-acetyl-L-glutamic acid was also found. Mucor racemosus and M. fuscus were the species more represented in non-obese subjects compared to obese counterparts. Interestingly, the decreased relative abundance of the Mucor genus in obese subjects was reversible upon weight loss. Collectively, these findings suggest that manipulation of gut mycobiome communities might be a novel target in the treatment of obesity. PMID:26455903

Screening assays of termite gut microbes that potentially as probiotic for human to digest cellulose as new food source

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Abdullah, R.; Ananda, K. R. T.; Wijanarka

2018-05-01

According to UN, earth population will increase approximately 7.3 billion people up to 11.2 billion from 2015 until 2100. On the other side, food needs are not balance with the availability of food on earth. People of the world need solution for a new food source. By cellulose digesting ability, people analyzed can consume cellulose as the new food source to get glucose. The aims of research is obtaining termite gut cellulase bacteria selected which is potential as probiotic to split cellulose. Method used was as follows; isolation of termite gut microbes, microbial cellulase purification by screening method and probiotic test includes microbial pathogenicity test and human stomach acid and salt osmotic concentration resistance test. The result shows, 3 pure isolates of termite gut microbes can break down cellulose in the medium 1% CMC and 0.1% congo red (indicator of cellulose degradation activity) and life at pH 2- 2.5 and osmotic salt condition. Two isolates show the activity of gamma hemolysis (non-pathogenic in terms of pathogenicity on human blood). In conclusion, there are isolated termite gut microbes can be used as probiotic candidate for human to digest cellulose of the new food source for global food scarcity era.

Differential bacterial capture and transport preferences facilitate co-growth on dietary xylan in the human gut

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Leth, Maria Louise; Ejby, Morten; Workman, Christopher

2018-01-01

Metabolism of dietary glycans is pivotal in shaping the human gut microbiota. However, the mechanisms that promote competition for glycans among gut commensals remain unclear. Roseburia intestinalis, an abundant butyrate-producing Firmicute, is a key degrader of the major dietary fibre xylan...... of capture and transport preferences as a possible strategy to facilitate co-growth on abundant dietary fibres and may offer a unique route to manipulate the microbiota based on glycan transport preferences in therapeutic interventions to boost distinct taxa....

Antivirulence activity of the human gut metabolome.

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Antunes, L Caetano M; McDonald, Julie A K; Schroeter, Kathleen; Carlucci, Christian; Ferreira, Rosana B R; Wang, Melody; Yurist-Doutsch, Sophie; Hira, Gill; Jacobson, Kevan; Davies, Julian; Allen-Vercoe, Emma; Finlay, B Brett

2014-07-29

The mammalian gut contains a complex assembly of commensal microbes termed microbiota. Although much has been learned about the role of these microbes in health, the mechanisms underlying these functions are ill defined. We have recently shown that the mammalian gut contains thousands of small molecules, most of which are currently unidentified. Therefore, we hypothesized that these molecules function as chemical cues used by hosts and microbes during their interactions in health and disease. Thus, a search was initiated to identify molecules produced by the microbiota that are sensed by pathogens. We found that a secreted molecule produced by clostridia acts as a strong repressor of Salmonella virulence, obliterating expression of the Salmonella pathogenicity island 1 as well as host cell invasion. It has been known for decades that the microbiota protects its hosts from invading pathogens, and these data suggest that chemical sensing may be involved in this phenomenon. Further investigations should reveal the exact biological role of this molecule as well as its therapeutic potential. Importance: Microbes can communicate through the production and sensing of small molecules. Within the complex ecosystem formed by commensal microbes living in and on the human body, it is likely that these molecular messages are used extensively during the interactions between different microbial species as well as with host cells. Deciphering such a molecular dialect will be fundamental to our understanding of host-microbe interactions in health and disease and may prove useful for the design of new therapeutic strategies that target these mechanisms of communication. Copyright © 2014 Antunes et al.

SadA-Expressing Staphylococci in the Human Gut Show Increased Cell Adherence and Internalization.

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Luqman, Arif; Nega, Mulugeta; Nguyen, Minh-Thu; Ebner, Patrick; Götz, Friedrich

2018-01-09

A subgroup of biogenic amines, the so-called trace amines (TAs), are produced by mammals and bacteria and can act as neuromodulators. In the genus Staphylococcus, certain species are capable of producing TAs through the activity of staphylococcal aromatic amino acid decarboxylase (SadA). SadA decarboxylates aromatic amino acids to produce TAs, as well as dihydroxy phenylalanine and 5-hydroxytryptophan to thus produce the neurotransmitters dopamine and serotonin. SadA-expressing staphylococci were prevalent in the gut of most probands, where they are part of the human intestinal microflora. Furthermore, sadA-expressing staphylococci showed increased adherence to HT-29 cells and 2- to 3-fold increased internalization. Internalization and adherence was also increased in a sadA mutant in the presence of tryptamine. The α2-adrenergic receptor is required for enhanced adherence and internalization. Thus, staphylococci in the gut might contribute to gut activity and intestinal colonization. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Targeting the ecology within: The role of the gut-brain axis and human microbiota in drug addiction.

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Skosnik, Patrick D; Cortes-Briones, Jose A

2016-08-01

Despite major advances in our understanding of the brain using traditional neuroscience, reliable and efficacious treatments for drug addiction have remained elusive. Hence, the time has come to utilize novel approaches, particularly those drawing upon contemporary advances in fields outside of established neuroscience and psychiatry. Put another way, the time has come for a paradigm shift in the addiction sciences. Apropos, a revolution in the area of human health is underway, which is occurring at the nexus between enteric microbiology and neuroscience. It has become increasingly clear that the human microbiota (the vast ecology of bacteria residing within the human organism), plays an important role in health and disease. This is not surprising, as it has been estimated that bacteria living in the human body (approximately 1kg of mass, roughly equivalent to that of the human brain) outnumber human cells 10 to 1. While advances in the understanding of the role of microbiota in other areas of human health have yielded intriguing results (e.g., Clostridium difficile, irritable bowel syndrome, autism, etc.), to date, no systematic programs of research have examined the role of microbiota in drug addiction. The current hypothesis, therefore, is that gut dysbiosis plays a key role in addictive disorders. In the context of this hypothesis, this paper provides a rationale for future research to target the "gut-brain axis" in addiction. A brief background of the gut-brain axis is provided, along with a series of hypothesis-driven ideas outlining potential treatments for addiction via manipulations of the "ecology within." Copyright © 2016 Elsevier Ltd. All rights reserved.

Digestibility of sulfated polysaccharide from the brown seaweed Ascophyllum nodosum and its effect on the human gut microbiota in vitro.

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Chen, Ligen; Xu, Wei; Chen, Dan; Chen, Guijie; Liu, Junwei; Zeng, Xiaoxiong; Shao, Rong; Zhu, Hongjun

2018-06-01

Sulfated polysaccharides from marine algae exhibit various bioactivities with potential benefits for human health and well-being. In this study, the in vitro digestibility and fermentability of polysaccharides from the brown seaweed Ascophyllum nodosum (AnPs) were examined, and the effects of AnPs on gut microbiota were determined using high-throughput sequencing technology. Salivary amylase, artificial gastric juice, and intestinal juice had no effect on AnPs, but the molecular weight of AnPs and reducing sugar decreased significantly after fermentation by gut microbiota. AnPs significantly modulated the composition of the gut microbiota; in particular, they increased the relative abundance of Bacteroidetes and Firmicutes, suggesting the potential for AnPs to decrease the risk of obesity. Furthermore, the total SCFA content after fermentation increased significantly. These results suggest that AnPs have potential uses as functional food components to improve human gut health. Copyright © 2018. Published by Elsevier B.V.

The gut microbiota and metabolic disease

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Arora, T; Bäckhed, Gert Fredrik

2016-01-01

The human gut microbiota has been studied for more than a century. However, of nonculture-based techniques exploiting next-generation sequencing for analysing the microbiota, development has renewed research within the field during the past decade. The observation that the gut microbiota......, as an environmental factor, contributes to adiposity has further increased interest in the field. The human microbiota is affected by the diet, and macronutrients serve as substrates for many microbially produced metabolites, such as short-chain fatty acids and bile acids, that may modulate host metabolism. Obesity......-producing bacteria might be causally linked to type 2 diabetes. Bariatric surgery, which promotes long-term weight loss and diabetes remission, alters the gut microbiota in both mice and humans. Furthermore, by transferring the microbiota from postbariatric surgery patients to mice, it has been demonstrated...

Microbiota-stimulated immune mechanisms to maintain gut homeostasis.

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Chung, Hachung; Kasper, Dennis Lee

2010-08-01

In recent years there has been an explosion of interest to identify microbial inhabitants of human and understand their beneficial role in health. In the gut, a symbiotic host-microbial interaction has coevolved as bacteria make essential contributions to human metabolism and bacteria in turn benefits from the nutrient-rich niche in the intestine. To maintain host-microbe coexistence, the host must protect itself against microbial invasion, injury, and overreactions to foreign food antigens, and gut microbes need protection against competing microbes and the host immune system. Perturbation of this homeostatic coexistence has been strongly associated with human disease. This review discusses how gut bacteria regulate host innate and adaptive immunity, with emphasis on how this regulation contributes to host-microbe homeostasis in the gut. Copyright 2010 Elsevier Ltd. All rights reserved.

Control of lupus nephritis by changes of gut microbiota.

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Mu, Qinghui; Zhang, Husen; Liao, Xiaofeng; Lin, Kaisen; Liu, Hualan; Edwards, Michael R; Ahmed, S Ansar; Yuan, Ruoxi; Li, Liwu; Cecere, Thomas E; Branson, David B; Kirby, Jay L; Goswami, Poorna; Leeth, Caroline M; Read, Kaitlin A; Oestreich, Kenneth J; Vieson, Miranda D; Reilly, Christopher M; Luo, Xin M

2017-07-11

Systemic lupus erythematosus, characterized by persistent inflammation, is a complex autoimmune disorder with no known cure. Immunosuppressants used in treatment put patients at a higher risk of infections. New knowledge of disease modulators, such as symbiotic bacteria, can enable fine-tuning of parts of the immune system, rather than suppressing it altogether. Dysbiosis of gut microbiota promotes autoimmune disorders that damage extraintestinal organs. Here we report a role of gut microbiota in the pathogenesis of renal dysfunction in lupus. Using a classical model of lupus nephritis, MRL/lpr, we found a marked depletion of Lactobacillales in the gut microbiota. Increasing Lactobacillales in the gut improved renal function of these mice and prolonged their survival. We used a mixture of 5 Lactobacillus strains (Lactobacillus oris, Lactobacillus rhamnosus, Lactobacillus reuteri, Lactobacillus johnsonii, and Lactobacillus gasseri), but L. reuteri and an uncultured Lactobacillus sp. accounted for most of the observed effects. Further studies revealed that MRL/lpr mice possessed a "leaky" gut, which was reversed by increased Lactobacillus colonization. Lactobacillus treatment contributed to an anti-inflammatory environment by decreasing IL-6 and increasing IL-10 production in the gut. In the circulation, Lactobacillus treatment increased IL-10 and decreased IgG2a that is considered to be a major immune deposit in the kidney of MRL/lpr mice. Inside the kidney, Lactobacillus treatment also skewed the Treg-Th17 balance towards a Treg phenotype. These beneficial effects were present in female and castrated male mice, but not in intact males, suggesting that the gut microbiota controls lupus nephritis in a sex hormone-dependent manner. This work demonstrates essential mechanisms on how changes of the gut microbiota regulate lupus-associated immune responses in mice. Future studies are warranted to determine if these results can be replicated in human subjects.

Reciprocal Prioritization to Dietary Glycans by Gut Bacteria in a Competitive Environment Promotes Stable Coexistence

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Yunus E. Tuncil

2017-10-01

Full Text Available When presented with nutrient mixtures, several human gut Bacteroides species exhibit hierarchical utilization of glycans through a phenomenon that resembles catabolite repression. However, it is unclear how closely these observed physiological changes, often measured by altered transcription of glycan utilization genes, mirror actual glycan depletion. To understand the glycan prioritization strategies of two closely related human gut symbionts, Bacteroides ovatus and Bacteroides thetaiotaomicron, we performed a series of time course assays in which both species were individually grown in a medium with six different glycans that both species can degrade. Disappearance of the substrates and transcription of the corresponding polysaccharide utilization loci (PULs were measured. Each species utilized some glycans before others, but with different priorities per species, providing insight into species-specific hierarchical preferences. In general, the presence of highly prioritized glycans repressed transcription of genes involved in utilizing lower-priority nutrients. However, transcriptional sensitivity to some glycans varied relative to the residual concentration in the medium, with some PULs that target high-priority substrates remaining highly expressed even after their target glycan had been mostly depleted. Coculturing of these organisms in the same mixture showed that the hierarchical orders generally remained the same, promoting stable coexistence. Polymer length was found to be a contributing factor for glycan utilization, thereby affecting its place in the hierarchy. Our findings not only elucidate how B. ovatus and B. thetaiotaomicron strategically access glycans to maintain coexistence but also support the prioritization of carbohydrate utilization based on carbohydrate structure, advancing our understanding of the relationships between diet and the gut microbiome.

Gut Homeostasis, Microbial Dysbiosis, and Opioids.

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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.

Handling stress may confound murine gut microbiota studies

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Cary R. Allen-Blevins

2017-01-01

Full Text Available Background Accumulating evidence indicates interactions between human milk composition, particularly sugars (human milk oligosaccharides or HMO, the gut microbiota of human infants, and behavioral effects. Some HMO secreted in human milk are unable to be endogenously digested by the human infant but are able to be metabolized by certain species of gut microbiota, including Bifidobacterium longum subsp. infantis (B. infantis, a species sensitive to host stress (Bailey & Coe, 2004. Exposure to gut bacteria like B. infantisduring critical neurodevelopment windows in early life appears to have behavioral consequences; however, environmental, physical, and social stress during this period can also have behavioral and microbial consequences. While rodent models are a useful method for determining causal relationships between HMO, gut microbiota, and behavior, murine studies of gut microbiota usually employ oral gavage, a technique stressful to the mouse. Our aim was to develop a less-invasive technique for HMO administration to remove the potential confound of gavage stress. Under the hypothesis that stress affects gut microbiota, particularly B. infantis, we predicted the pups receiving a prebiotic solution in a less-invasive manner would have the highest amount of Bifidobacteria in their gut. Methods This study was designed to test two methods, active and passive, of solution administration to mice and the effects on their gut microbiome. Neonatal C57BL/6J mice housed in a specific-pathogen free facility received increasing doses of fructooligosaccharide (FOS solution or deionized, distilled water. Gastrointestinal (GI tracts were collected from five dams, six sires, and 41 pups over four time points. Seven fecal pellets from unhandled pups and two pellets from unhandled dams were also collected. Qualitative real-time polymerase chain reaction (qRT-PCR was used to quantify and compare the amount of Bifidobacterium, Bacteroides, Bacteroidetes, and

Impact of the gut microbiota on inflammation, obesity, and metabolic disease.

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Boulangé, Claire L; Neves, Ana Luisa; Chilloux, Julien; Nicholson, Jeremy K; Dumas, Marc-Emmanuel

2016-04-20

The human gut harbors more than 100 trillion microbial cells, which have an essential role in human metabolic regulation via their symbiotic interactions with the host. Altered gut microbial ecosystems have been associated with increased metabolic and immune disorders in animals and humans. Molecular interactions linking the gut microbiota with host energy metabolism, lipid accumulation, and immunity have also been identified. However, the exact mechanisms that link specific variations in the composition of the gut microbiota with the development of obesity and metabolic diseases in humans remain obscure owing to the complex etiology of these pathologies. In this review, we discuss current knowledge about the mechanistic interactions between the gut microbiota, host energy metabolism, and the host immune system in the context of obesity and metabolic disease, with a focus on the importance of the axis that links gut microbes and host metabolic inflammation. Finally, we discuss therapeutic approaches aimed at reshaping the gut microbial ecosystem to regulate obesity and related pathologies, as well as the challenges that remain in this area.

Genes, emotions and gut microbiota: The next frontier for the gastroenterologist.

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Panduro, Arturo; Rivera-Iñiguez, Ingrid; Sepulveda-Villegas, Maricruz; Roman, Sonia

2017-05-07

Most medical specialties including the field of gastroenterology are mainly aimed at treating diseases rather than preventing them. Genomic medicine studies the health/disease process based on the interaction of the human genes with the environment. The gastrointestinal (GI) system is an ideal model to analyze the interaction between our genes, emotions and the gut microbiota. Based on the current knowledge, this mini-review aims to provide an integrated synopsis of this interaction to achieve a better understanding of the GI disorders related to bad eating habits and stress-related disease. Since human beings are the result of an evolutionary process, many biological processes such as instincts, emotions and behavior are interconnected to guarantee survival. Nourishment is a physiological need triggered by the instinct of survival to satisfy the body's energy demands. The brain-gut axis comprises a tightly connected neural-neuroendocrine circuitry between the hunger-satiety center, the dopaminergic reward system involved in the pleasure of eating and the gut microbiota that regulates which food we eat and emotions. However, genetic variations and the consumption of high-sugar and high-fat diets have overridden this energy/pleasure neurocircuitry to the point of addiction of several foodstuffs. Consequently, a gut dysbiosis generates inflammation and a negative emotional state may lead to chronic diseases. Balancing this altered processes to regain health may involve personalized-medicine and genome-based strategies. Thus, an integrated approach based on the understanding of the gene-emotions-gut microbiota interaction is the next frontier that awaits the gastroenterologist to prevent and treat GI disorders associated with obesity and negative emotions.

Emerging synbiotics and their effect on the composition and functionality of the human gut microbiota

DEFF Research Database (Denmark)

van Zanten, Gabriella Christina

Research indicates that the gut microbiota (GM) plays an important role in the health of the host and during recent years the increase in the composition and functionality of the gut microbiota has become of increasing interest. Probiotics, prebiotics or combinations hereof, so-called synbiotics......, may be used to change the composition and activity of the human GM and thereby potentially affect the host health beneficially. In this PhD study it was hypothesized that emerging synbiotics have the potential of modulating the human GM composition as well as the functionality. To gain the beneficial...... substrates. These findings indicate that the selected emerging prebiotics are able to provide a competitive advantage for NCFM and Bl-04. All the emerging synbiotics were able to induce changes in the predominant bacteria, observed as a decrease in the modified ratio of Bacteroidetes/Firmicutes (calculated...

The role of gut microbiota in health and disease : In vitro modeling of host-microbe interactions at the aerobe-anaerobe interphase of the human gut

NARCIS (Netherlands)

von Martels, Julius Z. H.; Sadabad, Mehdi Sadaghian; Bourgonje, Arno R.; Blokzijl, Tjasso; Dijkstra, Gerard; Faber, Klaas Nico; Harmsen, Hermie J. M.

The microbiota of the gut has many crucial functions in human health. Dysbiosis of the microbiota has been correlated to a large and still increasing number of diseases. Recent studies have mostly focused on analyzing the associations between disease and an aberrant microbiota composition.

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...

The gut microbiome in cardio-metabolic health

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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...

A Closer Look at Bacteroides: Phylogenetic Relationship and Genomic Implications of a Life in the Human Gut

DEFF Research Database (Denmark)

Karlsson, Fredrik H.; Ussery, David; Nielsen, Jens

2011-01-01

The human gut is extremely densely inhabited by bacteria mainly from two phyla, Bacteroidetes and Firmicutes, and there is a great interest in analyzing whole-genome sequences for these species because of their relation to human health and disease. Here, we do whole-genome comparison of 105...... of extracytoplasmic function σ factors (ECF σ factors) and two component systems for extracellular signal transduction compared to other Bacteroidetes/Chlorobi species. A whole-genome phylogenetic analysis shows a very little difference between the Parabacteroides and Bacteroides genera. Further analysis shows...... of members of the Bacteroidetes/Chlorobi phylum by whole genome comparison. Gut living Bacteroides have an enriched set of glycan, vitamin, and cofactor enzymes important for diet digestion....

Interaction between gut immunity and polysaccharides.

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Huang, Xiaojun; Nie, Shaoping; Xie, Mingyong

2017-09-22

The human gut is colonized with a vast and diverse microbial ecosystem, and these bacteria play fundamental roles in the well being of our bodies. Gut-associated lymphoid tissues, the largest mucosal immune system, should never be overlooked for their profound effect in maintaining the host immunity. Therefore, we discussed the relationship between gut immunity and host health, primarily from two aspects: the homeostasis of gut microbiota, and the function of gut-associated lymphoid tissues. Polysaccharides, widely concerned as bioactive macromolecules in recent centuries, have been proved to benefit the intestinal health. Dietary polysaccharides can improve the ratio of probiotics, regulate the intestinal microenvironment like decreasing the gut pH, and stimulate the macrophages or lymphocytes in gut tissues to fight against diseases like cancer. Based on various experimental and clinical evidence, the impacts of dietary polysaccharides on intestinal health are summarized, in order to reveal the possible immunomodulatory mechanisms of polysaccharides.

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.

21 CFR 878.4830 - Absorbable surgical gut suture.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Absorbable surgical gut suture. 878.4830 Section 878.4830 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... surgical gut suture. (a) Identification. An absorbable surgical gut suture, both plain and chromic, is an...

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.

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

Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production.

Science.gov (United States)

Wu, Gary D; Compher, Charlene; Chen, Eric Z; Smith, Sarah A; Shah, Rachana D; Bittinger, Kyle; Chehoud, Christel; Albenberg, Lindsey G; Nessel, Lisa; Gilroy, Erin; Star, Julie; Weljie, Aalim M; Flint, Harry J; Metz, David C; Bennett, Michael J; Li, Hongzhe; Bushman, Frederic D; Lewis, James D

2016-01-01

The consumption of an agrarian diet is associated with a reduced risk for many diseases associated with a 'Westernised' lifestyle. Studies suggest that diet affects the gut microbiota, which subsequently influences the metabolome, thereby connecting diet, microbiota and health. However, the degree to which diet influences the composition of the gut microbiota is controversial. Murine models and studies comparing the gut microbiota in humans residing in agrarian versus Western societies suggest that the influence is large. To separate global environmental influences from dietary influences, we characterised the gut microbiota and the host metabolome of individuals consuming an agrarian diet in Western society. Using 16S rRNA-tagged sequencing as well as plasma and urinary metabolomic platforms, we compared measures of dietary intake, gut microbiota composition and the plasma metabolome between healthy human vegans and omnivores, sampled in an urban USA environment. Plasma metabolome of vegans differed markedly from omnivores but the gut microbiota was surprisingly similar. Unlike prior studies of individuals living in agrarian societies, higher consumption of fermentable substrate in vegans was not associated with higher levels of faecal short chain fatty acids, a finding confirmed in a 10-day controlled feeding experiment. Similarly, the proportion of vegans capable of producing equol, a soy-based gut microbiota metabolite, was less than that was reported in Asian societies despite the high consumption of soy-based products. Evidently, residence in globally distinct societies helps determine the composition of the gut microbiota that, in turn, influences the production of diet-dependent gut microbial metabolites. 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/

Influence of functional food components on gut health.

Science.gov (United States)

Wan, Murphy L Y; Ling, K H; El-Nezami, Hani; Wang, M F

2018-01-30

Intestinal epithelial cells (IECs) lining the gastrointestinal tract establish a barrier between external environments and the internal milieu. An intact intestinal barrier maintains gut health and overall good health of the body by preventing from tissue injury, pathogen infection and disease development. When the intestinal barrier function is compromised, bacterial translocation can occur. Our gut microbiota also plays a fundamentally important role in health, for example, by maintaining intestinal barrier integrity, metabolism and modulating the immune system, etc. Any disruption of gut microbiota composition (also termed dysbiosis) can lead to various pathological conditions. In short, intestinal barrier and gut microbiota are two crucial factors affecting gut health. The gastrointestinal tract is a complex environment exposed to many dietary components and commensal bacteria. Dietary components are increasingly recognized to play various beneficial roles beyond basic nutrition, resulting in the development of the functional food concepts. Various dietary modifiers, including the consumption of live bacteria (probiotics) and ingestible food constituents such as prebiotics, as well as polyphenols or synbiotics (combinations of probiotics and prebiotics) are the most well characterized dietary bioactive compounds and have been demonstrated to beneficially impact the gut health and the overall well-being of the host. In this review we depict the roles of intestinal epithelium and gut microbiota in mucosal defence responses and the influence of certain functional food components on the modulation of gut health, with a particular focus on probiotics, prebiotics and polyphenols.

Human-derived gut microbiota modulates colonic secretion in mice by regulating 5-HT3 receptor expression via acetate production.

Science.gov (United States)

Bhattarai, Yogesh; Schmidt, Bradley A; Linden, David R; Larson, Eric D; Grover, Madhusudan; Beyder, Arthur; Farrugia, Gianrico; Kashyap, Purna C

2017-07-01

Serotonin [5-hydroxytryptamine (5-HT)], an important neurotransmitter and a paracrine messenger in the gastrointestinal tract, regulates intestinal secretion by its action primarily on 5-HT 3 and 5-HT 4 receptors. Recent studies highlight the role of gut microbiota in 5-HT biosynthesis. In this study, we determine whether human-derived gut microbiota affects host secretory response to 5-HT and 5-HT receptor expression. We used proximal colonic mucosa-submucosa preparation from age-matched Swiss Webster germ-free (GF) and humanized (HM; ex-GF colonized with human gut microbiota) mice. 5-HT evoked a significantly greater increase in short-circuit current (Δ I sc ) in GF compared with HM mice. Additionally, 5-HT 3 receptor mRNA and protein expression was significantly higher in GF compared with HM mice. Ondansetron, a 5-HT 3 receptor antagonist, inhibited 5-HT-evoked Δ I sc in GF mice but not in HM mice. Furthermore, a 5-HT 3 receptor-selective agonist, 2-methyl-5-hydroxytryptamine hydrochloride, evoked a significantly higher Δ I sc in GF compared with HM mice. Immunohistochemistry in 5-HT 3A -green fluorescent protein mice localized 5-HT 3 receptor expression to enterochromaffin cells in addition to nerve fibers. The significant difference in 5-HT-evoked Δ I sc between GF and HM mice persisted in the presence of tetrodotoxin (TTX) but was lost after ondansetron application in the presence of TTX. Application of acetate (10 mM) significantly lowered 5-HT 3 receptor mRNA in GF mouse colonoids. We conclude that host secretory response to 5-HT may be modulated by gut microbiota regulation of 5-HT 3 receptor expression via acetate production. Epithelial 5-HT 3 receptor may function as a mediator of gut microbiota-driven change in intestinal secretion. NEW & NOTEWORTHY We found that gut microbiota alters serotonin (5-HT)-evoked intestinal secretion in a 5-HT 3 receptor-dependent mechanism and gut microbiota metabolite acetate alters 5-HT 3 receptor expression in

In vitro fermentation behaviors of fucosylated chondroitin sulfate from Pearsonothuria graeffei by human gut microflora.

Science.gov (United States)

Wei, Chao-Yang; Liao, Ning-Bo; Zhang, Yu; Ye, Xing-Qian; Li, Shan; Hu, Ya-Qin; Liu, Dong-Hong; Linhardt, Robert J; Wang, Xin; Chen, Shi-Guo

2017-09-01

A fucosylated chondroitin sulfate (FCS-pg) with highly repeated structure from Pearsonothuria graeffei was subjected to a in vitro fermentation model to investigate its fermentability and effects on human gut microflora. High performance liquid chromatography (HPLC) measurement found FCS-pg can be fermented to short chain fatty acids (SCFAs) by gut microflora from partial human fecal samples. 16S rRNA gene-based polymerase chain reaction-based denaturing gradient gel electrophoresis (PCR-DGGE) profiling and real-time quantitative PCR analysis showed that FCS-pg mainly increased the proportions of Clostridium cluster XI, Bacteriodes prevotella group, Bifidobacterium genus, Clostridium cluster I and Clostridium cluster XIVab, whereas the numbers of the Enterobacteriaceae and Lactobacillus decreased. These results indicated that FCS-pg was mainly fermented by Bacteroides, Bifidobacterium and Clostridium. It increased the content of probiotics bacteria in achieving health-enhancing effect, was slightly different than most sulfated polysaccharides from marine animals. The current study provides useful new information on the mechanism of absorption and functional activity on FCS-pg within the gastrointestinal tract of the human body. Copyright © 2017. Published by Elsevier B.V.

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

Evaluating variation in human gut microbiota profiles due to DNA extraction method and inter-subject differences.

Science.gov (United States)

Wagner Mackenzie, Brett; Waite, David W; Taylor, Michael W

2015-01-01

The human gut contains dense and diverse microbial communities which have profound influences on human health. Gaining meaningful insights into these communities requires provision of high quality microbial nucleic acids from human fecal samples, as well as an understanding of the sources of variation and their impacts on the experimental model. We present here a systematic analysis of commonly used microbial DNA extraction methods, and identify significant sources of variation. Five extraction methods (Human Microbiome Project protocol, MoBio PowerSoil DNA Isolation Kit, QIAamp DNA Stool Mini Kit, ZR Fecal DNA MiniPrep, phenol:chloroform-based DNA isolation) were evaluated based on the following criteria: DNA yield, quality and integrity, and microbial community structure based on Illumina amplicon sequencing of the V4 region of bacterial and archaeal 16S rRNA genes. Our results indicate that the largest portion of variation within the model was attributed to differences between subjects (biological variation), with a smaller proportion of variation associated with DNA extraction method (technical variation) and intra-subject variation. A comprehensive understanding of the potential impact of technical variation on the human gut microbiota will help limit preventable bias, enabling more accurate diversity estimates.

Evaluating variation in human gut microbiota profiles due to DNA extraction method and inter-subject differences

Directory of Open Access Journals (Sweden)

Brett eWagner Mackenzie

2015-02-01

Full Text Available The human gut contains dense and diverse microbial communities which have profound influences on human health. Gaining meaningful insights into these communities requires provision of high quality microbial nucleic acids from human fecal samples, as well as an understanding of the sources of variation and their impacts on the experimental model. We present here a systematic analysis of commonly used microbial DNA extraction methods, and identify significant sources of variation. Five extraction methods (Human Microbiome Project protocol, MoBio PowerSoil DNA Isolation Kit, QIAamp DNA Stool Mini Kit, ZR Fecal DNA MiniPrep, phenol:chloroform-based DNA isolation were evaluated based on the following criteria: DNA yield, quality and integrity, and microbial community structure based on Illumina amplicon sequencing of the V4 region of bacterial and archaeal 16S rRNA genes. Our results indicate that the largest portion of variation within the model was attributed to differences between subjects (biological variation, with a smaller proportion of variation associated with DNA extraction method (technical variation and intra-subject variation. A comprehensive understanding of the potential impact of technical variation on the human gut microbiota will help limit preventable bias, enabling more accurate diversity estimates.

The Influence of Social Conditions Across the Life Course on the Human Gut Microbiota: A Pilot Project With the Wisconsin Longitudinal Study.

Science.gov (United States)

Herd, Pamela; Schaeffer, Nora Cate; DiLoreto, Kerryann; Jacques, Karen; Stevenson, John; Rey, Federico; Roan, Carol

2017-12-15

To test the feasibility of collecting and integrating data on the gut microbiome into one of the most comprehensive longitudinal studies of aging and health, the Wisconsin Longitudinal Study (WLS). The long-term goal of this integration is to clarify the contribution of social conditions in shaping the composition of the gut microbiota late in life. Research on the microbiome, which is considered to be of parallel importance to human health as the human genome, has been hindered by human studies with nonrandomly selected samples and with limited data on social conditions over the life course. No existing population-based longitudinal study had collected fecal specimens. Consequently, we created an in-person protocol to collect stool specimens from a subgroup of WLS participants. We collected 429 stool specimens, yielding a 74% response rate and one of the largest human samples to date. The addition of data on the gut microbiome to the WLS-and to other population based longitudinal studies of aging-is feasible, under the right conditions, and can generate innovative research on the relationship between social conditions and the gut microbiome. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Country-specific antibiotic use practices impact the human gut resistome

DEFF Research Database (Denmark)

Forslund, Kristoffer; Sunagawa, Shinichi; Kultima, Jens Roat

2013-01-01

Despite increasing concerns over inappropriate use of antibiotics in medicine and food production, population-level resistance transfer into the human gut microbiota has not been demonstrated beyond individual case studies. To determine the "antibiotic resistance potential" for entire microbial...... in animals and for antibiotics that have been available longer. Resistance genes are also more abundant in samples from Spain, Italy, and France than from Denmark, the United States, or Japan. Where comparable country-level data on antibiotic use in both humans and animals are available, differences...... communities, we employ metagenomic data and quantify the totality of known resistance genes in each community (its resistome) for 68 classes and subclasses of antibiotics. In 252 fecal metagenomes from three countries, we show that the most abundant resistance determinants are those for antibiotics also used...

Metabolic Interaction of Helicobacter pylori Infection and Gut Microbiota

Directory of Open Access Journals (Sweden)

Yao-Jong Yang

2016-02-01

Full Text Available As a barrier, gut commensal microbiota can protect against potential pathogenic microbes in the gastrointestinal tract. Crosstalk between gut microbes and immune cells promotes human intestinal homeostasis. Dysbiosis of gut microbiota has been implicated in the development of many human metabolic disorders like obesity, hepatic steatohepatitis, and insulin resistance in type 2 diabetes (T2D. Certain microbes, such as butyrate-producing bacteria, are lower in T2D patients. The transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome, but the exact pathogenesis remains unclear. H. pylori in the human stomach cause chronic gastritis, peptic ulcers, and gastric cancers. H. pylori infection also induces insulin resistance and has been defined as a predisposing factor to T2D development. Gastric and fecal microbiota may have been changed in H. pylori-infected persons and mice to promote gastric inflammation and specific diseases. However, the interaction of H. pylori and gut microbiota in regulating host metabolism also remains unknown. Further studies aim to identify the H. pylori-microbiota-host metabolism axis and to test if H. pylori eradication or modification of gut microbiota can improve the control of human metabolic disorders.

Dietary Fiber and the Human Gut Microbiota: Application of Evidence Mapping Methodology

Directory of Open Access Journals (Sweden)

Caleigh M. Sawicki

2017-02-01

Full Text Available Interest is rapidly growing around the role of the human gut microbiota in facilitating beneficial health effects associated with consumption of dietary fiber. An evidence map of current research activity in this area was created using a newly developed database of dietary fiber intervention studies in humans to identify studies with the following broad outcomes: (1 modulation of colonic microflora; and/or (2 colonic fermentation/short-chain fatty acid concentration. Study design characteristics, fiber exposures, and outcome categories were summarized. A sub-analysis described oligosaccharides and bacterial composition in greater detail. One hundred eighty-eight relevant studies were identified. The fiber categories represented by the most studies were oligosaccharides (20%, resistant starch (16%, and chemically synthesized fibers (15%. Short-chain fatty acid concentration (47% and bacterial composition (88% were the most frequently studied outcomes. Whole-diet interventions, measures of bacterial activity, and studies in metabolically at-risk subjects were identified as potential gaps in the evidence. This evidence map efficiently captured the variability in characteristics of expanding research on dietary fiber, gut microbiota, and physiological health benefits, and identified areas that may benefit from further research. We hope that this evidence map will provide a resource for researchers to direct new intervention studies and meta-analyses.

Two new xylanases with different substrate specificities from the human gut bacterium Bacteroides intestinalis DSM 17393.

Science.gov (United States)

Hong, Pei-Ying; Iakiviak, Michael; Dodd, Dylan; Zhang, Meiling; Mackie, Roderick I; Cann, Isaac

2014-04-01

Xylan is an abundant plant cell wall polysaccharide and is a dominant component of dietary fiber. Bacteria in the distal human gastrointestinal tract produce xylanase enzymes to initiate the degradation of this complex heteropolymer. These xylanases typically derive from glycoside hydrolase (GH) families 10 and 11; however, analysis of the genome sequence of the xylan-degrading human gut bacterium Bacteroides intestinalis DSM 17393 revealed the presence of two putative GH8 xylanases. In the current study, we demonstrate that the two genes encode enzymes that differ in activity. The xyn8A gene encodes an endoxylanase (Xyn8A), and rex8A encodes a reducing-end xylose-releasing exo-oligoxylanase (Rex8A). Xyn8A hydrolyzed both xylopentaose (X5) and xylohexaose (X6) to a mixture of xylobiose (X2) and xylotriose (X3), while Rex8A hydrolyzed X3 through X6 to a mixture of xylose (X1) and X2. Moreover, rex8A is located downstream of a GH3 gene (xyl3A) that was demonstrated to exhibit β-xylosidase activity and would be able to further hydrolyze X2 to X1. Mutational analyses of putative active site residues of both Xyn8A and Rex8A confirm their importance in catalysis by these enzymes. Recent genome sequences of gut bacteria reveal an increase in GH8 Rex enzymes, especially among the Bacteroidetes, indicating that these genes contribute to xylan utilization in the human gut.

Two New Xylanases with Different Substrate Specificities from the Human Gut Bacterium Bacteroides intestinalis DSM 17393

KAUST Repository

Hong, Pei-Ying

2014-01-24

Xylan is an abundant plant cell wall polysaccharide and is a dominant component of dietary fiber. Bacteria in the distal human gastrointestinal tract produce xylanase enzymes to initiate the degradation of this complex heteropolymer. These xylanases typically derive from glycoside hydrolase (GH) families 10 and 11; however, analysis of the genome sequence of the xylan-degrading human gut bacterium Bacteroides intestinalis DSM 17393 revealed the presence of two putative GH8 xylanases. In the current study, we demonstrate that the two genes encode enzymes that differ in activity. The xyn8A gene encodes an endoxylanase (Xyn8A), and rex8A encodes a reducing-end xylose-releasing exo-oligoxylanase (Rex8A). Xyn8A hydrolyzed both xylopentaose (X5) and xylohexaose (X6) to a mixture of xylobiose (X2) and xylotriose (X3), while Rex8A hydrolyzed X3 through X6 to a mixture of xylose (X1) and X2. Moreover, rex8A is located downstream of a GH3 gene (xyl3A) that was demonstrated to exhibit β-xylosidase activity and would be able to further hydrolyze X2 to X1. Mutational analyses of putative active site residues of both Xyn8A and Rex8A confirm their importance in catalysis by these enzymes. Recent genome sequences of gut bacteria reveal an increase in GH8 Rex enzymes, especially among the Bacteroidetes, indicating that these genes contribute to xylan utilization in the human gut.

Two New Xylanases with Different Substrate Specificities from the Human Gut Bacterium Bacteroides intestinalis DSM 17393

KAUST Repository

Hong, Pei-Ying; Iakiviak, M.; Dodd, D.; Zhang, M.; Mackie, R. I.; Cann, I.

2014-01-01

Xylan is an abundant plant cell wall polysaccharide and is a dominant component of dietary fiber. Bacteria in the distal human gastrointestinal tract produce xylanase enzymes to initiate the degradation of this complex heteropolymer. These xylanases typically derive from glycoside hydrolase (GH) families 10 and 11; however, analysis of the genome sequence of the xylan-degrading human gut bacterium Bacteroides intestinalis DSM 17393 revealed the presence of two putative GH8 xylanases. In the current study, we demonstrate that the two genes encode enzymes that differ in activity. The xyn8A gene encodes an endoxylanase (Xyn8A), and rex8A encodes a reducing-end xylose-releasing exo-oligoxylanase (Rex8A). Xyn8A hydrolyzed both xylopentaose (X5) and xylohexaose (X6) to a mixture of xylobiose (X2) and xylotriose (X3), while Rex8A hydrolyzed X3 through X6 to a mixture of xylose (X1) and X2. Moreover, rex8A is located downstream of a GH3 gene (xyl3A) that was demonstrated to exhibit β-xylosidase activity and would be able to further hydrolyze X2 to X1. Mutational analyses of putative active site residues of both Xyn8A and Rex8A confirm their importance in catalysis by these enzymes. Recent genome sequences of gut bacteria reveal an increase in GH8 Rex enzymes, especially among the Bacteroidetes, indicating that these genes contribute to xylan utilization in the human gut.

Habitual dietary fibre intake influences gut microbiota response to an inulin-type fructan prebiotic:a randomised, double-blind, placebo-controlled, cross-over, human intervention study

OpenAIRE

Healey, Genelle; Murphy, Rinki; Butts, Chrissie; Brough, Louise; Whelan, Kevin; Coad, Jane

2018-01-01

Dysbiotic gut microbiota have been implicated in human disease. Diet-based therapeutic strategies have been used to manipulate the gut microbiota towards a more favourable profile. However, it has been demonstrated that large inter-individual variability exists in gut microbiota response to a dietary intervention. The primary objective of this study was to investigate whether habitually low dietary fibre (LDF) v. high dietary fibre (HDF) intakes influence gut microbiota response to an inulin-...

Human gut endogenous proteins as a potential source of angiotensin-I-converting enzyme (ACE-I)-, renin inhibitory and antioxidant peptides.

Science.gov (United States)

Dave, Lakshmi A; Hayes, Maria; Montoya, Carlos A; Rutherfurd, Shane M; Moughan, Paul J

2016-02-01

It is well known that endogenous bioactive proteins and peptides play a substantial role in the body's first line of immunological defence, immune-regulation and normal body functioning. Further, the peptides derived from the luminal digestion of proteins are also important for body function. For example, within the peptide database BIOPEP (http://www.uwm.edu.pl/biochemia/index.php/en/biopep) 12 endogenous antimicrobial and 64 angiotensin-I-converting enzyme (ACE-I) inhibitory peptides derived from human milk and plasma proteins are listed. The antimicrobial peptide database (http://aps.unmc.edu/AP/main.php) lists over 111 human host-defence peptides. Several endogenous proteins are secreted in the gut and are subject to the same gastrointestinal digestion processes as food proteins derived from the diet. The human gut endogenous proteins (GEP) include mucins, serum albumin, digestive enzymes, hormones, and proteins from sloughed off epithelial cells and gut microbiota, and numerous other secreted proteins. To date, much work has been carried out regarding the health altering effects of food-derived bioactive peptides but little attention has been paid to the possibility that GEP may also be a source of bioactive peptides. In this review, we discuss the potential of GEP to constitute a gut cryptome from which bioactive peptides such as ACE-I inhibitory, renin inhibitory and antioxidant peptides may be derived. Copyright © 2015 Elsevier Inc. All rights reserved.

Antimicrobial activity of actinobacteria isolated from the guts of subterranean termites

Science.gov (United States)

Rachel Arango; C. M. Carlson; C. R. Currie; B. R. McDonald; A. J. Book; Frederick Green; K. F. Raffa; N.K. Lebow

2016-01-01

Subterranean termites need to minimize potentially pathogenic and competitive fungi in their environment in order to maintain colony health. We examined the ability of Actinobacteria isolated from termite guts in suppressing microorganisms commonly encountered in a subterranean environment. Guts from two subterranean termite species, Reticulitermes flavipes...

MicroRNA-orchestrated pathophysiologic control in gut homeostasis and inflammation.

Science.gov (United States)

Lee, Juneyoung; Park, Eun Jeong; Kiyono, Hiroshi

2016-05-01

The intestine represents the largest and most elaborate immune system organ, in which dynamic and reciprocal interplay among numerous immune and epithelial cells, commensal microbiota, and external antigens contributes to establishing both homeostatic and pathologic conditions. The mechanisms that sustain gut homeostasis are pivotal in maintaining gut health in the harsh environment of the gut lumen. Intestinal epithelial cells are critical players in creating the mucosal platform for interplay between host immune cells and luminal stress inducers. Thus, knowledge of the epithelial interface between immune cells and the luminal environment is a prerequisite for a better understanding of gut homeostasis and pathophysiologies such as inflammation. In this review, we explore the importance of the epithelium in limiting or promoting gut inflammation (e.g., inflammatory bowel disease). We also introduce recent findings on how small RNAs such as microRNAs orchestrate pathophysiologic gene regulation. [BMB Reports 2016; 49(5): 263-269].

Modulation of Gut Microbiota in Pathological States

DEFF Research Database (Denmark)

Wang, Yulan; Wang, Baohong; Wu, Junfang

2017-01-01

The human microbiota is an aggregate of microorganisms residing in the human body, mostly in the gastrointestinal tract (GIT). Our gut microbiota evolves with us and plays a pivotal role in human health and disease. In recent years, the microbiota has gained increasing attention due to its impact...... on host metabolism, physiology, and immune system development, but also because the perturbation of the microbiota may result in a number of diseases. The gut microbiota may be linked to malignancies such as gastric cancer and colorectal cancer. It may also be linked to disorders such as nonalcoholic...... fatty liver disease (NAFLD); obesity and diabetes, which are characterized as “lifestyle diseases” of the industrialized world; coronary heart disease; and neurological disorders. Although the revolution in molecular technologies has provided us with the necessary tools to study the gut microbiota more...

Development of Human Breast Milk Microbiota-Associated Mice as a Method to Identify Breast Milk Bacteria Capable of Colonizing Gut.

Science.gov (United States)

Wang, Xiaoxin; Lu, Huifang; Feng, Zhou; Cao, Jie; Fang, Chao; Xu, Xianming; Zhao, Liping; Shen, Jian

2017-01-01

Human breast milk is recognized as one of multiple important sources of commensal bacteria for infant gut. Previous studies searched for the bacterial strains shared between breast milk and infant feces by isolating bacteria and performing strain-level bacterial genotyping, but only limited number of milk bacteria were identified to colonize infant gut, including bacteria from Bifidobacterium , Staphylococcus , Lactobacillus , and Escherichia / Shigella . Here, to identify the breast milk bacteria capable of colonizing gut without the interference of bacteria of origins other than the milk or the necessity to analyze infant feces, normal chow-fed germ-free mice were orally inoculated with the breast milk collected from a mother 2 days after vaginal delivery. According to 16S rRNA gene-based denaturant gradient gel electrophoresis and Illumina sequencing, bacteria at >1% abundance in the milk inoculum were only Streptococcus (56.0%) and Staphylococcus (37.4%), but in the feces of recipient mice were Streptococcus (80.3 ± 2.3%), Corynebacterium (10.0 ± 2.6 %), Staphylococcus (7.6 ± 1.6%), and Propionibacterium (2.1 ± 0.5%) that were previously shown as dominant bacterial genera in the meconium of C-section-delivered human babies; the abundance of anaerobic gut-associated bacteria, Faecalibacterium , Prevotella , Roseburia , Ruminococcus , and Bacteroides , was 0.01-1% in the milk inoculum and 0.003-0.01% in mouse feces; the abundance of Bifidobacterium spp. was below the detection limit of Illumina sequencing in the milk but at 0.003-0.01% in mouse feces. The human breast milk microbiota-associated mouse model may be used to identify additional breast milk bacteria that potentially colonize infant gut.

Prebiotic galactooligosaccharides activate mucin and pectic galactan utilization pathways in the human gut symbiont Bacteroides thetaiotaomicron

NARCIS (Netherlands)

Lammerts van Bueren, Alicia; Mulder, Marieke; Leeuwen, Sander van; Dijkhuizen, Lubbert

2017-01-01

Galactooligosaccharides (GOS) are prebiotic carbohydrates that impart changes in the gut bacterial composition of formula-fed infants to more closely resemble that of breast-fed infants. Consuming human milk oligosaccharides (HMOs) provides specific bacterial strains with an advantage for colonizing

The Extended Nutrigenomics – Understanding the Interplay between the Genomes of Food, Gut Microbes and Human Host

Directory of Open Access Journals (Sweden)

Martin eKussmann

2011-05-01

Full Text Available Comprehensive investigation of nutritional health effects at molecular level requires understanding the interplay between three genomes, the food, the gut microbial and the human host genome. Food genomes are researched for exploitation of macro- and micronutrients as well as bioactives, with the genes coding for bioactive proteins and peptides being of central interest. The human gut microbiota encompasses a complex intestinal ecosystem with profound impact on host metabolism. It is studied at genomic, proteomic and metabolomic level. Humans are characterized at the level of: genetic predisposition and variability in terms of dietary response and direction of health trajectories; epigenetic, metabolic programming at certain life stages with health consequences later in life and for subsequent generations; and acute genomic expression as a holistic response to diet, monitored at gene transcript, protein and metabolite level.Modern nutrition science explores health aspects of bioactive food components, thereby promoting health, preventing or delaying the onset of disease, optimizing performance and assessing benefits and risks. Personalized nutrition means adapting food to individual needs, depending on the human host’s life stage, -style and -situation. Traditionally, nutrigenomics and nutri(epigenetics have been seen as the key sciences to understand human variability in preferences and requirements for diet as well as responses to nutrition. This article puts the three nutrition and health-relevant genomes into perspective, i.e. the food, the gut microbial and the human host’s genome, and calls for an extended nutrigenomics approach to build the future tools for personalized nutrition, health maintenance and disease prevention. We discuss examples of these genomes, proteomes, transcriptomes and metabolomes under the overarching term genomics that covers all Omics rather than the sole study of DNA and RNA.

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.

Fit reduced GUTS models online: From theory to practice.

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Baudrot, Virgile; Veber, Philippe; Gence, Guillaume; Charles, Sandrine

2018-05-20

Mechanistic modeling approaches, such as the toxicokinetic-toxicodynamic (TKTD) framework, are promoted by international institutions such as the European Food Safety Authority and the Organization for Economic Cooperation and Development to assess the environmental risk of chemical products generated by human activities. TKTD models can encompass a large set of mechanisms describing the kinetics of compounds inside organisms (e.g., uptake and elimination) and their effect at the level of individuals (e.g., damage accrual, recovery, and death mechanism). Compared to classical dose-response models, TKTD approaches have many advantages, including accounting for temporal aspects of exposure and toxicity, considering data points all along the experiment and not only at the end, and making predictions for untested situations as realistic exposure scenarios. Among TKTD models, the general unified threshold model of survival (GUTS) is within the most recent and innovative framework but is still underused in practice, especially by risk assessors, because specialist programming and statistical skills are necessary to run it. Making GUTS models easier to use through a new module freely available from the web platform MOSAIC (standing for MOdeling and StAtistical tools for ecotoxIClogy) should promote GUTS operability in support of the daily work of environmental risk assessors. This paper presents the main features of MOSAIC_GUTS: uploading of the experimental data, GUTS fitting analysis, and LCx estimates with their uncertainty. These features will be exemplified from literature data. Integr Environ Assess Manag 2018;00:000-000. © 2018 SETAC. © 2018 SETAC.

Effects of almond and pistachio consumption on gut microbiota composition in a randomised cross-over human feeding study.

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Ukhanova, Maria; Wang, Xiaoyu; Baer, David J; Novotny, Janet A; Fredborg, Marlene; Mai, Volker

2014-06-28

The modification of microbiota composition to a 'beneficial' one is a promising approach for improving intestinal as well as overall health. Natural fibres and phytochemicals that reach the proximal colon, such as those present in various nuts, provide substrates for the maintenance of healthy and diverse microbiota. The effects of increased consumption of specific nuts, which are rich in fibre as well as various phytonutrients, on human gut microbiota composition have not been investigated to date. The objective of the present study was to determine the effects of almond and pistachio consumption on human gut microbiota composition. We characterised microbiota in faecal samples collected from volunteers in two separate randomised, controlled, cross-over feeding studies (n 18 for the almond feeding study and n 16 for the pistachio feeding study) with 0, 1·5 or 3 servings/d of the respective nuts for 18 d. Gut microbiota composition was analysed using a 16S rRNA-based approach for bacteria and an internal transcribed spacer region sequencing approach for fungi. The 16S rRNA sequence analysis of 528 028 sequence reads, retained after removing low-quality and short-length reads, revealed various operational taxonomic units that appeared to be affected by nut consumption. The effect of pistachio consumption on gut microbiota composition was much stronger than that of almond consumption and included an increase in the number of potentially beneficial butyrate-producing bacteria. Although the numbers of bifidobacteria were not affected by the consumption of either nut, pistachio consumption appeared to decrease the number of lactic acid bacteria (Ppistachios appears to be an effective means of modifying gut microbiota composition.

First Foods and Gut Microbes

DEFF Research Database (Denmark)

Laursen, Martin Frederik; Bahl, Martin Iain; Michaelsen, Kim F.

2017-01-01

The establishment of the human gut microbiota in early life has been associated with later health and disease. During the 1st months after birth, the microbial composition in the gut is known to be affected by the mode of delivery, use of antibiotics, geographical location and type of feeding...... of this window is currently debated, but it likely coincides with the complementary feeding period, marking the gradual transition from milk- based infant feeding to family diet usually occurring between 6 and 24 months. Furthermore, the 'first 1000 days,' i.e., the period from conception until age 2 years...... microbiota development. This perspective paper summarizes the currently very few studies addressing the effects of complementary diet on gut microbiota, and highlights the recent finding that transition to family foods greatly impacts the development of gut microbial diversity. Further, we discuss potential...

Genomics: A gut prediction

NARCIS (Netherlands)

Vos, de W.M.; Nieuwdorp, M.

2013-01-01

Microbial cells make up the majority of cells in the human body, and most of these reside in the intestinal tract. Researchers have long recognized that some intestinal microorganisms are associated with health, but the beneficial impact of most of the gut's microbes on human metabolism has been

Role of Gut Microbiota in the Aetiology of Obesity: Proposed Mechanisms and Review of the Literature

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Gerasimidis, Konstantinos; Edwards, Christine Ann; Shaikh, M. Guftar

2016-01-01

The aetiology of obesity has been attributed to several factors (environmental, dietary, lifestyle, host, and genetic factors); however none of these fully explain the increase in the prevalence of obesity worldwide. Gut microbiota located at the interface of host and environment in the gut are a new area of research being explored to explain the excess accumulation of energy in obese individuals and may be a potential target for therapeutic manipulation to reduce host energy storage. Several mechanisms have been suggested to explain the role of gut microbiota in the aetiology of obesity such as short chain fatty acid production, stimulation of hormones, chronic low-grade inflammation, lipoprotein and bile acid metabolism, and increased endocannabinoid receptor system tone. However, evidence from animal and human studies clearly indicates controversies in determining the cause or effect relationship between the gut microbiota and obesity. Metagenomics based studies indicate that functionality rather than the composition of gut microbiota may be important. Further mechanistic studies controlling for environmental and epigenetic factors are therefore required to help unravel obesity pathogenesis. PMID:27703805

Faecalibacterium Gut Colonization Is Accelerated by Presence of Older Siblings

DEFF Research Database (Denmark)

Laursen, Martin Frederik; Laursen, Rikke Pilmann; Larnkjær, Anni

2017-01-01

Faecalibacterium prausnitzii is a highly abundant human gut microbe in healthy individuals, but it is present at reduced levels in individuals with gastrointestinal inflammatory diseases. It has therefore been suggested to constitute a marker of a healthy gut and is associated with anti......-inflammatory properties. However, factors affecting the colonization of F. prausnitzii in the human gut during early life are very poorly understood. By analysis of 16S rRNA amplicon sequencing data from three separate infant study populations, we determined the colonization dynamics of Faecalibacterium and factors...... affecting its establishment in the gut. We found that in particular, the presence of older siblings was consistently associated with Faecalibacterium gut colonization during late infancy and conclude that acquisition of Faecalibacterium is very likely to be accelerated through transfer between siblings...

Gut microbiome of the Hadza hunter-gatherers.

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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.

Influence of gut microbiota on neuropsychiatric disorders.

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Cenit, María Carmen; Sanz, Yolanda; Codoñer-Franch, Pilar

2017-08-14

The last decade has witnessed a growing appreciation of the fundamental role played by an early assembly of a diverse and balanced gut microbiota and its subsequent maintenance for future health of the host. Gut microbiota is currently viewed as a key regulator of a fluent bidirectional dialogue between the gut and the brain (gut-brain axis). A number of preclinical studies have suggested that the microbiota and its genome (microbiome) may play a key role in neurodevelopmental and neurodegenerative disorders. Furthermore, alterations in the gut microbiota composition in humans have also been linked to a variety of neuropsychiatric conditions, including depression, autism and Parkinson's disease. However, it is not yet clear whether these changes in the microbiome are causally related to such diseases or are secondary effects thereof. In this respect, recent studies in animals have indicated that gut microbiota transplantation can transfer a behavioral phenotype, suggesting that the gut microbiota may be a modifiable factor modulating the development or pathogenesis of neuropsychiatric conditions. Further studies are warranted to establish whether or not the findings of preclinical animal experiments can be generalized to humans. Moreover, although different communication routes between the microbiota and brain have been identified, further studies must elucidate all the underlying mechanisms involved. Such research is expected to contribute to the design of strategies to modulate the gut microbiota and its functions with a view to improving mental health, and thus provide opportunities to improve the management of psychiatric diseases. Here, we review the evidence supporting a role of the gut microbiota in neuropsychiatric disorders and the state of the art regarding the mechanisms underlying its contribution to mental illness and health. We also consider the stages of life where the gut microbiota is more susceptible to the effects of environmental stressors, and

Genome-Wide Association Studies of the Human Gut Microbiota.

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Emily R Davenport

Full Text Available The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both. These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%. For example, we identified an association between a taxon known to affect obesity (genus Akkermansia and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10-7. Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut.

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

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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.

The influence of Staphylococcus aureus on gut microbial ecology in an in vitro continuous culture human colonic model system.

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Sannasiddappa, Thippeswamy H; Costabile, Adele; Gibson, Glenn R; Clarke, Simon R

2011-01-01

An anaerobic three-stage continuous culture model of the human colon (gut model), which represent different anatomical areas of the large intestine, was used to study the effect of S. aureus infection of the gut on the resident faecal microbiota. Studies on the development of the microbiota in the three vessels were performed and bacteria identified by culture independent fluorescence in situ hybridization (FISH). Furthermore, short chain fatty acids (SCFA), as principal end products of gut bacterial metabolism, were measured along with a quantitative assessment of the predominant microbiota. During steady state conditions, numbers of S. aureus cells stabilised until they were washed out, but populations of indigenous bacteria were transiently altered; thus S. aureus was able to compromise colonisation resistance by the colonic microbiota. Furthermore, the concentration of butyric acid in the vessel representing the proximal colon was significantly decreased by infection. Thus infection by S. aureus appears to be able to alter the overall structure of the human colonic microbiota and the microbial metabolic profiles. This work provides an initial in vitro model to analyse interactions with pathogens.

Comparative study on the in vitro effects of Pseudomonas aeruginosa and seaweed alginates on human gut microbiota.

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Shaofeng Bai

Full Text Available Alginates pertain to organic polysaccharides that have been extensively used in food- and medicine-related industries. The present study obtained alginates from an alginate overproducing Pseudomonas aeruginosa PAO1 mutant by screening transposon mutagenesis libraries. The interaction between bacterial and seaweed alginates and gut microbiota were further studied by using an in vitro batch fermentation system. Thin-layer chromatography (TLC analysis indicated that both bacterial and seaweed alginates can be completely degraded by fecal bacteria isolated from study volunteers, indicating that a minor structural difference between bacterial and seaweed alginates (O-acetylation and lack of G-G blocks didn't affect the digestion of alginates by human microbiota. Although, the digestion of bacterial and seaweed alginates was attributed to different Bacteroides xylanisolvens strains, they harbored similar alginate lyase genes. Genus Bacteroides with alginate-degrading capability were enriched in growth medium containing bacterial or seaweed alginates after in vitro fermentation. Short-chain fatty acid (SCFA production in both bacterial and seaweed alginates was also comparable, but was significantly higher than the same medium using starch. In summary, the present study has isolated an alginate-overproducing P. aeruginosa mutant strain. Both seaweed and bacterial alginates were degraded by human gut microbiota, and their regulatory function on gut microbiota was similar.

Comparative study on the in vitro effects of Pseudomonas aeruginosa and seaweed alginates on human gut microbiota.

Science.gov (United States)

Bai, Shaofeng; Chen, Huahai; Zhu, Liying; Liu, Wei; Yu, Hongwei D; Wang, Xin; Yin, Yeshi

2017-01-01

Alginates pertain to organic polysaccharides that have been extensively used in food- and medicine-related industries. The present study obtained alginates from an alginate overproducing Pseudomonas aeruginosa PAO1 mutant by screening transposon mutagenesis libraries. The interaction between bacterial and seaweed alginates and gut microbiota were further studied by using an in vitro batch fermentation system. Thin-layer chromatography (TLC) analysis indicated that both bacterial and seaweed alginates can be completely degraded by fecal bacteria isolated from study volunteers, indicating that a minor structural difference between bacterial and seaweed alginates (O-acetylation and lack of G-G blocks) didn't affect the digestion of alginates by human microbiota. Although, the digestion of bacterial and seaweed alginates was attributed to different Bacteroides xylanisolvens strains, they harbored similar alginate lyase genes. Genus Bacteroides with alginate-degrading capability were enriched in growth medium containing bacterial or seaweed alginates after in vitro fermentation. Short-chain fatty acid (SCFA) production in both bacterial and seaweed alginates was also comparable, but was significantly higher than the same medium using starch. In summary, the present study has isolated an alginate-overproducing P. aeruginosa mutant strain. Both seaweed and bacterial alginates were degraded by human gut microbiota, and their regulatory function on gut microbiota was similar.

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

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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...

Type VI secretion systems of human gut Bacteroidales segregate into three genetic architectures, two of which are contained on mobile genetic elements.

Science.gov (United States)

Coyne, Michael J; Roelofs, Kevin G; Comstock, Laurie E

2016-01-15

Type VI secretion systems (T6SSs) are contact-dependent antagonistic systems employed by Gram negative bacteria to intoxicate other bacteria or eukaryotic cells. T6SSs were recently discovered in a few Bacteroidetes strains, thereby extending the presence of these systems beyond Proteobacteria. The present study was designed to analyze in a global nature the diversity, abundance, and properties of T6SSs in the Bacteroidales, the most predominant Gram negative bacterial order of the human gut. By performing extensive bioinformatics analyses and creating hidden Markov models for Bacteroidales Tss proteins, we identified 130 T6SS loci in 205 human gut Bacteroidales genomes. Of the 13 core T6SS proteins of Proteobacteria, human gut Bacteroidales T6SS loci encode orthologs of nine, and an additional five other core proteins not present in Proteobacterial T6SSs. The Bacteroidales T6SS loci segregate into three distinct genetic architectures with extensive DNA identity between loci of a given genetic architecture. We found that divergent DNA regions of a genetic architecture encode numerous types of effector and immunity proteins and likely include new classes of these proteins. TheT6SS loci of genetic architecture 1 are contained on highly similar integrative conjugative elements (ICEs), as are the T6SS loci of genetic architecture 2, whereas the T6SS loci of genetic architecture 3 are not and are confined to Bacteroides fragilis. Using collections of co-resident Bacteroidales strains from human subjects, we provide evidence for the transfer of genetic architecture 1 T6SS loci among co-resident Bacteroidales species in the human gut. However, we also found that established ecosystems can harbor strains with distinct T6SS of all genetic architectures. This is the first study to comprehensively analyze of the presence and diversity of T6SS loci within an order of bacteria and to analyze T6SSs of bacteria from a natural community. These studies demonstrate that more than

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.

Microbiota-Brain-Gut Axis and Neurodegenerative Diseases.

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Quigley, Eamonn M M

2017-10-17

The purposes of this review were as follows: first, to provide an overview of the gut microbiota and its interactions with the gut and the central nervous system (the microbiota-gut-brain axis) in health, second, to review the relevance of this axis to the pathogenesis of neurodegenerative diseases, such as Parkinson's disease, and, finally, to assess the potential for microbiota-targeted therapies. Work on animal models has established the microbiota-gut-brain axis as a real phenomenon; to date, the evidence for its operation in man has been limited and has been confronted by considerable logistical challenges. Animal and translational models have incriminated a disturbed gut microbiota in a number of CNS disorders, including Parkinson's disease; data from human studies is scanty. While a theoretical basis can be developed for the use of microbiota-directed therapies in neurodegenerative disorders, support is yet to come from high-quality clinical trials. In theory, a role for the microbiota-gut-brain axis is highly plausible; clinical confirmation is awaited.

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

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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

Gut microbiome and its role in cardiovascular diseases.

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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.

The Gut Microbiota of Marine Fish

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Egerton, Sian; Culloty, Sarah; Whooley, Jason; Stanton, Catherine; Ross, R. Paul

2018-01-01

The body of work relating to the gut microbiota of fish is dwarfed by that on humans and mammals. However, it is a field that has had historical interest and has grown significantly along with the expansion of the aquaculture industry and developments in microbiome research. Research is now moving quickly in this field. Much recent focus has been on nutritional manipulation and modification of the gut microbiota to meet the needs of fish farming, while trying to maintain host health and welfare. However, the diversity amongst fish means that baseline data from wild fish and a clear understanding of the role that specific gut microbiota play is still lacking. We review here the factors shaping marine fish gut microbiota and highlight gaps in the research. PMID:29780377

Copepod guts as biogeochemical hotspots in the sea

DEFF Research Database (Denmark)

Tang, Kam W.; Glud, Ronnie N.; Glud, Anni

2011-01-01

The environmental conditions inside the gut of Calanus hyperboreus and C. glacialis were measured with microelectrodes. An acidic potential hydrogen (pH) gradient was present in the gut of C. hyperboreus, and the lowest pH recorded was 5.40. The gut pH of a starved copepod decreased by 0.53 after...... the copepod resumed feeding for a few hours, indicating the secretion of acidic digestive fluid. A copepod feeding on Thalassiosira weissflogii (diatom) had slightly lower pH than that feeding on Rhodomonas salina (cryptophyte). Oxygen was undersaturated in the gut of both C. hyperboreus and C. glacialis......, with a steep gradient from the anal opening to the metasome region. The central metasome region was completely anoxic. Food remains in the gut led to a lower oxygen level, and a diatom diet induced a stronger oxygen gradient than a cryptophyte diet. The acidic and suboxic–anoxic environments of the copepod gut...

Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut

Science.gov (United States)

Ganguli, Kriston; Collado, Maria Carmen; Rautava, Jaana; Lu, Lei; Satokari, Reetta; von Ossowski, Ingemar; Reunanen, Justus; de Vos, Willem M.; Palva, Airi; Isolauri, Erika; Salminen, Seppo; Walker, W. Allan; Rautava, Samuli

2015-01-01

Background Bacterial contact in utero modulates fetal and neonatal immune responses. Maternal probiotic supplementation reduces the risk of immune-mediated disease in the infant. We investigated the immunomodulatory properties of live Lactobacillus rhamnosus GG and its SpaC pilus adhesin in human fetal intestinal models. Methods TNF-α mRNA expression was measured by qPCR in a human fetal intestinal organ culture model exposed to live L. rhamnosus GG and proinflammatory stimuli. Binding of recombinant SpaC pilus protein to intestinal epithelial cells was assessed in human fetal intestinal organ culture and the human fetal intestinal epithelial cell line H4 by immunohistochemistry and immunofluorescence, respectively. TLR-related gene expression in fetal ileal organ culture after exposure to recombinant SpaC was assessed by qPCR. Results Live L. rhamnosus GG significantly attenuates pathogen-induced TNF-α mRNA expression in the human fetal gut. Recombinant SpaC protein was found to adhere to the fetal gut and to modulate varying levels of TLR-related gene expression. Conclusion The human fetal gut is responsive to luminal microbes. L. rhamnosus GG significantly attenuates fetal intestinal inflammatory responses to pathogenic bacteria. The L. rhamnosus GG pilus adhesin SpaC binds to immature human intestinal epithelial cells and directly modulates intestinal epithelial cell innate immune gene expression. PMID:25580735

The gut microbiota and its relationship to diet and obesity

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Clarke, Siobhan F.; Murphy, Eileen F.; Nilaweera, Kanishka; Ross, Paul R.; Shanahan, Fergus; O’Toole, Paul W.; Cotter, Paul D.

2012-01-01

Obesity develops from a prolonged imbalance of energy intake and energy expenditure. However, the relatively recent discovery that the composition and function of the gut microbiota impacts on obesity has lead to an explosion of interest in what is now a distinct research field. Here, research relating to the links between the gut microbiota, diet and obesity will be reviewed under five major headings: (1) the gut microbiota of lean and obese animals, (2) the composition of the gut microbiota of lean and obese humans, (3) the impact of diet on the gut microbiota, (4) manipulating the gut microbiota and (5) the mechanisms by which the gut microbiota can impact on weight gain. PMID:22572830

Use of Gifu Anaerobic Medium for culturing 32 dominant species of human gut microbes and its evaluation based on short-chain fatty acids fermentation profiles.

Science.gov (United States)

Gotoh, Aina; Nara, Misaki; Sugiyama, Yuta; Sakanaka, Mikiyasu; Yachi, Hiroyuki; Kitakata, Aya; Nakagawa, Akira; Minami, Hiromichi; Okuda, Shujiro; Katoh, Toshihiko; Katayama, Takane; Kurihara, Shin

2017-10-01

Recently, a "human gut microbial gene catalogue," which ranks the dominance of microbe genus/species in human fecal samples, was published. Most of the bacteria ranked in the catalog are currently publicly available; however, the growth media recommended by the distributors vary among species, hampering physiological comparisons among the bacteria. To address this problem, we evaluated Gifu anaerobic medium (GAM) as a standard medium. Forty-four publicly available species of the top 56 species listed in the "human gut microbial gene catalogue" were cultured in GAM, and out of these, 32 (72%) were successfully cultured. Short-chain fatty acids from the bacterial culture supernatants were then quantified, and bacterial metabolic pathways were predicted based on in silico genomic sequence analysis. Our system provides a useful platform for assessing growth properties and analyzing metabolites of dominant human gut bacteria grown in GAM and supplemented with compounds of interest.

Mnemiopsis leidyi Gut Harbors Seasonally Variant and Commensal Microbial Assemblages

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Mariita, R. M.; Hossain, M. J.; Liles, M. R.; Moss, A.

2016-02-01

Studies have shown that with widespread use of antibiotics in human and domestic animal populations, antibiotic resistance becomes increasingly common in the environment. Estuaries provide ideal conditions for acquisition and dissemination of drug resistance genes because they serve as sinks for pollution. This study aimed to identify M. leidyi microbial diversity and richness and their potential to act as vectors for antibiotic resistance determinants (ARDs). M. leidyi, although native to study area are highly invasive. Metagenomic analyses indicate that there are temporal variations of bacterioplankton assemblages in M. leidyi gut. Overall, Proteobacteria and Actinobacteria are the most abundant phyla. Despite the temporal dynamics in the microbial assemblages in M. leidyi gut, they seem to retain Propionibacterium acnes (gut microbiota in some insects) and select proteobacteria across all seasons. The results contradict previous studies that suggest that M. leidyi does not have constant a microbiota, but only seasonally variant microbial assemblages. Here we reveal the presence of M. leidyi gut ARDs in winter and summer, probably because of the ctenophores' positive geotaxis during rough surface conditions. Genes responsible for resistance to fluoroquinolones, multidrug resistance efflux pumps, mercuric reductase, copper homeostasis and blaR1 genes were observed. This is the first study to demonstrate that M. leidyi harbors constant microbiota and provides a baseline for understanding M. leidyi gut microbial and ARDs ecology. It also suggests that M. leidyi bacterial taxonomic and functional dynamics is influenced by season. Funding: Alabama EPSCoR GRSP fellowship, AU-CMB fellowship, NSF EPS-1158862, USDA-Hatch 370225-310100 (AGM, ML).

Effects of Gut Microbes on Nutrient Absorption and Energy Regulation

OpenAIRE

Krajmalnik-Brown, Rosa; Ilhan, Zehra-Esra; Kang, Dae-Wook; DiBaise, John K.

2012-01-01

Malnutrition may manifest as either obesity or undernutrition. Accumulating evidence suggests that the gut microbiota plays an important role in the harvest, storage, and expenditure of energy obtained from the diet. The composition of the gut microbiota has been shown to differ between lean and obese humans and mice; however, the specific roles that individual gut microbes play in energy harvest remain uncertain. The gut microbiota may also influence the development of conditions characteriz...

Deoxynivalenol, gut microbiota and immunotoxicity: A potential approach?

Science.gov (United States)

Liao, Yuxiao; Peng, Zhao; Chen, Liangkai; Nüssler, Andreas K; Liu, Liegang; Yang, Wei

2018-02-01

Deoxynivalenol (DON, vomitoxin) is the most frequent mycotoxin in grains and grain products. DON contamination in fodder and food is a serious threat for health, since it impairs the immune and gastrointestinal systems of both human and animals. Gut microbiota seems to play a more and more important part in human and animals' health according to related researches. Previous studies implied some associations among gut microbiota, DON and immune system. For example, DON affects immune system as well as the composition and abundance of gut microbiota, and the latter influences immune system as well. In the present short review, we not only provide the available information about the toxic consequences of DON-induced immunotoxicity on different animals and cell lines and discuss its main possible molecule mechanisms, but also summarize research results concerning the role of gut microbiota in DON-induced immunotoxicity and gender differences, with the aim to find some potential therapeutic strategies to tackle DON-induced immunotoxicity. Copyright © 2018 Elsevier Ltd. All rights reserved.

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"

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...

Type I and Type III Interferons Display Different Dependency on Mitogen-Activated Protein Kinases to Mount an Antiviral State in the Human Gut.

Science.gov (United States)

Pervolaraki, Kalliopi; Stanifer, Megan L; Münchau, Stephanie; Renn, Lynnsey A; Albrecht, Dorothee; Kurzhals, Stefan; Senís, Elena; Grimm, Dirk; Schröder-Braunstein, Jutta; Rabin, Ronald L; Boulant, Steeve

2017-01-01

Intestinal epithelial cells (IECs) are constantly exposed to commensal flora and pathogen challenges. How IECs regulate their innate immune response to maintain gut homeostasis remains unclear. Interferons (IFNs) are cytokines produced during infections. While type I IFN receptors are ubiquitously expressed, type III IFN receptors are expressed only on epithelial cells. This epithelium specificity strongly suggests exclusive functions at epithelial surfaces, but the relative roles of type I and III IFNs in the establishment of an antiviral innate immune response in human IECs are not clearly defined. Here, we used mini-gut organoids to define the functions of types I and III IFNs to protect the human gut against viral infection. We show that primary non-transformed human IECs, upon viral challenge, upregulate the expression of both type I and type III IFNs at the transcriptional level but only secrete type III IFN in the supernatant. However, human IECs respond to both type I and type III IFNs by producing IFN-stimulated genes that in turn induce an antiviral state. Using genetic ablation of either type I or type III IFN receptors, we show that either IFN can independently restrict virus infection in human IECs. Importantly, we report, for the first time, differences in the mechanisms by which each IFN establishes the antiviral state. Contrary to type I IFN, the antiviral activity induced by type III IFN is strongly dependent on the mitogen-activated protein kinases signaling pathway, suggesting a pathway used by type III IFNs that non-redundantly contributes to the antiviral state. In conclusion, we demonstrate that human intestinal epithelial cells specifically regulate their innate immune response favoring type III IFN-mediated signaling, which allows for efficient protection against pathogens without producing excessive inflammation. Our results strongly suggest that type III IFN constitutes the frontline of antiviral response in the human gut. We propose that

Cross-talk of human gut with bifidobacteria

Czech Academy of Sciences Publication Activity Database

Trebichavský, Ilja; Rada, V.; Šplíchalová, Alla; Šplíchal, Igor

2009-01-01

Roč. 67, č. 2 (2009), s. 77-82 ISSN 0029-6643 R&D Projects: GA ČR GA523/07/0572 Institutional research plan: CEZ:AV0Z50200510 Keywords : bifidobacteria * gut * innate immunity Subject RIV: EC - Immunology Impact factor: 3.443, year: 2009

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.

Clinical Correlates of Diarrhea and Gut Parasites among Human Immunodeficiency Virus Seropositive Patients

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Elvis Bisong

2017-09-01

Full Text Available Cluster differentiation 4 (CD4 count estimation, which is not readily available in most resource poor settings in Nigeria, is an important indexdetermining commencement of antiretroviral therapy (ART. It is imperative for physicians who come in contact with these patients in such settings to recognize other parameters to evaluate these patients. The clinical correlates of diarrhea and gut parasites among human immunodeficiency virus (HIV-seropositive patients attending our special treatment clinic were studied. Three hundred and forty consenting HIV-positive adult subjects were enrolled. Their stool and blood specimens were collected for a period of three months. Stool samples were analyzed for the presence of diarrhea and gut parasites. The patients were clinically evaluated by physical examination for the presence of pallor, dehydration, oral thrush, wasting lymphadenopathy, dermatitis, skin hyperpigmentation, and finger clubbing. Participants with diarrhea represented 14.1% of the population, while 21.5% harbored one or more parasites. In the subjects with diarrhea, 14.6% harbored gut parasites. The presence of diarrhea was associated with a low CD4 count. Clinically, oral thrush, wasting, and rashes were more reliable predictors of low CD4 count levels; whereas, the presence of pallor, dehydration, wasting, and rashes correlated with the presence of diarrhea. HIV patients presenting with pallor, dehydration, wasting, and rashes should be evaluated for the presence of diarrhea. The clinical variables associated with low CD4 count in this study may guide commencing antiretroviral therapy in resource poor settings.

Characterization of gut bacterial flora of Apis mellifera from north-west Pakistan

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Syed Ishtiaq Anjum

2018-02-01

Full Text Available Gut microbiota has been recognized to play a beneficial role in honey bees (Apis mellifera. Present study was designed to characterize the gut bacterial flora of honey bees in north-west Pakistan. Total 150 aerobic and facultative anaerobic bacteria from guts of 45 worker bees were characterized using biochemical assays and 16S rDNA sequencing followed by bioinformatics analysis. The gut isolates were classified into three bacterial phyla of Firmicutes (60%, Proteobacteria (26% and Actinobacteria (14%. Most of the isolates belonged to genera and families of Staphylococcus, Bacillus, Enterococcus, Ochrobactrum, Sphingomonas, Ralstonia, Enterobacteriaceae, Corynebacterium and Micrococcineae. Many of these bacteria were tolerant to acidic environments and fermented sugars, hence considered beneficial gut inhabitants and involved the maintenance of a healthy microbiota. However, several opportunistic commensals that proliferate in the hive environment including members Staphylococcus haemolyticus group and Sphingomonas paucimobilis were also identified. This is the first report on bee gut microbiota from north-west Pakistan geographically situated at the crossroads of Indian subcontinent and central Asia.

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 ...

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...

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

Human, donkey and cow milk differently affects energy efficiency and inflammatory state by modulating mitochondrial function and gut microbiota.

Science.gov (United States)

Trinchese, Giovanna; Cavaliere, Gina; Canani, Roberto Berni; Matamoros, Sebastien; Bergamo, Paolo; De Filippo, Chiara; Aceto, Serena; Gaita, Marcello; Cerino, Pellegrino; Negri, Rossella; Greco, Luigi; Cani, Patrice D; Mollica, Maria Pina

2015-11-01

Different nutritional components are able, by modulating mitochondrial function and gut microbiota composition, to influence body composition, metabolic homeostasis and inflammatory state. In this study, we aimed to evaluate the effects produced by the supplementation of different milks on energy balance, inflammatory state, oxidative stress and antioxidant/detoxifying enzyme activities and to investigate the role of the mitochondrial efficiency and the gut microbiota in the regulation of metabolic functions in an animal model. We compared the intake of human milk, gold standard for infant nutrition, with equicaloric supplementation of donkey milk, the best substitute for newborns due to its nutritional properties, and cow milk, the primary marketed product. The results showed a hypolipidemic effect produced by donkey and human milk intake in parallel with enhanced mitochondrial activity/proton leakage. Reduced mitochondrial energy efficiency and proinflammatory signals (tumor necrosis factor α, interleukin-1 and lipopolysaccharide levels) were associated with a significant increase of antioxidants (total thiols) and detoxifying enzyme activities (glutathione-S-transferase, NADH quinone oxidoreductase) in donkey- and human milk-treated animals. The beneficial effects were attributable, at least in part, to the activation of the nuclear factor erythroid-2-related factor-2 pathway. Moreover, the metabolic benefits induced by human and donkey milk may be related to the modulation of gut microbiota. In fact, milk treatments uniquely affected the proportions of bacterial phyla and genera, and we hypothesized that the increased concentration of fecal butyrate in human and donkey milk-treated rats was related to the improved lipid and glucose metabolism and detoxifying activities. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

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...

ERIC-PCR fingerprinting-based community DNA hybridization to pinpoint genome-specific fragments as molecular markers to identify and track populations common to healthy human guts.

Science.gov (United States)

Wei, Guifang; Pan, Li; Du, Huimin; Chen, Junyi; Zhao, Liping

2004-10-01

Bacterial populations common to healthy human guts may play important roles in human health. A new strategy for discovering genomic sequences as markers for these bacteria was developed using Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR fingerprinting. Structural features within microbial communities are compared with ERIC-PCR followed by DNA hybridization to identify genomic fragments shared by samples from healthy human individuals. ERIC-PCR profiles of fecal samples from 12 diseased or healthy human and piglet subjects demonstrated stable, unique banding patterns for each individual tested. Sequence homology of DNA fragments in bands of identical size was examined between samples by hybridization under high stringency conditions with DIG-labeled ERIC-PCR products derived from the fecal sample of one healthy child. Comparative analysis of the hybridization profiles with the original agarose fingerprints identified three predominant bands as signatures for populations associated with healthy human guts with sizes of 500, 800 and 1000 bp. Clone library profiling of the three bands produced 17 genome fragments, three of which showed high similarity only with regions of the Bacteroides thetaiotaomicron genome, while the remainder were orphan sequences. Association of these sequences with healthy guts was validated by sequence-selective PCR experiments, which showed that a single fragment was present in all 32 healthy humans and 13 healthy piglets tested. Two fragments were present in the healthy human group and in 18 children with non-infectious diarrhea but not in eight children with infectious diarrhea. Genome fragments identified with this novel strategy may be used as genome-specific markers for dynamic monitoring and sequence-guided isolation of functionally important bacterial populations in complex communities such as human gut microflora.

Gut symbiotic microbes imprint intestinal immune cells with the innate receptor SLAMF4 which contributes to gut immune protection against enteric pathogens.

Science.gov (United States)

Cabinian, Allison; Sinsimer, Daniel; Tang, May; Jang, Youngsoon; Choi, Bongkum; Laouar, Yasmina; Laouar, Amale

2018-05-01

Interactions between host immune cells and gut microbiota are crucial for the integrity and function of the intestine. How these interactions regulate immune cell responses in the intestine remains a major gap in the field. We have identified the signalling lymphocyte activation molecule family member 4 (SLAMF4) as an immunomodulator of the intestinal immunity. The aim is to determine how SLAMF4 is acquired in the gut and what its contribution to intestinal immunity is. Expression of SLAMF4 was assessed in mice and humans. The mechanism of induction was studied using GFP tg bone marrow chimaera mice, lymphotoxin α and TNLG8A-deficient mice, as well as gnotobiotic mice. Role in immune protection was revealed using oral infection with Listeria monocytogenes and Cytobacter rodentium . SLAMF4 is a selective marker of intestinal immune cells of mice and humans. SLAMF4 induction occurs directly in the intestinal mucosa without the involvement of the gut-associated lymphoid tissue. Gut bacterial products, particularly those of gut anaerobes, and gut-resident antigen-presenting cell (APC) TNLG8A are key contributors of SLAMF4 induction in the intestine. Importantly, lack of SLAMF4 expression leads the increased susceptibility of mice to infection by oral pathogens culminating in their premature death. SLAMF4 is a marker of intestinal immune cells which contributes to the protection against enteric pathogens and whose expression is dependent on the presence of the gut microbiota. This discovery provides a possible mechanism for answering the long-standing question of how the intertwining of the host and gut microbial biology regulates immune cell responses in the gut. 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/.

Immunogenic properties of the human gut-associated archaeon Methanomassiliicoccus luminyensis and its susceptibility to antimicrobial peptides.

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Corinna Bang

Full Text Available The methanogenic archaeon Methanomassiliicoccus luminyensis strain B10T was isolated from human feces just a few years ago. Due to its remarkable metabolic properties, particularly the degradation of trimethylamines, this strain was supposed to be used as "Archaebiotic" during metabolic disorders of the human intestine. However, there is still no data published regarding adaptations to the natural habitat of M. luminyensis as it has been shown for the other two reported mucosa-associated methanoarchaea. This study aimed at unraveling susceptibility of M. luminyensis to antimicrobial peptides as well as its immunogenicity. By using the established microtiter plate assay adapted to the anaerobic growth requirements of methanogenic archaea, we demonstrated that M. luminyensis is highly sensitive against LL32, a derivative of human cathelicidin (MIC = 2 μM. However, the strain was highly resistant against the porcine lysin NK-2 (MIC = 10 μM and the synthetic antilipopolysaccharide peptide (Lpep (MIC>10 μM and overall differed from the two other methanoarchaea, Methanobrevibacter smithii and Methanosphaera stadtmanae in respect to AMP sensitivity. Moreover, only weak immunogenic potential of M. luminyensis was demonstrated using peripheral blood mononuclear cells (PBMCs and monocyte-derived dendritic cells (moDCs by determining release of pro-inflammatory cytokines. Overall, our findings clearly demonstrate that the archaeal gut inhabitant M. luminyensis is susceptible to the release of human-derived antimicrobial peptides and exhibits low immunogenicity towards human immune cells in vitro-revealing characteristics of a typical commensal gut microbe.

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....

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...

Transfer factors across the human gut for plutonium and americium in shellfish from near Sellafield

International Nuclear Information System (INIS)

Hunt, G.J.; Leonard, D.R.P.; Lovett, M.B.

1988-01-01

Data on gut transfer factors for environmental forms of radionuclides are essential for estimates of public radiation exposures following ingestion, and thus in decisions on controlling waste disposals. Dose estimates for transuranic nuclides are particularly sensitive to uncertainties stemming from gut transfer data being related to non-environmental forms and/or derived from animal experiments. The main parameter in question is f 1 , the fraction of intake reaching human body fluids following ingestion, as applied in the model of the gastro-intestinal tract used by the ICRP. The ICRP have recently reviewed the metabolism of plutonium and related elements (ICRP, 1986). Values of f 1 were derived from animal data; limited verification was provided by the only human data then available which was based on the low levels of fallout in foodstuffs. The ICRP proposed a cautious value of f 1 of 10 -3 for unknown or mixed compounds of Pu and for other actinides. However, it was recognised that this cautious value may not be appropriate in all situations where a best estimate of absorption is required; in such cases, if a different value more suitable to the specific situation can be justified, it should be employed

Patterns of Early-Life Gut Microbial Colonization during Human Immune Development: An Ecological Perspective

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Isabelle Laforest-Lapointe

2017-07-01

Full Text Available Alterations in gut microbial colonization during early life have been reported in infants that later developed asthma, allergies, type 1 diabetes, as well as in inflammatory bowel disease patients, previous to disease flares. Mechanistic studies in animal models have established that microbial alterations influence disease pathogenesis via changes in immune system maturation. Strong evidence points to the presence of a window of opportunity in early life, during which changes in gut microbial colonization can result in immune dysregulation that predisposes susceptible hosts to disease. Although the ecological patterns of microbial succession in the first year of life have been partly defined in specific human cohorts, the taxonomic and functional features, and diversity thresholds that characterize these microbial alterations are, for the most part, unknown. In this review, we summarize the most important links between the temporal mosaics of gut microbial colonization and the age-dependent immune functions that rely on them. We also highlight the importance of applying ecology theory to design studies that explore the interactions between this complex ecosystem and the host immune system. Focusing research efforts on understanding the importance of temporally structured patterns of diversity, keystone groups, and inter-kingdom microbial interactions for ecosystem functions has great potential to enable the development of biologically sound interventions aimed at maintaining and/or improving immune system development and preventing disease.

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.

Effect of antibiotics on gut microbiota, glucose metabolism and bodyweight regulation

DEFF Research Database (Denmark)

Mikkelsen, Kristian Hallundbaek; Allin, Kristine Højgaard; Knop, Filip Krag

2016-01-01

Gut bacteria are involved in a number of host metabolic processes and have been implicated in the development of obesity and type 2 diabetes in humans. Use of antibiotics changes the composition of the gut microbiota and there is accumulating evidence from observational studies for an association...... between exposure to antibiotics and development of obesity and type 2 diabetes. Here we review human studies examining effects of antibiotics on bodyweight regulation and glucose metabolism and discuss whether the observed findings may relate to alterations in the composition and function of the gut...

Gut microbiota may have influence on glucose and lipid metabolism

DEFF Research Database (Denmark)

Mikkelsen, Kristian Hallundbæk; Nielsen, Morten Frost; Tvede, Michael

2013-01-01

and that prebiotics, antibiotics or faecal transplantation can alter glucose and lipid metabolism. This paper summarizes the latest research regarding the association between gut microbiota, diabetes and obesity and some of the mechanisms by which gut bacteria may influence host metabolism.......New gene sequencing-based techniques and the large worldwide sequencing capacity have introduced a new era within the field of gut microbiota. Animal and human studies have shown that obesity and type 2 diabetes are associated with changes in the composition of the gut microbiota...

Gut microbiota may have influence on glucose and lipid metabolism

DEFF Research Database (Denmark)

Mikkelsen, Kristian Hallundbæk; Nielsen, Morten Frost; Tvede, Michael

2013-01-01

New gene sequencing-based techniques and the large worldwide sequencing capacity have introduced a new era within the field of gut microbiota. Animal and human studies have shown that obesity and type 2 diabetes are associated with changes in the composition of the gut microbiota...... and that prebiotics, antibiotics or faecal transplantation can alter glucose and lipid metabolism. This paper summarizes the latest research regarding the association between gut microbiota, diabetes and obesity and some of the mechanisms by which gut bacteria may influence host metabolism....

Gut Microbiota: From Fundamental Research to Translational Medicine

Directory of Open Access Journals (Sweden)

Yujing Bi

2015-12-01

Full Text Available The human microbiota is a hot topic at present because increasing evidences demonstrate that it should be considered an organ based on its importance to human health. Dysbiosis of the gut microbiota is significantly related to many human disorders. In turn, correcting such imbalances and taking advantage of gut microbes are possible methods for alleviating or even curing host diseases. A recent study published in Cell indicated that inhibition of gut microbial production of trimethylamine(TMA specifically prevents atherosclerosis in vivo. Another study found that a diet supplemented with TMA N-oxide (TMAO increased the level of atherosclerosis in mice, which suggested TMAO might be a causative factor in cardiovascular disease (CVD. However, direct inhibition of flavin-containing monooxygenase (FMO3, a hepatic enzyme that catalyzes the conversion of TMA to TMAO, results in TMA accumulation and several unpleasant side effects. The small-molecule 3, 3-dimethyl-1-butanol (DMB, identified by Wang et al., reduces TMAO through non-lethal inhibition of microbial TMA formation in mice, even when fed a western diet, including high choline. DMB is a non-toxic compound found naturally in foods such as olive oil and red wine. Therefore, the risk of CVD could be reduced by some dietary habits (such as a Mediterranean diet, which might stem from changes in gut microbiota. Although the impact of DMB on microbial TMA has only been observed in mouse models, it provides a guideline for the treatment of CVD in humans by regulating gut microbes. There are many similar studies that target gut microbes to treat host disorders. For example, Sarkis’ group verified that a human commensal bacterium could improve autism spectrum disorder (ASD-related gastrointestinal deficits and behavioral abnormalities in mice, which indicated that microbiome-mediated therapies might be a safe and effective treatment for ASD. In addition, fecal microbiota transplantation, which has

Antioxidants keep the potentially probiotic but highly oxygen-sensitive human gut bacterium Faecalibacterium prausnitzii alive at ambient air

NARCIS (Netherlands)

Khan, M. Tanweer; van Dijl, Jan Maarten; Harmsen, Hermie J M

2014-01-01

The beneficial human gut microbe Faecalibacterium prausnitzii is a 'probiotic of the future' since it produces high amounts of butyrate and anti-inflammatory compounds. However, this bacterium is highly oxygen-senstive, making it notoriously difficult to cultivate and preserve. This has so far

Environmental Pollutant Benzo[a]Pyrene Impacts the Volatile Metabolome and Transcriptome of the Human Gut Microbiota.

Science.gov (United States)

Defois, Clémence; Ratel, Jérémy; Denis, Sylvain; Batut, Bérénice; Beugnot, Réjane; Peyretaillade, Eric; Engel, Erwan; Peyret, Pierre

2017-01-01

Benzo[ a ]pyrene (B[ a ]P) is a ubiquitous, persistent, and carcinogenic pollutant that belongs to the large family of polycyclic aromatic hydrocarbons. Population exposure primarily occurs via contaminated food products, which introduces the pollutant to the digestive tract. Although the metabolism of B[ a ]P by host cells is well known, its impacts on the human gut microbiota, which plays a key role in health and disease, remain unexplored. We performed an in vitro assay using 16S barcoding, metatranscriptomics and volatile metabolomics to study the impact of B[ a ]P on two distinct human fecal microbiota. B[ a ]P exposure did not induce a significant change in the microbial structure; however, it altered the microbial volatolome in a dose-dependent manner. The transcript levels related to several metabolic pathways, such as vitamin and cofactor metabolism, cell wall compound metabolism, DNA repair and replication systems, and aromatic compound metabolism, were upregulated, whereas the transcript levels related to the glycolysis-gluconeogenesis pathway and bacterial chemotaxis toward simple carbohydrates were downregulated. These primary findings show that food pollutants, such as B[ a ]P, alter human gut microbiota activity. The observed shift in the volatolome demonstrates that B[ a ]P induces a specific deviation in the microbial metabolism.

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.

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.

Synbiotic Lactobacillus acidophilus NCFM and cellobiose does not affect human gut bacterial diversity but increases abundance of lactobacilli, bifidobacteria and branched-chain fatty acids: a randomized, double-blinded cross-over trial

DEFF Research Database (Denmark)

van Zanten, Gabriella Christina; Krych, Lukasz; Roytio, Henna

2014-01-01

Probiotics, prebiotics, and combinations thereof, that is synbiotics, have been reported to modulate gut microbiota of humans. In this study, effects of a novel synbiotic on the composition and metabolic activity of human gut microbiota were investigated. Healthy volunteers (n=18) were enrolled i...

Gut microbiota modify risk for dietary glycemia-induced age-related macular degeneration.

Science.gov (United States)

Rowan, Sheldon; Taylor, Allen

2018-03-21

Age-related macular degeneration (AMD) is a leading cause of blindness world-wide. Although the etiology of AMD is multifactorial, diet and nutrition have strong epidemiologic associations with disease onset and progression. Recent studies indicate a role for gut microbiota in development of AMD in mouse models and in some forms of human AMD. We previously found that consuming lower glycemia diets is associated with protection against AMD in humans and switching from higher to lower glycemia diets arrests AMD phenotypes in mice. Gut microbiota populations and circulating microbial cometabolites were altered in response to dietary carbohydrates, indicating a gut-retina axis. Here we explore additional gut microbiota-AMD interactions that point toward pathogenic roles for some gut microbiota families, including Ruminococcaceae and Lachnospiraceae, and individual members of Turicibacteraceae, Clostridiaceae, and Mogibacteriaceae. We also speculate on potential mechanisms by which gut microbiota influence AMD, with the objective of devising new AMD diagnoses and treatments.

Immune Response of Chicken Gut to Natural Colonization by Gut Microflora and to Salmonella enterica Serovar Enteritidis Infection ▿

OpenAIRE

Crhanova, Magdalena; Hradecka, Helena; Faldynova, Marcela; Matulova, Marta; Havlickova, Hana; Sisak, Frantisek; Rychlik, Ivan

2011-01-01

In commercial poultry production, there is a lack of natural flora providers since chickens are hatched in the clean environment of a hatchery. Events occurring soon after hatching are therefore of particular importance, and that is why we were interested in the development of the gut microbial community, the immune response to natural microbial colonization, and the response to Salmonella enterica serovar Enteritidis infection as a function of chicken age. The complexity of chicken gut micro...

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.

Transfer across the human gut of environmental technetium in lobsters (Homarus gammarus L.) from the Irish Sea

Energy Technology Data Exchange (ETDEWEB)

Hunt, G.J. [The Centre for Environment, Fisheries and Aquaculture Science, Lowestoft Laboratory, Pakefield Road, Lowestoft, Suffolk NR33 0HT (United Kingdom)]. E-mail: g.j.hunt@cefas.co.uk; Young, A.K.; Bonfield, R.A. [The Centre for Environment, Fisheries and Aquaculture Science, Lowestoft Laboratory, Pakefield Road, Lowestoft, Suffolk NR33 0HT (United Kingdom)

2001-03-01

Few data are available on the uptake by the human gut of the element technetium. Of current radiological interest in connection with discharges of technetium-99 in liquid discharges from BNFL, Sellafield, is uptake from European lobsters (Homarus gammarus), whose edible parts are known to concentrate technetium. In this study, a group of eight adult volunteers (six males and two females) ate samples of edible flesh from lobsters caught off the west Cumbrian coast and provided 24 h samples of urine and faeces for analysis. Detection of uptake from the gut by difference between intake and faecal measurements proved insensitive, suggesting a low value of the gut transfer factor (f{sub 1} value) of up to 0.1 with a maximum (two standard deviations) level of about 0.3. In urine, technetium was detectable at a relatively low level compared with the intakes, consistent with a low absorption across the gut. Values for f{sub 1} were derived with the aid of literature data for excretion following intravenous administration of technetium-95m as pertechnetate, and gave averaged data for f{sub 1} in the range 0.046 to 0.23. These results are in broad conformity with those derived from the faecal measurements, and suggest a lower value than the 0.5 used by ICRP. (author)

Transfer of environmental plutonium and americium across the human gut

International Nuclear Information System (INIS)

Hunt, G.J.; Leonard, D.R.P.; Lovett, M.B.

1989-01-01

Following the ingestion of winkles obtained from a coastal area near Sellafield nuclear reprocessing plant, a group of volunteers provided urine for the next 7 days to be analysed for plutonium and americium. From this, estimates of the intake and gut transfer factors for these isotopes were determined. Preliminary estimates of gut transfer factors from a previous study by the same authors were then re-interpreted and combined with the results from the present study. (UK)

Amidated joining peptide in the human pituitary, gut, adrenal gland and bronchial carcinoids. Immunocytochemical and immunochemical evidence

DEFF Research Database (Denmark)

Bjartell, A; Fenger, M; Ekman, R

1990-01-01

The distribution of the proopiomelanocortin-derivated amidated joining peptide (JP-N) was examined in the human pituitary gland, adrenal gland, gut and in three bronchial carcinoids. Double immunostaining showed coexistence of immunoreactive JP-N and other proopiomelanocortin derivatives, e......-N, respectively, but under reduced conditions most of the immunoreactive material appeared as of low molecular weight in both extracts. In conclusion, immunoreactive JP-N is a major product from the processing of proopiomelanocortin in human extrapituitary tissues. The molecular forms of immunoreactive JP......-N correspond to previous findings in the human pituitary gland....

Obesity-Related Diseases Dietary Modulation of the Gut Microbiota

DEFF Research Database (Denmark)

Brahe, Lena Kirchner

strategies to reduce obesity-related morbidity and mortality are essential. It has been hypothesized that the microbes in the human gut are involved in the development of obesity-related diseases and that intake of nutrients affecting the gut microbial community in specific ways, can be a new strategy...

Probiotic Species in the Modulation of Gut Microbiota: An Overview

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Md. Abul Kalam Azad

2018-01-01

Full Text Available Probiotics are microbial strains that are beneficial to health, and their potential has recently led to a significant increase in research interest in their use to modulate the gut microbiota. The animal gut is a complex ecosystem of host cells, microbiota, and available nutrients, and the microbiota prevents several degenerative diseases in humans and animals via immunomodulation. The gut microbiota and its influence on human nutrition, metabolism, physiology, and immunity are addressed, and several probiotic species and strains are discussed to improve the understanding of modulation of gut microbiota. This paper provides a broad review of several Lactobacillus spp., Bifidobacterium spp., and other coliform bacteria as the most promising probiotic species and their role in the prevention of degenerative diseases, such as obesity, diabetes, cancer, cardiovascular diseases, malignancy, liver disease, and inflammatory bowel disease. This review also discusses a recent study of Saccharomyces spp. in which inflammation was prevented by promotion of proinflammatory immune function via the production of short-chain fatty acids. A summary of gut microbiota alteration with future perspectives is also provided.

Gut microbiota in experimental murine model of Graves' orbitopathy established in different environments may modulate clinical presentation of disease.

Science.gov (United States)

Masetti, Giulia; Moshkelgosha, Sajad; Köhling, Hedda-Luise; Covelli, Danila; Banga, Jasvinder Paul; Berchner-Pfannschmidt, Utta; Horstmann, Mareike; Diaz-Cano, Salvador; Goertz, Gina-Eva; Plummer, Sue; Eckstein, Anja; Ludgate, Marian; Biscarini, Filippo; Marchesi, Julian Roberto

2018-05-25

Variation in induced models of autoimmunity has been attributed to the housing environment and its effect on the gut microbiota. In Graves' disease (GD), autoantibodies to the thyrotropin receptor (TSHR) cause autoimmune hyperthyroidism. Many GD patients develop Graves' orbitopathy or ophthalmopathy (GO) characterized by orbital tissue remodeling including adipogenesis. Murine models of GD/GO would help delineate pathogenetic mechanisms, and although several have been reported, most lack reproducibility. A model comprising immunization of female BALBc mice with a TSHR expression plasmid using in vivo electroporation was reproduced in two independent laboratories. Similar orbital disease was induced in both centers, but differences were apparent (e.g., hyperthyroidism in Center 1 but not Center 2). We hypothesized a role for the gut microbiota influencing the outcome and reproducibility of induced GO. We combined metataxonomics (16S rRNA gene sequencing) and traditional microbial culture of the intestinal contents from the GO murine model, to analyze the gut microbiota in the two centers. We observed significant differences in alpha and beta diversity and in the taxonomic profiles, e.g., operational taxonomic units (OTUs) from the genus Lactobacillus were more abundant in Center 2, and Bacteroides and Bifidobacterium counts were more abundant in Center 1 where we also observed a negative correlation between the OTUs of the genus Intestinimonas and TSHR autoantibodies. Traditional microbiology largely confirmed the metataxonomics data and indicated significantly higher yeast counts in Center 1 TSHR-immunized mice. We also compared the gut microbiota between immunization groups within Center 2, comprising the TSHR- or βgal control-immunized mice and naïve untreated mice. We observed a shift of the TSHR-immunized mice bacterial communities described by the beta diversity weighted Unifrac. Furthermore, we observed a significant positive correlation between the

Emerging Technologies for Gut Microbiome Research

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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

Links between Dietary Protein Sources, the Gut Microbiota, and Obesity

OpenAIRE

Lise Madsen; Lise Madsen; Lise Madsen; Lene S. Myrmel; Even Fjære; Bjørn Liaset; Karsten Kristiansen; Karsten Kristiansen

2017-01-01

The association between the gut microbiota and obesity is well documented in both humans and in animal models. It is also demonstrated that dietary factors can change the gut microbiota composition and obesity development. However, knowledge of how diet, metabolism and gut microbiota mutually interact and modulate energy metabolism and obesity development is still limited. Epidemiological studies indicate an association between intake of certain dietary protein sources and obesity. Animal stu...

Links between dietary protein sources, the gut microbiota, and obesity

OpenAIRE

Madsen, Lise; Myrmel, Lene S.; Fjære, Even; Liaset, Bjørn; Kristiansen, Karsten

2017-01-01

The association between the gut microbiota and obesity is well documented in both humans and in animal models. It is also demonstrated that dietary factors can change the gut microbiota composition and obesity development. However, knowledge of how diet, metabolism and gut microbiota mutually interact and modulate energy metabolism and obesity development is still limited. Epidemiological studies indicate an association between intake of certain dietary protein sources and obesity. Animal stu...

Assessing the Influence of Vegan, Vegetarian and Omnivore Oriented Westernized Dietary Styles on Human Gut Microbiota: A Cross Sectional Study.

Science.gov (United States)

Losasso, Carmen; Eckert, Ester M; Mastrorilli, Eleonora; Villiger, Jorg; Mancin, Marzia; Patuzzi, Ilaria; Di Cesare, Andrea; Cibin, Veronica; Barrucci, Federica; Pernthaler, Jakob; Corno, Gianluca; Ricci, Antonia

2018-01-01

Diet and lifestyle have a strong influence on gut microbiota, which in turn has important implications on a variety of health-related aspects. Despite great advances in the field, it remains unclear to which extent the composition of the gut microbiota is modulated by the intake of animal derived products, compared to a vegetable based diet. Here the specific impact of vegan, vegetarian, and omnivore feeding type on the composition of gut microbiota of 101 adults was investigated among groups homogeneous for variables known to have a role in modulating gut microbial composition such as age, anthropometric variables, ethnicity, and geographic area. The results displayed a picture where the three different dietetic profiles could be well distinguished on the basis of participant's dietetic regimen. Regarding the gut microbiota; vegetarians had a significantly greater richness compared to omnivorous. Moreover, counts of Bacteroidetes related operational taxonomic units (OTUs) were greater in vegans and vegetarians compared to omnivores. Interestingly considering the whole bacterial community composition the three cohorts were unexpectedly similar, which is probably due to their common intake in terms of nutrients rather than food, e.g., high fat content and reduced protein and carbohydrate intake. This finding suggests that fundamental nutritional choices such as vegan, vegetarian, or omnivore do influence the microbiota but do not allow to infer conclusions on gut microbial composition, and suggested the possibility for a preferential impact of other variables, probably related to the general life style on shaping human gut microbial community in spite of dietary influence. Consequently, research were individuals are categorized on the basis of their claimed feeding types is of limited use for scientific studies, since it appears to be oversimplified.

Gut Microbiota: From Microorganisms to Metabolic Organ Influencing Obesity.

Science.gov (United States)

Stephens, Richard W; Arhire, Lidia; Covasa, Mihai

2018-05-01

This review summarizes the current understanding of the relationship between gut microbiota and the host as it pertains to the regulation of energy balance and obesity. The paper begins with a brief description of the gut microbiota environment, distribution, and its unique symbiotic relationship with the host. The way that enviromental factors influence microbiota composition and subsequent impact on the host are then described. Next, the mechanisms linking gut dysbiosis with obesity are discussed, and finally current challenges and limitations in understanding the role of gut microbiota in control of obesity are presented. Gut microbiota has been implicated in regulation of fat storage, as well as gut dysbiosis, thus contributing to the development of obesity, insulin resistance, hyperglycemia and hyperlipidemia. However, the underlying mechanisms of these processes are far from being clear and will require complex preclinical and clinical interdisciplinary studies of bacteria and host cell-to-cell interactions. There is a need for a better understanding of how changes in gut microbiota composition can impact energy balance and thus control weight gain. This may represent a promising avenue in the race to develop nonsurgical treatments for obesity. © 2018 The Obesity Society.

Crosstalk between Bile Acids and Gut Microbiota and Its Impact on Farnesoid X Receptor Signalling

DEFF Research Database (Denmark)

Wahlström, Annika; Kovatcheva-Datchary, Petia; Ståhlman, Marcus

2017-01-01

Background: The gut microbiota has a substantial impact on health and disease. The human gut microbiota influences the development and progression of metabolic diseases; however, the underlying mechanisms are not fully understood. The nuclear farnesoid X receptor (FXR), which regulates bile acid...... homeostasis and glucose and lipid metabolism, is activated by primary human and murine bile acids, chenodeoxycholic acid and cholic acid, while rodent specific primary bile acids tauromuricholic acids antagonise FXR activation. The gut microbiota deconjugates and subsequently metabolises primary bile acids...... into secondary bile acids in the gut and thereby changes FXR activation and signalling. Key Message: Mouse models have been used to study the crosstalk between bile acids and the gut microbiota, but the substantial differences in bile acid composition between humans and mice need to be considered when...

Simultaneous gut colonisation and infection by ESBL-producing Escherichia coli in hospitalised patients.

Science.gov (United States)

Asir, Johny; Nair, Shashikala; Devi, Sheela; Prashanth, Kenchappa; Saranathan, Rajagopalan; Kanungo, Reba

2015-01-01

Extended spectrum betalactamase (ESBL)-producing organisms are a major cause of hospital-acquired infections. ESBL-producing Escherichia coli (E. coli) have been recovered from the hospital environment. These drug-resistant organisms have also been found to be present in humans as commensals. The present investigation intended to isolate ESBL-producing E. coli from the gut of already infected patients; to date, only a few studies have shown evidence of the gut microflora as a major source of infection. This study aimed to detect the presence of ESBL genes in E.coli that are isolated from the gut of patients who have already been infected with the same organism. A total of 70 non-repetitive faecal samples were collected from in-patients of our hospital. These in-patients were clinically diagnosed and were culture-positive for ESBL-producing E. coli either from blood, urine, or pus. Standard microbiological methods were used to detect ESBL from clinical and gut isolates. Genes coding for major betalactamase enzymes such as bla CTX-M , bla TEM, and bla SHV were investigated by polymerase chain reaction (PCR). ESBL-producing E. coli was isolated from 15 (21 per cent) faecal samples of the 70 samples that were cultured. PCR revealed that out of these 15 isolates, the bla CTX-M gene was found in 13 (86.6 per cent) isolates, the bla TEM was present in 11 (73.3 per cent) isolates, and bla SHV only in eight (53.3 per cent) isolates. All 15 clinical and gut isolates had similar phenotypic characters and eight of the 15 patients had similar pattern of genes (bla TEM, bla CTX-M, and bla SHV) in their clinical and gut isolates. Strains with multiple betalactamase genes that colonise the gut of hospitalised patients are a potential threat and it may be a potential source of infection.

Diet, Environments, and Gut Microbiota. A Preliminary Investigation in Children Living in Rural and Urban Burkina Faso and Italy

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Carlotta De Filippo

2017-10-01

Full Text Available Diet is one of the main factors that affects the composition of gut microbiota. When people move from a rural environment to urban areas, and experience improved socio-economic conditions, they are often exposed to a “globalized” Western type diet. Here, we present preliminary observations on the metagenomic scale of microbial changes in small groups of African children belonging to the same ethnicity and living in different environments, compared to children living on the urban area of Florence (Italy. We analyzed dietary habits and, by pyrosequencing of the 16S rRNA gene, gut microbiota profiles from fecal samples of children living in a rural village of Burkina Faso (n = 11, of two groups of children living in different urban settings (Nanoro town, n = 8; Ouagadougou, the capital city, n = 5 and of a group of Italian children (n = 13. We observed that when foods of animal origin, those rich in fat and simple sugars are introduced into a traditional African diet, composed of cereals, legumes and vegetables, the gut microbiota profiles changes. Microbiota of rural children retain a geographically unique bacterial reservoir (Prevotella, Treponema, and Succinivibrio, assigned to ferment fiber and polysaccharides from vegetables. Independently of geography and ethnicity, in children living in urban areas these bacterial genera were progressively outcompeted by bacteria more suited to the metabolism of animal protein, fat and sugar rich foods, similarly to Italian children, as resulted by PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States, a predictive functional profiling of microbial communities using 16S rRNA marker gene. Consequently, we observed a progressive reduction of SCFAs measured by gas chromatography–mass spectrometry, in urban populations, especially in Italian children, respect to rural ones. Our results even if in a limited number of individuals point out that dietary habit modifications

The human obesity epidemic, the mismatch paradigm, and our modern "captive" environment.

Science.gov (United States)

Power, Michael L

2012-01-01

In the distant past obesity in humans was rare and likely caused by metabolic dysregulation due to genetic or disease-related pathology. External factors precluded the ability of most people to overeat or under exert. Socio-cultural obesity came about due to the rareness of obesity and its difficulty to achieve. What is rare becomes valuable and what is difficult to achieve becomes a badge of prestige. The modern human obesity epidemic would appear to represent a third class of obesity: environmental obesity. Much like the captive environments which humans construct for the captive/companion animals in our care, the modern human environment has greatly decreased the challenges of life that would restrict food intake and enforce exertion. And like us, our captive/companion animal populations are also experiencing obesity epidemics. A further concern is that maternal obesity alters maternal signaling to offspring, in utero through the placenta and after birth through breast milk, in ways that perpetuate an enhanced vulnerability to obesity. Molecules such as leptin, produced by adipose tissue and placenta, have significant developmental effects on brain areas associated with feeding behavior. Leptin and other cytokines and growth factors are found in breast milk. These molecules have positive effects on gut maturation; their effects on metabolism and brain development are unclear. Placenta and brain also are hotspots for epigenetic regulation, and epigenetic changes may play significant roles in the later vulnerability to obesity and to the development of a diverse array of diseases, including heart disease, hypertension, and noninsulin-dependent diabetes. Copyright © 2012 Wiley Periodicals, Inc.

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....

Bacterial Impact on the Gut Metabolome

DEFF Research Database (Denmark)

Sulek, Karolina; Wilcks, Andrea; Licht, Tine Rask

During the last decade, it has become evident that the complex ecosystem of mi-crobes inhabiting the human gut plays an important role for human health. An in-creasing number of publications have shown that the composition and activity of our intestinal microbiota affects a number of different so...

Cardiovascular and Antiobesity Effects of Resveratrol Mediated through the Gut Microbiota.

Science.gov (United States)

Bird, Julia K; Raederstorff, Daniel; Weber, Peter; Steinert, Robert E

2017-11-01

Encouraging scientific research into the health effects of dietary bioactive resveratrol has been confounded by its rapid first-pass metabolism, which leads to low in vivo bioavailability. Preliminary studies have shown that resveratrol can modulate gut microbiota composition, undergo biotransformation to active metabolites via the intestinal microbiota, or affect gut barrier function. In rodents, resveratrol can modify the relative Bacteroidetes:Firmicutes ratio and reverse the gut microbial dysbiosis caused by a high-fat diet. By upregulating the expression of genes involved in maintaining tight junctions between intestinal cells, resveratrol contributes to gut barrier integrity. The composition of the gut microbiome and rapid metabolism of resveratrol determines the production of resveratrol metabolites, which are found at greater concentrations in humans after ingestion than their parent molecule and can have similar biological effects. Resveratrol may affect cardiovascular risk factors such as elevated blood cholesterol or trimethylamine N -oxide concentrations. Modulating the composition of the gut microbiota by resveratrol may affect central energy metabolism and modify concentrations of satiety hormones to produce antiobesity effects. Encouraging research from animal models could be tested in humans. © 2017 American Society for Nutrition.

40 CFR 1508.14 - Human environment.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Human environment. 1508.14 Section 1508.14 Protection of Environment COUNCIL ON ENVIRONMENTAL QUALITY TERMINOLOGY AND INDEX § 1508.14 Human environment. Human environment shall be interpreted comprehensively to include the natural and...

The gut microbiota, obesity and insulin resistance.

Science.gov (United States)

Shen, Jian; Obin, Martin S; Zhao, Liping

2013-02-01

The human gut is densely populated by commensal and symbiotic microbes (the "gut microbiota"), with the majority of the constituent microorganisms being bacteria. Accumulating evidence indicates that the gut microbiota plays a significant role in the development of obesity, obesity-associated inflammation and insulin resistance. In this review we discuss molecular and cell biological mechanisms by which the microbiota participate in host functions that impact the development and maintenance of the obese state, including host ingestive behavior, energy harvest, energy expenditure and fat storage. We additionally explore the diverse signaling pathways that regulate gut permeability and bacterial translocation to the host and how these are altered in the obese state to promote the systemic inflammation ("metabolic endotoxemia") that is a hallmark of obesity and its complications. Fundamental to our discussions is the concept of "crosstalk", i.e., the biochemical exchange between host and microbiota that maintains the metabolic health of the superorganism and whose dysregulation is a hallmark of the obese state. Differences in community composition, functional genes and metabolic activities of the gut microbiota appear to distinguish lean vs obese individuals, suggesting that gut 'dysbiosis' contributes to the development of obesity and/or its complications. The current challenge is to determine the relative importance of obesity-associated compositional and functional changes in the microbiota and to identify the relevant taxa and functional gene modules that promote leanness and metabolic health. As diet appears to play a predominant role in shaping the microbiota and promoting obesity-associated dysbiosis, parallel initiatives are required to elucidate dietary patterns and diet components (e.g., prebiotics, probiotics) that promote healthy gut microbiota. How the microbiota promotes human health and disease is a rich area of investigation that is likely to generate

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.

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.

Mycotoxin: Its Impact on Gut Health and Microbiota

Science.gov (United States)

Liew, Winnie-Pui-Pui; Mohd-Redzwan, Sabran

2018-01-01

The secondary metabolites produced by fungi known as mycotoxins, are capable of causing mycotoxicosis (diseases and death) in human and animals. Contamination of feedstuffs as well as food commodities by fungi occurs frequently in a natural manner and is accompanied by the presence of mycotoxins. The occurrence of mycotoxins' contamination is further stimulated by the on-going global warming as reflected in some findings. This review comprehensively discussed the role of mycotoxins (trichothecenes, zearalenone, fumonisins, ochratoxins, and aflatoxins) toward gut health and gut microbiota. Certainly, mycotoxins cause perturbation in the gut, particularly in the intestinal epithelial. Recent insights have generated an entirely new perspective where there is a bi-directional relationship exists between mycotoxins and gut microbiota, thus suggesting that our gut microbiota might be involved in the development of mycotoxicosis. The bacteria–xenobiotic interplay for the host is highlighted in this review article. It is now well established that a healthy gut microbiota is largely responsible for the overall health of the host. Findings revealed that the gut microbiota is capable of eliminating mycotoxin from the host naturally, provided that the host is healthy with a balance gut microbiota. Moreover, mycotoxins have been demonstrated for modulation of gut microbiota composition, and such alteration in gut microbiota can be observed up to species level in some of the studies. Most, if not all, of the reported effects of mycotoxins, are negative in terms of intestinal health, where beneficial bacteria are eliminated accompanied by an increase of the gut pathogen. The interactions between gut microbiota and mycotoxins have a significant role in the development of mycotoxicosis, particularly hepatocellular carcinoma. Such knowledge potentially drives the development of novel and innovative strategies for the prevention and therapy of mycotoxin contamination and

Mycotoxin: Its Impact on Gut Health and Microbiota

Directory of Open Access Journals (Sweden)

Winnie-Pui-Pui Liew

2018-02-01

Full Text Available The secondary metabolites produced by fungi known as mycotoxins, are capable of causing mycotoxicosis (diseases and death in human and animals. Contamination of feedstuffs as well as food commodities by fungi occurs frequently in a natural manner and is accompanied by the presence of mycotoxins. The occurrence of mycotoxins' contamination is further stimulated by the on-going global warming as reflected in some findings. This review comprehensively discussed the role of mycotoxins (trichothecenes, zearalenone, fumonisins, ochratoxins, and aflatoxins toward gut health and gut microbiota. Certainly, mycotoxins cause perturbation in the gut, particularly in the intestinal epithelial. Recent insights have generated an entirely new perspective where there is a bi-directional relationship exists between mycotoxins and gut microbiota, thus suggesting that our gut microbiota might be involved in the development of mycotoxicosis. The bacteria–xenobiotic interplay for the host is highlighted in this review article. It is now well established that a healthy gut microbiota is largely responsible for the overall health of the host. Findings revealed that the gut microbiota is capable of eliminating mycotoxin from the host naturally, provided that the host is healthy with a balance gut microbiota. Moreover, mycotoxins have been demonstrated for modulation of gut microbiota composition, and such alteration in gut microbiota can be observed up to species level in some of the studies. Most, if not all, of the reported effects of mycotoxins, are negative in terms of intestinal health, where beneficial bacteria are eliminated accompanied by an increase of the gut pathogen. The interactions between gut microbiota and mycotoxins have a significant role in the development of mycotoxicosis, particularly hepatocellular carcinoma. Such knowledge potentially drives the development of novel and innovative strategies for the prevention and therapy of mycotoxin

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.

Bacterial communities in termite fungus combs are comprised of consistent gut deposits and contributions from the environment

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Otani, Saria; Hansen, Lars Hestbjerg; Sørensen, Søren J

2016-01-01

, Actinobacteria, and Candidate division TM7 jointly accounting for 92 % of the reads. Analyses of gut microbiotas from 25 of the 33 colonies showed that dominant fungus comb taxa originate from the termite gut. While gut communities were consistent between 2011 and 2013, comb community compositions shifted over...

Long-term Hg pollution-induced structural shifts of bacterial community in the terrestrial isopod (Porcellio scaber) gut

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Lapanje, Ales, E-mail: ales@ifb.s [Institute of Physical Biology, Ljubljana (Slovenia); Zrimec, Alexis [Institute of Physical Biology, Ljubljana (Slovenia); Drobne, Damjana [Department of Biology, Biotechnical Faculty, University of Ljubljana, Ljubljana (Slovenia); Rupnik, Maja [Institute of Public Health Maribor, Maribor (Slovenia)

2010-10-15

In previous studies we detected lower species richness and lower Hg sensitivity of the bacteria present in egested guts of Porcellio scaber (Crustacea, Isopoda) from chronically Hg polluted than from unpolluted environment. Basis for such results were further investigated by sequencing of 16S rRNA genes of mercury-resistant (Hg{sup r}) isolates and clone libraries. We observed up to 385 times higher numbers of Hg{sup r} bacteria in guts of animals from polluted than from unpolluted environment. The majority of Hg{sup r} strains contained merA genes. Sequencing of 16S rRNA clones from egested guts of animals from Hg-polluted environments showed elevated number of bacteria from Pseudomonas, Listeria and Bacteroidetes relatives groups. In animals from pristine environment number of bacteria from Achromobacter relatives, Alcaligenes, Paracoccus, Ochrobactrum relatives, Rhizobium/Agrobacterium, Bacillus and Microbacterium groups were elevated. Such bacterial community shifts in guts of animals from Hg-polluted environment could significantly contribute to P. scaber Hg tolerance. - Chronic environmental mercury pollution induces bacterial community shifts and presence of elevated number as well as increased diversity of Hg-resistant bacteria in guts of isopods.

Long-term Hg pollution-induced structural shifts of bacterial community in the terrestrial isopod (Porcellio scaber) gut

International Nuclear Information System (INIS)

Lapanje, Ales; Zrimec, Alexis; Drobne, Damjana; Rupnik, Maja

2010-01-01

In previous studies we detected lower species richness and lower Hg sensitivity of the bacteria present in egested guts of Porcellio scaber (Crustacea, Isopoda) from chronically Hg polluted than from unpolluted environment. Basis for such results were further investigated by sequencing of 16S rRNA genes of mercury-resistant (Hg r ) isolates and clone libraries. We observed up to 385 times higher numbers of Hg r bacteria in guts of animals from polluted than from unpolluted environment. The majority of Hg r strains contained merA genes. Sequencing of 16S rRNA clones from egested guts of animals from Hg-polluted environments showed elevated number of bacteria from Pseudomonas, Listeria and Bacteroidetes relatives groups. In animals from pristine environment number of bacteria from Achromobacter relatives, Alcaligenes, Paracoccus, Ochrobactrum relatives, Rhizobium/Agrobacterium, Bacillus and Microbacterium groups were elevated. Such bacterial community shifts in guts of animals from Hg-polluted environment could significantly contribute to P. scaber Hg tolerance. - Chronic environmental mercury pollution induces bacterial community shifts and presence of elevated number as well as increased diversity of Hg-resistant bacteria in guts of isopods.

Assessing the Influence of Vegan, Vegetarian and Omnivore Oriented Westernized Dietary Styles on Human Gut Microbiota: A Cross Sectional Study

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Carmen Losasso

2018-03-01

Full Text Available Diet and lifestyle have a strong influence on gut microbiota, which in turn has important implications on a variety of health-related aspects. Despite great advances in the field, it remains unclear to which extent the composition of the gut microbiota is modulated by the intake of animal derived products, compared to a vegetable based diet. Here the specific impact of vegan, vegetarian, and omnivore feeding type on the composition of gut microbiota of 101 adults was investigated among groups homogeneous for variables known to have a role in modulating gut microbial composition such as age, anthropometric variables, ethnicity, and geographic area. The results displayed a picture where the three different dietetic profiles could be well distinguished on the basis of participant’s dietetic regimen. Regarding the gut microbiota; vegetarians had a significantly greater richness compared to omnivorous. Moreover, counts of Bacteroidetes related operational taxonomic units (OTUs were greater in vegans and vegetarians compared to omnivores. Interestingly considering the whole bacterial community composition the three cohorts were unexpectedly similar, which is probably due to their common intake in terms of nutrients rather than food, e.g., high fat content and reduced protein and carbohydrate intake. This finding suggests that fundamental nutritional choices such as vegan, vegetarian, or omnivore do influence the microbiota but do not allow to infer conclusions on gut microbial composition, and suggested the possibility for a preferential impact of other variables, probably related to the general life style on shaping human gut microbial community in spite of dietary influence. Consequently, research were individuals are categorized on the basis of their claimed feeding types is of limited use for scientific studies, since it appears to be oversimplified.

Early Development of the Gut Microbiota and Immune Health

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M. Pilar Francino

2014-09-01

Full Text Available In recent years, the increase in human microbiome research brought about by the rapidly evolving “omic” technologies has established that the balance among the microbial groups present in the human gut, and their multipronged interactions with the host, are crucial for health. On the other hand, epidemiological and experimental support has also grown for the ‘early programming hypothesis’, according to which factors that act in utero and early in life program the risks for adverse health outcomes later on. The microbiota of the gut develops during infancy, in close interaction with immune development, and with extensive variability across individuals. It follows that the specific process of gut colonization and the microbe-host interactions established in an individual during this period have the potential to represent main determinants of life-long propensity to immune disease. Although much remains to be learnt on the progression of events by which the gut microbiota becomes established and initiates its intimate relationships with the host, and on the long-term repercussions of this process, recent works have advanced significatively in this direction.

Mucosal T cells in gut homeostasis and inflammation

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van Wijk, Femke; Cheroutre, Hilde

2010-01-01

The antigen-rich environment of the gut interacts with a highly integrated and specialized mucosal immune system that has the challenging task of preventing invasion and the systemic spread of microbes, while avoiding excessive or unnecessary immune responses to innocuous antigens. Disruption of the mucosal barrier and/or defects in gut immune regulatory networks may lead to chronic intestinal inflammation as seen in inflammatory bowel disease. The T-cell populations of the intestine play a c...

[Diet and gut microbiota: two sides of the same coin?

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Schiumerini, Ramona; Pasqui, Francesca; Festi, Davide

2018-01-01

Gut microbiota is a complex ecosystem, resident in the digestive tract, exerting multiple functions that can have a significant impact on the pathophysiology of the host organism. The composition and functions of this "superorganism" are influenced by many factors, and among them, the host's dietary habits seem to have a significant effect. Dietary changes in the evolution of human history and in the different stages of life of the human subjects are responsible for qualitative and functional modification of gut microbiota. At the same time, the different dietary models adopted in worldwide geographic areas take into account the inter-individual differences concerning composition and microbial function. This close relationship between diet, gut microbiota and host seems, in fact, to be responsible for the protection or predisposition to develop several metabolic, immunological, neoplastic and functional diseases. Thus, several studies have evaluated the impact of diet and lifestyle modification strategies on gut microbiota composition and functions which, in turn, seems to affect the effectiveness of such therapeutic measures. Gut microbiota manipulation strategies, as complementary to dietary modifications, represent a fascinating field of research, even if consolidated data are still lacking.

Intestinal Immunomodulatory Cells (T Lymphocytes: A Bridge between Gut Microbiota and Diabetes

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Qingwei Li

2018-01-01

Full Text Available Diabetes mellitus (DM is one of the most familiar chronic diseases threatening human health. Recent studies have shown that the development of diabetes is closely related to an imbalance of the gut microbiota. Accordingly, there is increasing interest in how changes in the gut microbiota affect diabetes and its underlying mechanisms. Immunomodulatory cells play important roles in maintaining the normal functioning of the human immune system and in maintaining homeostasis. Intestinal immunomodulatory cells (IICs are located in the intestinal mucosa and are regarded as an intermediary by which the gut microbiota affects physiological and pathological properties. Diabetes can be regulated by IICs, which act as a bridge linking the gut microbiota and DM. Understanding this bridge role of IICs may clarify the mechanisms by which the gut microbiota contributes to DM. Based on recent research, we summarize this process, thereby providing a basis for further studies of diabetes and other similar immune-related diseases.

The gut microbiota and obesity: from correlation to causality.

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Zhao, Liping

2013-09-01

The gut microbiota has been linked with chronic diseases such as obesity in humans. However, the demonstration of causality between constituents of the microbiota and specific diseases remains an important challenge in the field. In this Opinion article, using Koch's postulates as a conceptual framework, I explore the chain of causation from alterations in the gut microbiota, particularly of the endotoxin-producing members, to the development of obesity in both rodents and humans. I then propose a strategy for identifying the causative agents of obesity in the human microbiota through a combination of microbiome-wide association studies, mechanistic analysis of host responses and the reproduction of diseases in gnotobiotic animals.

Impact of the gut microbiota on rodent models of human disease.

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Hansen, Axel Kornerup; Hansen, Camilla Hartmann Friis; Krych, Lukasz; Nielsen, Dennis Sandris

2014-12-21

Traditionally bacteria have been considered as either pathogens, commensals or symbionts. The mammal gut harbors 10(14) organisms dispersed on approximately 1000 different species. Today, diagnostics, in contrast to previous cultivation techniques, allow the identification of close to 100% of bacterial species. This has revealed that a range of animal models within different research areas, such as diabetes, obesity, cancer, allergy, behavior and colitis, are affected by their gut microbiota. Correlation studies may for some diseases show correlation between gut microbiota composition and disease parameters higher than 70%. Some disease phenotypes may be transferred when recolonizing germ free mice. The mechanistic aspects are not clear, but some examples on how gut bacteria stimulate receptors, metabolism, and immune responses are discussed. A more deeper understanding of the impact of microbiota has its origin in the overall composition of the microbiota and in some newly recognized species, such as Akkermansia muciniphila, Segmented filamentous bacteria and Faecalibacterium prausnitzii, which seem to have an impact on more or less severe disease in specific models. Thus, the impact of the microbiota on animal models is of a magnitude that cannot be ignored in future research. Therefore, either models with specific microbiota must be developed, or the microbiota must be characterized in individual studies and incorporated into data evaluation.

Gut Microbiota-brain Axis

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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.

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

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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

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

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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.

CoMiniGut-a small volume in vitro colon model for the screening of gut microbial fermentation processes.

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Wiese, Maria; Khakimov, Bekzod; Nielsen, Sebastian; Sørensen, Helena; van den Berg, Frans; Nielsen, Dennis Sandris

2018-01-01

Driven by the growing recognition of the influence of the gut microbiota (GM) on human health and disease, there is a rapidly increasing interest in understanding how dietary components, pharmaceuticals and pre- and probiotics influence GM. In vitro colon models represent an attractive tool for this purpose. With the dual objective of facilitating the investigation of rare and expensive compounds, as well as an increased throughput, we have developed a prototype in vitro parallel gut microbial fermentation screening tool with a working volume of only 5 ml consisting of five parallel reactor units that can be expanded with multiples of five to increase throughput. This allows e.g., the investigation of interpersonal variations in gut microbial dynamics and the acquisition of larger data sets with enhanced statistical inference. The functionality of the in vitro colon model, Copenhagen MiniGut (CoMiniGut) was first demonstrated in experiments with two common prebiotics using the oligosaccharide inulin and the disaccharide lactulose at 1% (w/v). We then investigated fermentation of the scarce and expensive human milk oligosaccharides (HMOs) 3-Fucosyllactose, 3-Sialyllactose, 6-Sialyllactose and the more common Fructooligosaccharide in fermentations with infant gut microbial communities. Investigations of microbial community composition dynamics in the CoMiniGut reactors by MiSeq-based 16S rRNA gene amplicon high throughput sequencing showed excellent experimental reproducibility and allowed us to extract significant differences in gut microbial composition after 24 h of fermentation for all investigated substrates and fecal donors. Furthermore, short chain fatty acids (SCFAs) were quantified for all treatments and donors. Fermentations with inulin and lactulose showed that inulin leads to a microbiota dominated by obligate anaerobes, with high relative abundance of Bacteroidetes, while the more easily fermented lactulose leads to higher relative abundance of

Alterations of the Gut Microbiome in Hypertension

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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

Leaky Gut As a Danger Signal for Autoimmune Diseases

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Qinghui Mu

2017-05-01

Full Text Available The intestinal epithelial lining, together with factors secreted from it, forms a barrier that separates the host from the environment. In pathologic conditions, the permeability of the epithelial lining may be compromised allowing the passage of toxins, antigens, and bacteria in the lumen to enter the blood stream creating a “leaky gut.” In individuals with a genetic predisposition, a leaky gut may allow environmental factors to enter the body and trigger the initiation and development of autoimmune disease. Growing evidence shows that the gut microbiota is important in supporting the epithelial barrier and therefore plays a key role in the regulation of environmental factors that enter the body. Several recent reports have shown that probiotics can reverse the leaky gut by enhancing the production of tight junction proteins; however, additional and longer term studies are still required. Conversely, pathogenic bacteria that can facilitate a leaky gut and induce autoimmune symptoms can be ameliorated with the use of antibiotic treatment. Therefore, it is hypothesized that modulating the gut microbiota can serve as a potential method for regulating intestinal permeability and may help to alter the course of autoimmune diseases in susceptible individuals.

Gut DNA viromes of Malawian twins discordant for severe acute malnutrition

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The bacterial component of the human gut microbiota undergoes a definable program of postnatal development. Evidence is accumulating that this program is disrupted in children with severe acute malnutrition (SAM) and that their persistent gut microbiota immaturity, which is not durably repaired with...

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

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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.

Commensal Homeostasis of Gut Microbiota-Host for the Impact of Obesity

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Pengyi Zhang

2018-01-01

Full Text Available Gut microbiota and their metabolites have been linked to a series of chronic diseases such as obesity and other metabolic dysfunctions. Obesity is an increasingly serious international health issue that may lead to a risk of insulin resistance and other metabolic diseases. The relationship between gut microbiota and the host is both interdependent and relatively independent. In this review, the causality of gut microbiota and its role in the pathogenesis and intervention of obesity is comprehensively presented to include human genotype, enterotypes, interactions of gut microbiota with the host, microbial metabolites, and energy homeostasis all of which may be influenced by dietary nutrition. Diet can enhance, inhibit, or even change the composition and functions of the gut microbiota. The metabolites they produce depend upon the dietary substrates provided, some of which have indispensable functions for the host. Therefore, diet is a key factor that maintains or not a healthy commensal relationship. In addition, the specific genotype of the host may impact the phylogenetic compositions of gut microbiota through the production of host metabolites. The commensal homeostasis of gut microbiota is favored by a balance of microbial composition, metabolites, and energy. Ultimately the desired commensal relationship is one of mutual support. This article analyzes the clues that result in patterns of commensal homeostasis. A deeper understanding of these interactions is beneficial for developing effective prevention, diagnosis, and personalized therapeutic strategies to combat obesity and other metabolic diseases. The idea we discuss is meant to improve human health by shaping or modulating the beneficial gut microbiota.

Role of human gut microbiota metabolism in the anti-inflammatory effect of traditionally used ellagitannin-rich plant materials.

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Piwowarski, Jakub P; Granica, Sebastian; Zwierzyńska, Marta; Stefańska, Joanna; Schopohl, Patrick; Melzig, Matthias F; Kiss, Anna K

2014-08-08

Ellagitannin-rich plant materials are widely used in traditional medicine as effective, internally used anti-inflammatory agents. Due to the not well-established bioavailability of ellagitannins, the mechanisms of observed therapeutic effects following oral administration still remain unclear. The aim of the study was to evaluate if selected ellagitannin-rich plant materials could be the source of bioavailable gut microbiota metabolites, i.e. urolithins, together with determination of the anti-inflammatory activity of the metabolites produced on the THP-1 cell line derived macrophages model. The formation of urolithins was determined by ex vivo incubation of human fecal samples with aqueous extracts from selected plant materials. The anti-inflammatory activity study of metabolites was determined on PMA differentiated, IFN-γ and LPS stimulated, human THP-1 cell line-derived macrophages. The formation of urolithin A, B and C by human gut microbiota was established for aqueous extracts from Filipendula ulmaria (L.) Maxim. herb (Ph. Eur.), Geranium pratense L. herb, Geranium robertianum L. herb, Geum urbanum L. root and rhizome, Lythrum salicaria L. herb (Ph. Eur.), Potentilla anserina L. herb, Potentilla erecta (L.) Raeusch rhizome (Ph. Eur.), Quercus robur L. bark (Ph. Eur.), Rubus idaeus L. leaf, Rubus fruticosus L. and pure ellagitannin vescalagin. Significant inhibition of TNF-α production was determined for all urolithins, while for the most potent urolithin A inhibition was observed at nanomolar concentrations (at 0.625 μM 29.2±6.4% of inhibition). Urolithin C was the only compound inhibiting IL-6 production (at 0.625 μM 13.9±2.2% of inhibition). The data obtained clearly indicate that in the case of peroral use of the examined ellagitannin-rich plant materials the bioactivity of gut microbiota metabolites, i.e. urolithins, has to be taken under consideration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Bacterial adaptation to the gut environment favors successful colonization: microbial and metabonomic characterization of a simplified microbiota mouse model.

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Rezzonico, Enea; Mestdagh, Renaud; Delley, Michèle; Combremont, Séverine; Dumas, Marc-Emmanuel; Holmes, Elaine; Nicholson, Jeremy; Bibiloni, Rodrigo

2011-01-01

Rodent models harboring a simple yet functional human intestinal microbiota provide a valuable tool to study the relationships between mammals and their bacterial inhabitants. In this study, we aimed to develop a simplified gnotobiotic mouse model containing 10 easy-to-grow bacteria, readily available from culture repositories, and of known genome sequence, that overall reflect the dominant commensal bacterial makeup found in adult human feces. We observed that merely inoculating a mix of fresh bacterial cultures into ex-germ free mice did not guarantee a successful intestinal colonization of the entire bacterial set, as mice inoculated simultaneously with all strains only harbored 3 after 21 d. Therefore, several inoculation procedures were tested and levels of individual strains were quantified using molecular tools. Best results were obtained by inoculating single bacterial strains into individual animals followed by an interval of two weeks before allowing the animals to socialize to exchange their commensal microbes. Through this procedure, animals were colonized with almost the complete bacterial set (9/10). Differences in the intestinal composition were also reflected in the urine and plasma metabolic profiles, where changes in lipids, SCFA, and amino acids were observed. We conclude that adaptation of bacterial strains to the host's gut environment (mono-colonization) may predict a successful establishment of a more complex microbiota in rodents.

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

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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.

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

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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.

Host immunostimulation and substrate utilization of the gut symbiont Akkermansia muciniphila

NARCIS (Netherlands)

Ottman, N.A.

2015-01-01

Host immunostimulation and substrate utilization of the gut symbiont Akkermansia muciniphila

Noora A. Ottman

The human gastrointestinal tract is colonized by a complex community of micro-organisms, the gut microbiota. The majority of these

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

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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...

The Reciprocal Interactions between Polyphenols and Gut Microbiota and Effects on Bioaccessibility

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Ozdal, Tugba; Sela, David A.; Xiao, Jianbo; Boyacioglu, Dilek; Chen, Fang; Capanoglu, Esra

2016-01-01

As of late, polyphenols have increasingly interested the scientific community due to their proposed health benefits. Much of this attention has focused on their bioavailability. Polyphenol–gut microbiota interactions should be considered to understand their biological functions. The dichotomy between the biotransformation of polyphenols into their metabolites by gut microbiota and the modulation of gut microbiota composition by polyphenols contributes to positive health outcomes. Although there are many studies on the in vivo bioavailability of polyphenols, the mutual relationship between polyphenols and gut microbiota is not fully understood. This review focuses on the biotransformation of polyphenols by gut microbiota, modulation of gut microbiota by polyphenols, and the effects of these two-way mutual interactions on polyphenol bioavailability, and ultimately, human health. PMID:26861391

HLA-B27 and human β2-microglobulin affect the gut microbiota of transgenic rats.

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Phoebe Lin

Full Text Available The HLA-B27 gene is a major risk factor for clinical diseases including ankylosing spondylitis, acute anterior uveitis, reactive arthritis, and psoriatic arthritis, but its mechanism of risk enhancement is not completely understood. The gut microbiome has recently been shown to influence several HLA-linked diseases. However, the role of HLA-B27 in shaping the gut microbiome has not been previously investigated. In this study, we characterize the differences in the gut microbiota mediated by the presence of the HLA-B27 gene. We identified differences in the cecal microbiota of Lewis rats transgenic for HLA-B27 and human β2-microglobulin (hβ2m, compared with wild-type Lewis rats, using biome representational in situ karyotyping (BRISK and 16S rRNA gene sequencing. 16S sequencing revealed significant differences between transgenic animals and wild type animals by principal coordinates analysis. Further analysis of the data set revealed an increase in Prevotella spp. and a decrease in Rikenellaceae relative abundance in the transgenic animals compared to the wild type animals. By BRISK analysis, species-specific differences included an increase in Bacteroides vulgatus abundance in HLA-B27/hβ2m and hβ2m compared to wild type rats. The finding that HLA-B27 is associated with altered cecal microbiota has not been shown before and can potentially provide a better understanding of the clinical diseases associated with this gene.

Gut microbiota: the next-gen frontier in preventive and therapeutic medicine?

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Ravinder eNagpal

2014-06-01

Full Text Available Our gut harbors an extremely diverse collection of trillions of microbes that, besides degrading the complex dietary constituents, execute numerous activities vital for our metabolism and immune health. Although the importance of gut microbiota in maintaining digestive health has long been believed, its close correlation with numerous chronic ailments has recently been exposed, thanks to the innovative mechanistic studies on the compositional and functional aspects of gut microbial communities using germ-free or humanized animal models. Since a myriad of mysteries about the precise structures and functions of gut microbial communities in specific health situations still remains to be explicated, the emerging field of gut microbiota remains a foremost objective of research for microbiologists, computational biologists, clinicians, nutritionalists etc. Nevertheless, it is only after a comprehensive understanding of the structure, density and function of the gut microbiota that the new therapeutic targets could be captured and utilized for a healthier gut as well as overall wellbeing.

The human gut microbiota: metabolism and perspective in obesity.

Science.gov (United States)

Gomes, Aline Corado; Hoffmann, Christian; Mota, João Felipe

2018-04-18

The gut microbiota has been recognized as an important factor in the development of metabolic diseases such as obesity and is considered an endocrine organ involved in the maintenance of energy homeostasis and host immunity. Dysbiosis can change the functioning of the intestinal barrier and the gut-associated lymphoid tissues (GALT) by allowing the passage of structural components of bacteria, such as lipopolysaccharides (LPS), which activate inflammatory pathways that may contribute to the development of insulin resistance. Furthermore, intestinal dysbiosis can alter the production of gastrointestinal peptides related to satiety, resulting in an increased food intake. In obese people, this dysbiosis seems be related to increases of the phylum Firmicutes, the genus Clostridium, and the species Eubacterium rectale, Clostridium coccoides, Lactobacillus reuteri, Akkermansia muciniphila, Clostridium histolyticum, and Staphylococcus aureus.

Interplay between gut microbiota, its metabolites and human metabolism: Dissecting cause from consequence

NARCIS (Netherlands)

Hartstra, A. V.; Nieuwdorp, M.; Herrema, H.

2016-01-01

Background: Alterations in gut microbiota composition and bacterial metabolites have been increasingly recognized to affect host metabolism and are at the basis of metabolic diseases such as obesity and type 2 diabetes (DM2). Intestinal enteroendocrine cells (EEC's) sense gut luminal content and

The Potential for Gut Organoid Derived Interstitial Cells of Cajal in Replacement Therapy

Directory of Open Access Journals (Sweden)

Jerry Zhou

2017-09-01

Full Text Available Effective digestion requires propagation of food along the entire length of the gastrointestinal tract. This process involves coordinated waves of peristalsis produced by enteric neural cell types, including different categories of interstitial cells of Cajal (ICC. Impaired food transport along the gastrointestinal tract, either too fast or too slow, causes a range of gut motility disorders that affect millions of people worldwide. Notably, loss of ICC has been shown to affect gut motility. Patients that suffer from gut motility disorders regularly experience diarrhoea and/or constipation, insomnia, anxiety, attention lapses, irritability, dizziness, and headaches that greatly affect both physical and mental health. Limited treatment options are available for these patients, due to the scarcity of human gut tissue for research and transplantation. Recent advances in stem cell technology suggest that large amounts of rudimentary, yet functional, human gut tissue can be generated in vitro for research applications. Intriguingly, these stem cell-derived gut organoids appear to contain functional ICC, although their frequency and functional properties are yet to be fully characterised. By reviewing methods of gut organoid generation, together with what is known of the molecular and functional characteristics of ICC, this article highlights short- and long-term goals that need to be overcome in order to develop ICC-based therapies for gut motility disorders.

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....

Mobile Robots in Human Environments

DEFF Research Database (Denmark)

Svenstrup, Mikael

intelligent mobile robotic devices capable of being a more natural and sociable actor in a human environment. More specific the emphasis is on safe and natural motion and navigation issues. First part of the work focus on developing a robotic system, which estimates human interest in interacting......, lawn mowers, toy pets, or as assisting technologies for care giving. If we want robots to be an even larger and more integrated part of our every- day environments, they need to become more intelligent, and behave safe and natural to the humans in the environment. This thesis deals with making...... as being able to navigate safely around one person, the robots must also be able to navigate in environments with more people. This can be environments such as pedestrian streets, hospital corridors, train stations or airports. The developed human-aware navigation strategy is enhanced to formulate...