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Sample records for human gut flora

  1. Geographic differences in digoxin inactivation, a metabolic activity of the human anaerobic gut flora.

    PubMed Central

    Mathan, V I; Wiederman, J; Dobkin, J F; Lindenbaum, J

    1989-01-01

    The inactivation of digoxin by conversion to reduced metabolites (digoxin reduction products, or DRP), a function of the anaerobic gut flora, was studied in normal volunteers from southern India and the United States. Digoxin was metabolised to DRP by 28 (13.7%) of 204 healthy south Indians in contrast to 67 (36.0%) of 186 New Yorkers (p less than 1 X 10(-6)). Only 1.0% of Indians compared with 14.0% of Americans excreted large amounts of metabolites (greater than 40% DRP) in the urine (p less than 1 X 10(-5)). Of 104 urban Indians, 23 (22.1%) were metabolisers, in contrast with five of 100 rural villagers (p less than 0.001). Within the urban group, digoxin metabolism correlated with education, frequency of animal protein intake, and most significantly, personal income. Organisms capable of reducing digoxin in vitro were found with similar frequencies in stool cultures from Indians and Americans. In the cultures of some subjects, DRP production was inhibited at lower dilutions but expressed at higher dilutions. We conclude that variations in drug metabolism between population groups may result from differences in the metabolic activity of the anaerobic gut flora probably mediated by environmentally determined factors. PMID:2759492

  2. [Multiple Sclerosis and Commensal Gut Flora].

    PubMed

    Yamamura, Takashi

    2016-06-01

    Although a symbiotic relationship between commensal gut microbiota and host is widely appreciated, recent works have indicated that normal gut flora functions to prevent inflammatory bowel diseases and obesity in the host, indicating a more mutualistic relationship. Dysbiosis of the commensal flora may lead to development of these disorders. Studies using experimental auto immune encephalomyelitis (EAE), a rodent model for studying multiple sclerosis (MS), revealed that onset of MS may be triggered by dysbiosis in the gut. We recently revealed a significant reduction in certain clostridia strains, which probably function to induce regulatory T cells, in the gut microbiota of patients with MS. Results from this study should be consideved when designing strategies for the prevention and treatment of MS. PMID:27279159

  3. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow.

    PubMed

    Kim, Hyun Jung; Huh, Dongeun; Hamilton, Geraldine; Ingber, Donald E

    2012-06-21

    Development of an in vitro living cell-based model of the intestine that mimics the mechanical, structural, absorptive, transport and pathophysiological properties of the human gut along with its crucial microbial symbionts could accelerate pharmaceutical development, and potentially replace animal testing. Here, we describe a biomimetic 'human gut-on-a-chip' microdevice composed of two microfluidic channels separated by a porous flexible membrane coated with extracellular matrix (ECM) and lined by human intestinal epithelial (Caco-2) cells that mimics the complex structure and physiology of living intestine. The gut microenvironment is recreated by flowing fluid at a low rate (30 μL h(-1)) producing low shear stress (0.02 dyne cm(-2)) over the microchannels, and by exerting cyclic strain (10%; 0.15 Hz) that mimics physiological peristaltic motions. Under these conditions, a columnar epithelium develops that polarizes rapidly, spontaneously grows into folds that recapitulate the structure of intestinal villi, and forms a high integrity barrier to small molecules that better mimics whole intestine than cells in cultured in static Transwell models. In addition, a normal intestinal microbe (Lactobacillus rhamnosus GG) can be successfully co-cultured for extended periods (>1 week) on the luminal surface of the cultured epithelium without compromising epithelial cell viability, and this actually improves barrier function as previously observed in humans. Thus, this gut-on-a-chip recapitulates multiple dynamic physical and functional features of human intestine that are critical for its function within a controlled microfluidic environment that is amenable for transport, absorption, and toxicity studies, and hence it should have great value for drug testing as well as development of novel intestinal disease models. PMID:22434367

  4. Healthy human gut phageome.

    PubMed

    Manrique, Pilar; Bolduc, Benjamin; Walk, Seth T; van der Oost, John; de Vos, Willem M; Young, Mark J

    2016-09-13

    The role of bacteriophages in influencing the structure and function of the healthy human gut microbiome is unknown. With few exceptions, previous studies have found a high level of heterogeneity in bacteriophages from healthy individuals. To better estimate and identify the shared phageome of humans, we analyzed a deep DNA sequence dataset of active bacteriophages and available metagenomic datasets of the gut bacteriophage community from healthy individuals. We found 23 shared bacteriophages in more than one-half of 64 healthy individuals from around the world. These shared bacteriophages were found in a significantly smaller percentage of individuals with gastrointestinal/irritable bowel disease. A network analysis identified 44 bacteriophage groups of which 9 (20%) were shared in more than one-half of all 64 individuals. These results provide strong evidence of a healthy gut phageome (HGP) in humans. The bacteriophage community in the human gut is a mixture of three classes: a set of core bacteriophages shared among more than one-half of all people, a common set of bacteriophages found in 20-50% of individuals, and a set of bacteriophages that are either rarely shared or unique to a person. We propose that the core and common bacteriophage communities are globally distributed and comprise the HGP, which plays an important role in maintaining gut microbiome structure/function and thereby contributes significantly to human health. PMID:27573828

  5. Systematic analysis of the association between gut flora and obesity through high-throughput sequencing and bioinformatics approaches.

    PubMed

    Chiu, Chih-Min; Huang, Wei-Chih; Weng, Shun-Long; Tseng, Han-Chi; Liang, Chao; Wang, Wei-Chi; Yang, Ting; Yang, Tzu-Ling; Weng, Chen-Tsung; Chang, Tzu-Hao; Huang, Hsien-Da

    2014-01-01

    Eighty-one stool samples from Taiwanese were collected for analysis of the association between the gut flora and obesity. The supervised analysis showed that the most, abundant genera of bacteria in normal samples (from people with a body mass index (BMI) ≤ 24) were Bacteroides (27.7%), Prevotella (19.4%), Escherichia (12%), Phascolarctobacterium (3.9%), and Eubacterium (3.5%). The most abundant genera of bacteria in case samples (with a BMI ≥ 27) were Bacteroides (29%), Prevotella (21%), Escherichia (7.4%), Megamonas (5.1%), and Phascolarctobacterium (3.8%). A principal coordinate analysis (PCoA) demonstrated that normal samples were clustered more compactly than case samples. An unsupervised analysis demonstrated that bacterial communities in the gut were clustered into two main groups: N-like and OB-like groups. Remarkably, most normal samples (78%) were clustered in the N-like group, and most case samples (81%) were clustered in the OB-like group (Fisher's P  value = 1.61E - 07). The results showed that bacterial communities in the gut were highly associated with obesity. This is the first study in Taiwan to investigate the association between human gut flora and obesity, and the results provide new insights into the correlation of bacteria with the rising trend in obesity.

  6. Increased survival in experimental dog heatstroke after reduction of gut flora.

    PubMed

    Bynum, G; Brown, J; Dubose, D; Marsili, M; Leav, I; Pistole, T G; Hamlet, M; LeMaire, M; Caleb, B

    1979-08-01

    A study was undertaken to determine if gut flora contribute to the pathophysiology of experimental canine heatstroke. Fifty animals in four groups were anesthetized with sodium pentobarbital (25 mg/kg) intravenously. An air temperature of 42-46 degrees C was maintained adjacent to the dog with a water-heated blanket for approximately 2 h until rectal temperatures rose to 43.5 +/- 0.4 degrees C. Animals were then cooled passively in room air (28 degrees C, 20% RH) until death or until 18 h elapsed, and were euthanized. Reduction of intestine stool and bacterial contents with antibiotics, cathartics, and enemas prior to heatstroke increased the incidence of 18-h survival from 20.0% to 70.6%; antibiotics administered after heatstroke did not alter the incidence of survival over control values. These data suggest that gut flora, presumably through endotoxemia, contribute to the evolution of heatstroke pathophysiology.

  7. Targeting gut flora to prevent progression of hepatocellular carcinoma.

    PubMed

    Darnaud, Marion; Faivre, Jamila; Moniaux, Nicolas

    2013-02-01

    Increased translocation of intestinal bacteria is a hallmark of chronic liver disease and contributes to hepatic inflammation and fibrosis. Here we tested the hypothesis that the intestinal microbiota and Toll-like receptors (TLRs) promote hepatocellular carcinoma(HCC), a long-term consequence of chronic liver injury, inflammation,and fibrosis. Hepatocarcinogenesis in chronically injured livers depended on the intestinal microbiota and TLR4 activation in nonbone-marrow-derived resident liver cells. TLR4 and the intestinal microbiota were not required for HCC initiation but for HCC promotion, mediating increased proliferation, expression of the hepatomitogen epiregulin, and prevention of apoptosis. Gut sterilization restricted to late stages of hepatocarcinogenesis reduced HCC, suggesting that the intestinal microbiota and TLR4 represent therapeutic targets for HCC prevention in advanced liver disease.

  8. The Human Gut Microbiota.

    PubMed

    Harmsen, Hermie J M; de Goffau, Marcus C

    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 numerous and diverse microbial community present in the gut, especially in the colon, with reported numbers of species that vary between 400 and 1500, for some those we even do not yet have culture representatives.A healthy gut microbiota is important for maintaining a healthy host. An aberrant microbiota can cause diseases of different nature and at different ages ranging from allergies at early age to IBD in young adults. This shows that our gut microbiota needs to be treated well to stay healthy. In this chapter we describe what we consider a healthy microbiota and discuss what the role of the microbiota is in various diseases. Research into these described dysbiosis conditions could lead to new strategies for treatment and/or management of our microbiota to improve health. PMID:27161353

  9. The Human Gut Microbiota.

    PubMed

    Harmsen, Hermie J M; de Goffau, Marcus C

    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 numerous and diverse microbial community present in the gut, especially in the colon, with reported numbers of species that vary between 400 and 1500, for some those we even do not yet have culture representatives.A healthy gut microbiota is important for maintaining a healthy host. An aberrant microbiota can cause diseases of different nature and at different ages ranging from allergies at early age to IBD in young adults. This shows that our gut microbiota needs to be treated well to stay healthy. In this chapter we describe what we consider a healthy microbiota and discuss what the role of the microbiota is in various diseases. Research into these described dysbiosis conditions could lead to new strategies for treatment and/or management of our microbiota to improve health.

  10. Real-time analysis of gut flora in Entamoeba histolytica infected patients of Northern India

    PubMed Central

    2012-01-01

    Background Amebic dysentery is caused by the protozoan parasite Entamoeba histolytica and the ingestion of quadrinucleate cyst of E. histolytica from fecally contaminated food or water initiates infection. Excystation occurs in the lumen of small intestine, where motile and potentially invasive trophozoites germinate from cysts. The ability of trophozoites to interact and digest gut bacteria is apparently important for multiplication of the parasite and its pathogenicity; however the contribution of resident bacterial flora is not well understood. We quantified the population of Bacteroides, Bifidobacterium, Ruminococcus, Lactobacillus, Clostridium leptum subgroup, Clostridium coccoides subgroup, Eubacterium, Campylobacter, Methanobrevibacter smithii and Sulphur reducing bacteria using genus specific primers in healthy (N = 22) vs amebic patients (E. histolytica positive, N = 17) stool samples by Real-time PCR. Results Absolute quantification of Bacteroides (p = .001), Closrtridium coccoides subgroup (p = 0.002), Clostridium leptum subgroup (p = 0.0001), Lactobacillus (p = 0.037), Campylobacter (p = 0.0014) and Eubacterium (p = 0.038) show significant drop in their population however, significant increase in Bifdobacterium (p = 0.009) was observed where as the population of Ruminococcus (p = 0.33) remained unaltered in healthy vs amebic patients (E. histolytica positive). We also report high prevalence of nimE gene in stool samples of both healthy volunteers and amebic patients. No significant decrease in nimE gene copy number was observed before and after the treatment with antiamebic drug. Conclusions Our results show significant alteration in predominant gut bacteria in E. histolytica infected individuals. The frequent episodes of intestinal amoebic dysentery thus result in depletion of few predominant genera in gut that may lead to poor digestion and absorption of food in intestine. It further disturbs the homeostasis

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

    PubMed

    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.

  12. Naturally Occurring Culturable Aerobic Gut Flora of Adult Phlebotomus papatasi, Vector of Leishmania major in the Old World

    PubMed Central

    Mukhopadhyay, Jaba; Braig, Henk R.; Rowton, Edgar D.; Ghosh, Kashinath

    2012-01-01

    Background Cutaneous leishmaniasis is a neglected, vector-borne parasitic disease and is responsible for persistent, often disfiguring lesions and other associated complications. Leishmania, causing zoonotic cutaneous leishmaniasis (ZCL) in the Old World are mainly transmitted by the predominant sand fly vector, Phlebotomus papatasi. To date, there is no efficient control measure or vaccine available for this widespread insect-borne infectious disease. Methodology/Principal Findings A survey was carried out to study the abundance of different natural gut flora in P. papatasi, with the long-term goal of generating a paratransgenic sand fly that can potentially block the development of Leishmania in the sand fly gut, thereby preventing transmission of leishmania in endemic disease foci. Sand flies, in particular, P. papatasi were captured from different habitats of various parts of the world. Gut microbes were cultured and identified using 16S ribosomal DNA analysis and a phylogenetic tree was constructed. We found variation in the species and abundance of gut flora in flies collected from different habitats. However, a few Gram-positive, nonpathogenic bacteria including Bacillus flexus and B. pumilus were common in most of the sites examined. Conclusion/Significance Our results indicate that there is a wide range of variation of aerobic gut flora inhabiting sand fly guts, which possibly reflect the ecological condition of the habitat where the fly breeds. Also, some species of bacteria (B. pumilus, and B. flexus) were found from most of the habitats. Important from an applied perspective of dissemination, our results support a link between oviposition induction and adult gut flora. PMID:22629302

  13. FLORA

    1985-04-01

    FLORA solves, in a 2D domain for the linearized stability of a long-thin (paraxial)axisymmetric equilibrium. This is of interest for determining the magnetohydrodynamic stability of a magnetic mirror plasma confinement system including finite-Larmor radius and rotation effects. An axisymmetric plasma equilibrium is specified by providing pressure profiles, the plasma mass density, the vacuum magnetic fields, and plasma electric potential as functions of (?).

  14. Fusobacterium prausnitzii and related species represent a dominant group within the human fecal flora.

    PubMed

    Suau, A; Rochet, V; Sghir, A; Gramet, G; Brewaeys, S; Sutren, M; Rigottier-Gois, L; Doré, J

    2001-04-01

    The human gut microflora plays a key role in nutrition and health. It has been extensively studied by conventional culture techniques. However these methods are difficult, time consuming and their results not always consistent. Furthermore microscopic counts indicate that only 20 to 40% of the total flora can be cultivated. Among the predominant species of the human gut, Fusobacterium prausnitzii was reported either as one of the most frequent and numerous species or was seldom retrieved. We designed and validated a specific rRNA-targeted oligonucleotide probe, called S-*-Fprau-0645-a-A-23, to accurately detect and quantify F. prausnitzii and relatives within the human fecal microflora. The target group accounted for 5.3 +/- 3% of total bacterial 16S rRNA using dot blot hybridization (10 human fecal samples) and 16.5 +/- 7% of cells stained with Dapi using in situ hybridization (10 other human fecal samples). A specific morphology seemed to be typical and dominant: two cells forming an asymmetrical double droplet. This work showed that F. prausnitzii and phylogenetically related species represent a dominant group within the human fecal flora.

  15. Bacteriotherapy using fecal flora: toying with human motions.

    PubMed

    Borody, Thomas J; Warren, Eloise F; Leis, Sharyn M; Surace, Rosa; Ashman, Ori; Siarakas, Steven

    2004-07-01

    The intestinal flora may play a key role in the pathogenesis of certain gastrointestinal (GI) diseases. Components of bowel flora such as Lactobacillus acidophilus and Bifidobacterium bifidus have long been used empirically as therapeutic agents for GI disorders. More complex combinations of probiotics for therapeutic bacteriotherapy have also recently become available, however the most elaborate mix of human-derived probiotic bacteria is, by definition, the entire fecal flora. Fecal bacteriotherapy uses the complete normal human flora as a therapeutic probiotic mixture of living organisms. This type of bacteriotherapy has a longstanding history in animal health and has been used sporadically against chronic infections of the bowel, especially as a treatment of last resort for patients with severe Clostridium difficile syndromes including recurrent diarrhea, colitis, and pseudomembranous colitis. Encouraging results have also been observed following infusions of human fecal flora in patients with inflammatory bowel disease, irritable bowel syndrome, and chronic constipation. The therapeutic use of fecal bacteriotherapy is reviewed here and possible mechanisms of action and potential applications explored. Published reports on fecal bacteriotherapy are few in number, and detail the results of small uncontrolled open studies and case reports. Nevertheless, given the promising clinical responses, formal research into fecal bacteriotherapy is now warranted. PMID:15220681

  16. Glossina spp. gut bacterial flora and their putative role in fly-hosted trypanosome development.

    PubMed

    Geiger, Anne; Fardeau, Marie-Laure; Njiokou, Flobert; Ollivier, Bernard

    2013-01-01

    Human African trypanosomiasis (HAT) is caused by trypanosomes transmitted to humans by the tsetse fly, in which they accomplish their development into their infective metacyclic form. The crucial step in parasite survival occurs when it invades the fly midgut. Insect digestive enzymes and immune defenses may be involved in the modulation of the fly's vector competence, together with bacteria that could be present in the fly's midgut. In fact, in addition to the three bacterial symbionts that have previously been characterized, tsetse flies may harbor additional bacterial inhabitants. This review focuses on the diversity of the bacterial flora in Glossina, with regards to the fly species and their geographical distribution. The rationale was (i) that these newly identified bacteria, associated with tsetse flies, may contribute to vector competence as was shown in other insects and (ii) that differences may exist according to fly species and geographic area. A more complete knowledge of the bacterial microbiota of the tsetse fly and the role these bacteria play in tsetse biology may lead to novel ways of investigation in view of developing alternative anti-vector strategies for fighting human--and possibly animal--trypanosomiasis.

  17. Glossina spp. gut bacterial flora and their putative role in fly-hosted trypanosome development

    PubMed Central

    Geiger, Anne; Fardeau, Marie-Laure; Njiokou, Flobert; Ollivier, Bernard

    2013-01-01

    Human African trypanosomiasis (HAT) is caused by trypanosomes transmitted to humans by the tsetse fly, in which they accomplish their development into their infective metacyclic form. The crucial step in parasite survival occurs when it invades the fly midgut. Insect digestive enzymes and immune defenses may be involved in the modulation of the fly's vector competence, together with bacteria that could be present in the fly's midgut. In fact, in addition to the three bacterial symbionts that have previously been characterized, tsetse flies may harbor additional bacterial inhabitants. This review focuses on the diversity of the bacterial flora in Glossina, with regards to the fly species and their geographical distribution. The rationale was (i) that these newly identified bacteria, associated with tsetse flies, may contribute to vector competence as was shown in other insects and (ii) that differences may exist according to fly species and geographic area. A more complete knowledge of the bacterial microbiota of the tsetse fly and the role these bacteria play in tsetse biology may lead to novel ways of investigation in view of developing alternative anti-vector strategies for fighting human—and possibly animal—trypanosomiasis. PMID:23898466

  18. Seasonal Variation in Human Gut Microbiome Composition

    PubMed Central

    Davenport, Emily R.; Mizrahi-Man, Orna; Michelini, Katelyn; Barreiro, Luis B.; Ober, Carole; Gilad, Yoav

    2014-01-01

    The composition of the human gut microbiome is influenced by many environmental factors. Diet is thought to be one of the most important determinants, though we have limited understanding of the extent to which dietary fluctuations alter variation in the gut microbiome between individuals. In this study, we examined variation in gut microbiome composition between winter and summer over the course of one year in 60 members of a founder population, the Hutterites. Because of their communal lifestyle, Hutterite diets are similar across individuals and remarkably stable throughout the year, with the exception that fresh produce is primarily served during the summer and autumn months. Our data indicate that despite overall gut microbiome stability within individuals over time, there are consistent and significant population-wide shifts in microbiome composition across seasons. We found seasonal differences in both (i) the abundance of particular taxa (false discovery rate <0.05), including highly abundant phyla Bacteroidetes and Firmicutes, and (ii) overall gut microbiome diversity (by Shannon diversity; P = 0.001). It is likely that the dietary fluctuations between seasons with respect to produce availability explain, at least in part, these differences in microbiome composition. For example, high levels of produce containing complex carbohydrates consumed during the summer months might explain increased abundance of Bacteroidetes, which contain complex carbohydrate digesters, and decreased levels of Actinobacteria, which have been negatively correlated to fiber content in food questionnaires. Our observations demonstrate the plastic nature of the human gut microbiome in response to variation in diet. PMID:24618913

  19. Gut Microbial Flora, Prebiotics, and Probiotics in IBD: Their Current Usage and Utility

    PubMed Central

    Scaldaferri, Franco; Gerardi, Viviana; Boškoski, Ivo; Bruno, Giovanni; Petito, Valentina; Laterza, Lucrezia; Cammarota, Giovanni; Gaetani, Eleonora; Sgambato, Alessandro; Gasbarrini, Antonio

    2013-01-01

    Inflammatory bowel diseases are chronic diseases affecting the gastrointestinal tract, whose major forms are represented by Crohn's disease (CD) and ulcerative colitis (UC). Their etiology is still unclear, although several factors have been identified as major determinants for induction or relapses. Among these, the role of the “forgotten organ”, gut microbiota, has become more appreciated in recent years. The delicate symbiotic relationship between the gut microbiota and the host appears to be lost in IBD. In this perspective, several studies have been conducted to assess the role of prebiotics and probiotics in gut microbiota modulation. This is a minireview aimed to address in an easy format (simple questions-simple answers) some common issues about the theme. An update on the role of selected constituents of gut microbiota in the pathogenesis of IBD is presented together with the analysis of the efficacy of gut microbiota modulation by prebiotics and probiotics administration in the management of IBD. PMID:23991417

  20. Insights from characterizing extinct human gut microbiomes.

    PubMed

    Tito, Raul Y; Knights, Dan; Metcalf, Jessica; Obregon-Tito, Alexandra J; Cleeland, Lauren; Najar, Fares; Roe, Bruce; Reinhard, Karl; Sobolik, Kristin; Belknap, Samuel; Foster, Morris; Spicer, Paul; Knight, Rob; Lewis, Cecil M

    2012-01-01

    In an effort to better understand the ancestral state of the human distal gut microbiome, we examine feces retrieved from archaeological contexts (coprolites). To accomplish this, we pyrosequenced the 16S rDNA V3 region from duplicate coprolite samples recovered from three archaeological sites, each representing a different depositional environment: Hinds Cave (~8000 years B.P.) in the southern United States, Caserones (1600 years B.P.) in northern Chile, and Rio Zape in northern Mexico (1400 years B.P.). Clustering algorithms grouped samples from the same site. Phyletic representation was more similar within sites than between them. A Bayesian approach to source-tracking was used to compare the coprolite data to published data from known sources that include, soil, compost, human gut from rural African children, human gut, oral and skin from US cosmopolitan adults and non-human primate gut. The data from the Hinds Cave samples largely represented unknown sources. The Caserones samples, retrieved directly from natural mummies, matched compost in high proportion. A substantial and robust proportion of Rio Zape data was predicted to match the gut microbiome found in traditional rural communities, with more minor matches to other sources. One of the Rio Zape samples had taxonomic representation consistent with a child. To provide an idealized scenario for sample preservation, we also applied source tracking to previously published data for Ötzi the Iceman and a soldier frozen for 93 years on a glacier. Overall these studies reveal that human microbiome data has been preserved in some coprolites, and these preserved human microbiomes match more closely to those from the rural communities than to those from cosmopolitan communities. These results suggest that the modern cosmopolitan lifestyle resulted in a dramatic change to the human gut microbiome.

  1. Insights from Characterizing Extinct Human Gut Microbiomes

    PubMed Central

    Tito, Raul Y.; Knights, Dan; Metcalf, Jessica; Obregon-Tito, Alexandra J.; Cleeland, Lauren; Najar, Fares; Roe, Bruce; Reinhard, Karl; Sobolik, Kristin; Belknap, Samuel; Foster, Morris; Spicer, Paul; Knight, Rob; Lewis, Cecil M.

    2012-01-01

    In an effort to better understand the ancestral state of the human distal gut microbiome, we examine feces retrieved from archaeological contexts (coprolites). To accomplish this, we pyrosequenced the 16S rDNA V3 region from duplicate coprolite samples recovered from three archaeological sites, each representing a different depositional environment: Hinds Cave (∼8000 years B.P.) in the southern United States, Caserones (1600 years B.P.) in northern Chile, and Rio Zape in northern Mexico (1400 years B.P.). Clustering algorithms grouped samples from the same site. Phyletic representation was more similar within sites than between them. A Bayesian approach to source-tracking was used to compare the coprolite data to published data from known sources that include, soil, compost, human gut from rural African children, human gut, oral and skin from US cosmopolitan adults and non-human primate gut. The data from the Hinds Cave samples largely represented unknown sources. The Caserones samples, retrieved directly from natural mummies, matched compost in high proportion. A substantial and robust proportion of Rio Zape data was predicted to match the gut microbiome found in traditional rural communities, with more minor matches to other sources. One of the Rio Zape samples had taxonomic representation consistent with a child. To provide an idealized scenario for sample preservation, we also applied source tracking to previously published data for Ötzi the Iceman and a soldier frozen for 93 years on a glacier. Overall these studies reveal that human microbiome data has been preserved in some coprolites, and these preserved human microbiomes match more closely to those from the rural communities than to those from cosmopolitan communities. These results suggest that the modern cosmopolitan lifestyle resulted in a dramatic change to the human gut microbiome. PMID:23251439

  2. Diet, the human gut microbiota, and IBD.

    PubMed

    Wu, Gary D; Bushmanc, Frederic D; Lewis, James D

    2013-12-01

    The human gut contains a vast number of microorganisms known collectively as the "gut microbiota". Despite its importance in maintaining the health of the host, growing evidence suggests the gut microbiota may also be an important factor in the pathogenesis of various diseases, a number of which have shown a rapid increase in incidence over the past few decades. Factors including age, genetics, and diet may influence microbiota composition. We used diet inventories and 16S rDNA sequencing to characterize fecal samples from 98 individuals. Fecal communities clustered into previously described enterotypes distinguished primarily by levels of Bacteroides and Prevotella. Enterotypes were associated with long-term diets, particularly protein and animal fat (Bacteroides) vs. simple carbohydrates (Prevotella). Although the distinction of enterotypes as either discrete clusters or a continuum will require additional investigation, numerous studies have demonstrated the co-exclusion of the closely related Prevotellaceae and Bacteroides genera in the gut microbiota of healthy human subjects where Prevotella appears to be a discriminatory taxon for residence in more agrarian societies. Ultimately, the impact of diet on the human gut microbiota may be an important environmental factor involved in the pathogenesis of disease states that show a rapidly increasing incidence in industrialized nations such as the inflammatory bowel diseases (IBD). PMID:23548695

  3. Human gut microbiome: the second genome of human body.

    PubMed

    Zhu, Baoli; Wang, Xin; Li, Lanjuan

    2010-08-01

    The human body is actually a super-organism that is composed of 10 times more microbial cells than our body cells. Metagenomic study of the human microbiome has demonstrated that there are 3.3 million unique genes in human gut, 150 times more genes than our own genome, and the bacterial diversity analysis showed that about 1000 bacterial species are living in our gut and a majority of them belongs to the divisions of Firmicutes and Bacteriodetes. In addition, most people share a core microbiota that comprises 50-100 bacterial species when the frequency of abundance at phylotype level is not considered, and a core microbiome harboring more than 6000 functional gene groups is present in the majority of human gut surveyed till now. Gut bacteria are not only critical for regulating gut metabolism, but also important for host immune system as revealed by animal studies.

  4. Alteration in Bacillus thuringiensis toxicity by curing gut flora: novel approach for mosquito resistance management.

    PubMed

    Patil, Chandrashekhar D; Borase, Hemant P; Salunke, Bipinchandra K; Patil, Satish V

    2013-09-01

    Mosquitoes are known for acquiring resistance against insecticides in many ways, namely target side mutation, enzyme modification, sequestration, quick elimination, etc. But, the role of microflora present in abundance in the larval midgut is less explored with respect to their role in insecticide resistance. During the course of their development, mosquitoes are continuously exposed to microbes and have naturally acquired midgut microbial flora. This midgut flora can modulate the mosquito's susceptibility to Bacillus thuringiensis (Bt) infection by degrading toxic Bt protein forms through an unknown mechanism. In this study, we show that microbe-free aseptic mosquito larvae displayed an increased susceptibility to Bt toxicity compared to larvae harboring natural microbial flora. Fourth instar larvae of Anopheles stephensi were treated separately with penicillin, streptomycin, erythromycin (100 μg/ml), and mixtures of all three antibiotics and then analyzed for Bt toxicity. We have also examined the influence of the mosquito's midgut microbial flora under microaerophilic condition on the Bt protein degradation through plate, broth, TLC, and UV-vis spectrophotometric assay. A better understanding of the roles of microbiota in preventing Bt toxicity to mosquitoes could potentially lead to the development of new sustainable mosquito control strategies.

  5. The human gut virome: a multifaceted majority

    PubMed Central

    Ogilvie, Lesley A.; Jones, Brian V.

    2015-01-01

    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 phages 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. PMID:26441861

  6. Peptidoglycan Recognition Proteins Protect Mice from Experimental Colitis by Promoting Normal Gut Flora and Preventing Induction of Interferon-γ

    PubMed Central

    Saha, Sukumar; Jing, Xuefang; Park, Shin Yong; Wang, Shiyong; Li, Xinna; Gupta, Dipika; Dziarski, Roman

    2010-01-01

    SUMMARY There are multiple mechanisms of maintaining tolerance in the gut that protect the intestine from excessive inflammatory response to intestinal microorganisms. We report here that all four mammalian Peptidoglycan Recognition Proteins (PGRPs or Pglyrps) protect the host from colitis induced by dextran sulfate sodium (DSS). Pglyrp1−/−, Pglyrp2−/−, Pglyrp3−/−, and Pglyrp4−/− mice are all more sensitive than wild type (WT) mice to DSS-induced colitis due to changes to more inflammatory gut microflora, higher production of interferon-γ and interferon-inducible genes, and increase in NK cells in the colon upon initial exposure to DSS, which leads to severe hyperplasia of the lamina propria, loss of epithelial cells, and ulceration in the colon. Thus in WT mice PGRPs protect the colon from early inflammatory response and loss of the barrier function of intestinal epithelium by promoting normal bacterial flora and by preventing damaging production of interferon-γ by NK cells in response to injury. PMID:20709292

  7. Rapid evolution of the human gut virome

    PubMed Central

    Minot, Samuel; Bryson, Alexandra; Chehoud, Christel; Wu, Gary D.; Lewis, James D.; Bushman, Frederic D.

    2013-01-01

    Humans are colonized by immense populations of viruses, which metagenomic analysis shows are mostly unique to each individual. To investigate the origin and evolution of the human gut virome, we analyzed the viral community of one adult individual over 2.5 y by extremely deep metagenomic sequencing (56 billion bases of purified viral sequence from 24 longitudinal fecal samples). After assembly, 478 well-determined contigs could be identified, which are inferred to correspond mostly to previously unstudied bacteriophage genomes. Fully 80% of these types persisted throughout the duration of the 2.5-y study, indicating long-term global stability. Mechanisms of base substitution, rates of accumulation, and the amount of variation varied among viral types. Temperate phages showed relatively lower mutation rates, consistent with replication by accurate bacterial DNA polymerases in the integrated prophage state. In contrast, Microviridae, which are lytic bacteriophages with single-stranded circular DNA genomes, showed high substitution rates (>10−5 per nucleotide each day), so that sequence divergence over the 2.5-y period studied approached values sufficient to distinguish new viral species. Longitudinal changes also were associated with diversity-generating retroelements and virus-encoded Clustered Regularly Interspaced Short Palindromic Repeats arrays. We infer that the extreme interpersonal diversity of human gut viruses derives from two sources, persistence of a small portion of the global virome within the gut of each individual and rapid evolution of some long-term virome members. PMID:23836644

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

    PubMed

    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.

  9. Human gut microbiota: repertoire and variations.

    PubMed

    Lagier, Jean-Christophe; Million, Matthieu; Hugon, Perrine; Armougom, Fabrice; Raoult, Didier

    2012-01-01

    The composition of human gut microbiota and their relationship with the host and, consequently, with human health and disease, presents several challenges to microbiologists. Originally dominated by culture-dependent methods for exploring this ecosystem, the advent of molecular tools has revolutionized our ability to investigate these relationships. However, many biases that have led to contradictory results have been identified. Microbial culturomics, a recent concept based on a use of several culture conditions with identification by MALDI-TOF followed by the genome sequencing of the new species cultured had allowed a complementarity with metagenomics. Culturomics allowed to isolate 31 new bacterial species, the largest human virus, the largest bacteria, and the largest Archaea from human. Moreover, some members of this ecosystem, such as Eukaryotes, giant viruses, Archaea, and Planctomycetes, have been neglected by the majority of studies. In addition, numerous factors, such as age, geographic provenance, dietary habits, antibiotics, or probiotics, can influence the composition of the microbiota. Finally, in addition to the countless biases associated with the study techniques, a considerable limitation to the interpretation of studies of human gut microbiota is associated with funding sources and transparency disclosures. In the future, studies independent of food industry funding and using complementary methods from a broad range of both culture-based and molecular tools will increase our knowledge of the repertoire of this complex ecosystem and host-microbiota mutualism.

  10. Human Gut Microbiota: Repertoire and Variations

    PubMed Central

    Lagier, Jean-Christophe; Million, Matthieu; Hugon, Perrine; Armougom, Fabrice; Raoult, Didier

    2012-01-01

    The composition of human gut microbiota and their relationship with the host and, consequently, with human health and disease, presents several challenges to microbiologists. Originally dominated by culture-dependent methods for exploring this ecosystem, the advent of molecular tools has revolutionized our ability to investigate these relationships. However, many biases that have led to contradictory results have been identified. Microbial culturomics, a recent concept based on a use of several culture conditions with identification by MALDI-TOF followed by the genome sequencing of the new species cultured had allowed a complementarity with metagenomics. Culturomics allowed to isolate 31 new bacterial species, the largest human virus, the largest bacteria, and the largest Archaea from human. Moreover, some members of this ecosystem, such as Eukaryotes, giant viruses, Archaea, and Planctomycetes, have been neglected by the majority of studies. In addition, numerous factors, such as age, geographic provenance, dietary habits, antibiotics, or probiotics, can influence the composition of the microbiota. Finally, in addition to the countless biases associated with the study techniques, a considerable limitation to the interpretation of studies of human gut microbiota is associated with funding sources and transparency disclosures. In the future, studies independent of food industry funding and using complementary methods from a broad range of both culture-based and molecular tools will increase our knowledge of the repertoire of this complex ecosystem and host-microbiota mutualism. PMID:23130351

  11. Human gut microbiota: does diet matter?

    PubMed

    Maukonen, Johanna; Saarela, Maria

    2015-02-01

    The human oro-gastrointestinal (GI) tract is a complex system, consisting of oral cavity, pharynx, oesophagus, stomach, small intestine, large intestine, rectum and anus, which all together with the accessory digestive organs constitute the digestive system. The function of the digestive system is to break down dietary constituents into small molecules and then absorb these for subsequent distribution throughout the body. Besides digestion and carbohydrate metabolism, the indigenous microbiota has an important influence on host physiological, nutritional and immunological processes, and commensal bacteria are able to modulate the expression of host genes that regulate diverse and fundamental physiological functions. The main external factors that can affect the composition of the microbial community in generally healthy adults include major dietary changes and antibiotic therapy. Changes in some selected bacterial groups have been observed due to controlled changes to the normal diet e.g. high-protein diet, high-fat diet, prebiotics, probiotics and polyphenols. More specifically, changes in the type and quantity of non-digestible carbohydrates in the human diet influence both the metabolic products formed in the lower regions of the GI tract and the bacterial populations detected in faeces. The interactions between dietary factors, gut microbiota and host metabolism are increasingly demonstrated to be important for maintaining homeostasis and health. Therefore the aim of this review is to summarise the effect of diet, and especially dietary interventions, on the human gut microbiota. Furthermore, the most important confounding factors (methodologies used and intrinsic human factors) in relation to gut microbiota analyses are elucidated. PMID:25156389

  12. The human gut microbiome, a taxonomic conundrum.

    PubMed

    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.

  13. Assessing the human gut microbiota in metabolic diseases.

    PubMed

    Karlsson, Fredrik; Tremaroli, Valentina; Nielsen, Jens; Bäckhed, Fredrik

    2013-10-01

    Recent findings have demonstrated that the gut microbiome complements our human genome with at least 100-fold more genes. In contrast to our Homo sapiens-derived genes, the microbiome is much more plastic, and its composition changes with age and diet, among other factors. An altered gut microbiota has been associated with several diseases, including obesity and diabetes, but the mechanisms involved remain elusive. Here we discuss factors that affect the gut microbiome, how the gut microbiome may contribute to metabolic diseases, and how to study the gut microbiome. Next-generation sequencing and development of software packages have led to the development of large-scale sequencing efforts to catalog the human microbiome. Furthermore, the use of genetically engineered gnotobiotic mouse models may increase our understanding of mechanisms by which the gut microbiome modulates host metabolism. A combination of classical microbiology, sequencing, and animal experiments may provide further insights into how the gut microbiota affect host metabolism and physiology.

  14. Assessing the Human Gut Microbiota in Metabolic Diseases

    PubMed Central

    Karlsson, Fredrik; Tremaroli, Valentina; Nielsen, Jens; Bäckhed, Fredrik

    2013-01-01

    Recent findings have demonstrated that the gut microbiome complements our human genome with at least 100-fold more genes. In contrast to our Homo sapiens–derived genes, the microbiome is much more plastic, and its composition changes with age and diet, among other factors. An altered gut microbiota has been associated with several diseases, including obesity and diabetes, but the mechanisms involved remain elusive. Here we discuss factors that affect the gut microbiome, how the gut microbiome may contribute to metabolic diseases, and how to study the gut microbiome. Next-generation sequencing and development of software packages have led to the development of large-scale sequencing efforts to catalog the human microbiome. Furthermore, the use of genetically engineered gnotobiotic mouse models may increase our understanding of mechanisms by which the gut microbiome modulates host metabolism. A combination of classical microbiology, sequencing, and animal experiments may provide further insights into how the gut microbiota affect host metabolism and physiology. PMID:24065795

  15. Impacts of Gut Bacteria on Human Health and Diseases

    PubMed Central

    Zhang, Yu-Jie; Li, Sha; Gan, Ren-You; Zhou, Tong; Xu, Dong-Ping; Li, Hua-Bin

    2015-01-01

    Gut bacteria are an important component of the microbiota ecosystem in the human gut, which is colonized by 1014 microbes, ten times more than the human cells. Gut bacteria play an important role in human health, such as supplying essential nutrients, synthesizing vitamin K, aiding in the digestion of cellulose, and promoting angiogenesis and enteric nerve function. However, they can also be potentially harmful due to the change of their composition when the gut ecosystem undergoes abnormal changes in the light of the use of antibiotics, illness, stress, aging, bad dietary habits, and lifestyle. Dysbiosis of the gut bacteria communities can cause many chronic diseases, such as inflammatory bowel disease, obesity, cancer, and autism. This review summarizes and discusses the roles and potential mechanisms of gut bacteria in human health and diseases. PMID:25849657

  16. Dietary modulation of the human gut microflora using prebiotics.

    PubMed

    Gibson, G R

    1998-10-01

    The human colonic flora has both beneficial and pathogenic potentials with respect to host health. There is now much interest in manipulation of the microbiota composition in order to improve the potentially beneficial aspects. The prebiotic approach dictates that non-viable food components are specifically fermented in the colon by indigenous bacteria thought to be of positive value, e.g. bifidobacteria, lactobacilli. Any food ingredient that enters the large intestine is a candidate prebiotic. However, to be effective, selectivity of the fermentation is essential. Most current attention and success has been derived using non-digestible oligosaccharides. Types primarily being looked at include those which contain fructose, xylose, soya, galactose, glucose and mannose. In particular, fructose-containing oligosaccharides, which occur naturally in a variety of plants such as onion, asparagus, chicory, banana and artichoke, fulfil the prebiotic criteria. Various data have shown that fructo-oligosaccharides (FOS) are specifically fermented by bifidobacteria. During controlled feeding studies, ingestion of these prebiotics causes bifidobacteria to become numerically dominant in faeces. Recent studies have indicated that a FOS dose of 4 g/d is prebiotic. To exploit this concept more fully, there is a need for assessments of (a) improved determination of the gut microbiota composition and activity; (b) the use of molecular methodologies to assess accurately prebiotic identities and develop efficient bacterial probing strategies; (c) the prebiotic potential of raw and processed foods; and (d) the health consequences of dietary modulation.

  17. Human gut microbiome viewed across age and geography

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  18. Phytoestrogen Metabolism by Adult Human Gut Microbiota.

    PubMed

    Gaya, Pilar; Medina, Margarita; Sánchez-Jiménez, Abel; Landete, José Mᵃ

    2016-08-09

    Phytoestrogens are plant-derived polyphenols with a structure similar to human estrogens. The three main groups of phytoestrogens, isoflavones, ellagitannins, and lignans, are transformed into equol, urolithins, and enterolignans, respectively, by bacteria. These metabolites have more estrogenic/antiestrogenic and antioxidant activities than their precursors, and they are more bioavailable. The aim of this study was to analyze the metabolism of isoflavones, lignans and ellagitannins by gut microbiota, and to study the possible correlation in the metabolism of these three groups of phytoestrogens. In vitro fermentation experiments were performed with feces samples from 14 healthy adult volunteers, and metabolite formation was measured by HPLC-PAD and HPLC-ESI/MS. Only the microbiota of one subject produced equol, while most of them showed production of O-desmethylangolensin (O-DMA). Significant inter-subject differences were observed in the metabolism of dihydrodaidzein and dihydrogenistein, while the glucoside isoflavones and their aglycones showed less variability, except for glycitin. Most subjects produced urolithins M-5 and E. Urolithin D was not detected, while uroltithin B was found in half of the individuals analyzed, and urolithins A and C were detected in two and four subjects, respectively. Enterolactone was found in all subjects, while enterodiol only appeared in five. Isoflavone metabolism could be correlated with the metabolism of lignans and ellagitannins. However, the metabolism of ellagitannins and lignans could not be correlated. This the first study where the metabolism of the three groups together of phytoestrogen, isoflavones, lignans, and ellagitannins by gut microbiota is analyzed.

  19. Potential applications of gut microbiota to control human physiology.

    PubMed

    Umu, Ozgün Candan Onarman; Oostindjer, Marije; Pope, Phillip B; Svihus, Birger; Egelandsdal, Bjørg; Nes, Ingolf F; Diep, Dzung B

    2013-11-01

    The microorganisms living in our gut have been a black box to us for a long time. However, with the recent advances in high throughput DNA sequencing technologies, it is now possible to assess virtually all microorganisms in our gut including non-culturable ones. With the use of powerful bioinformatics tools to deal with multivariate analyses of huge amounts of data from metagenomics, metatranscriptomics, metabolomics, we now start to gain some important insights into these tiny gut inhabitants. Our knowledge is increasing about who they are, to some extent, what they do and how they affect our health. Gut microbiota have a broad spectrum of possible effects on health, from preventing serious diseases, improving immune system and gut health to stimulating the brain centers responsible for appetite and food intake control. Further, we may be on the verge of being capable of manipulating the gut microbiota by diet control to possibly improve our health. Diets consisting of different components that are fermentable by microbiota are substrates for different kinds of microbes in the gut. Thus, diet control can be used to favor the growth of some selected gut inhabitants. Nowadays, the gut microbiota is taken into account as a separate organ in human body and their activities and metabolites in gut have many physiological and neurological effects. In this mini-review, we discuss the diversity of gut microbiota, the technologies used to assess them, factors that affect microbial composition and metabolites that affect human physiology, and their potential applications in satiety control via the gut-brain axis.

  20. Phytoestrogen Metabolism by Adult Human Gut Microbiota.

    PubMed

    Gaya, Pilar; Medina, Margarita; Sánchez-Jiménez, Abel; Landete, José Mᵃ

    2016-01-01

    Phytoestrogens are plant-derived polyphenols with a structure similar to human estrogens. The three main groups of phytoestrogens, isoflavones, ellagitannins, and lignans, are transformed into equol, urolithins, and enterolignans, respectively, by bacteria. These metabolites have more estrogenic/antiestrogenic and antioxidant activities than their precursors, and they are more bioavailable. The aim of this study was to analyze the metabolism of isoflavones, lignans and ellagitannins by gut microbiota, and to study the possible correlation in the metabolism of these three groups of phytoestrogens. In vitro fermentation experiments were performed with feces samples from 14 healthy adult volunteers, and metabolite formation was measured by HPLC-PAD and HPLC-ESI/MS. Only the microbiota of one subject produced equol, while most of them showed production of O-desmethylangolensin (O-DMA). Significant inter-subject differences were observed in the metabolism of dihydrodaidzein and dihydrogenistein, while the glucoside isoflavones and their aglycones showed less variability, except for glycitin. Most subjects produced urolithins M-5 and E. Urolithin D was not detected, while uroltithin B was found in half of the individuals analyzed, and urolithins A and C were detected in two and four subjects, respectively. Enterolactone was found in all subjects, while enterodiol only appeared in five. Isoflavone metabolism could be correlated with the metabolism of lignans and ellagitannins. However, the metabolism of ellagitannins and lignans could not be correlated. This the first study where the metabolism of the three groups together of phytoestrogen, isoflavones, lignans, and ellagitannins by gut microbiota is analyzed. PMID:27517891

  1. Gut Inflammation and Immunity: What Is the Role of the Human Gut Virome?

    PubMed Central

    Focà, Alfredo; Quirino, Angela; Marascio, Nadia; Zicca, Emilia; Pavia, Grazia

    2015-01-01

    The human virome comprises viruses that infect host cells, virus-derived elements in our chromosomes, and viruses that infect other organisms, including bacteriophages and plant viruses. The development of high-throughput sequencing techniques has shown that the human gut microbiome is a complex community in which the virome plays a crucial role into regulation of intestinal immunity and homeostasis. Nevertheless, the size of the human virome is still poorly understood. Indeed the enteric virome is in a continuous and dynamic equilibrium with other components of the gut microbiome and the gut immune system, an interaction that may influence the health and disease of the host. We review recent evidence on the viruses found in the gastrointestinal tract, discussing their interactions with the resident bacterial microbiota and the host immune system, in order to explore the potential impact of the virome on human health. PMID:25944980

  2. Survival of Human Dental Plaque Flora in Various Transport Media

    PubMed Central

    Syed, Salam A.; Loesche, Walter J.

    1972-01-01

    Dental plaque samples from (i) subjects with no apparent oral disease, (ii) mentally retarded subjects with periodontal disease, and (iii) subjects with active caries were collected in three transport media viz. a dithiothreitol poised balanced mineral salt solution designated as reduced transport fluid (RTF), VMG II, and modified Stuart medium (SBL). The samples were dispersed by sonic treatment, diluted in the respective medium in which they were collected, and cultured on MM10 sucrose agar. The efficiency of the transport media in the survival of dental plaque flora was determined by comparing the quantitative recovery (expressed as percentage of the initial viable count) from the specimens stored for various lengths of time. The data showed a great variation in the recovery of the oral bacterial flora from the plaque samples. VMG II and SBL served better than RTF as storage media for non-disease-associated dental plaque cultured under strict anaerobic conditions. Recoveries of bacteria from periodontal plaque specimens stored in RTF were higher than SBL and VMG II under identical conditions. The organisms present in the carious plaque samples appeared to survive much better in RTF and VMG II than in SBL as determined by conventional anaerobic culturing technique. However, VMG II showed a higher recovery of organisms from these specimens with an increase in the storage period, suggesting multiplication of the plaque flora. RTF did not allow the growth of oral bacterial flora under all experimental conditions. On the basis of the relative performance of these media it is suggested that RTF is a satisfactory medium for the transport of oral bacteria present in the samples. PMID:4628799

  3. The human gut microbiota and its interactive connections to diet.

    PubMed

    Milani, C; Ferrario, C; Turroni, F; Duranti, S; Mangifesta, M; van Sinderen, D; Ventura, M

    2016-10-01

    The microbiota of the gastrointestinal tract plays an important role in human health. In addition to their metabolic interactions with dietary constituents, gut bacteria may also be involved in more complex host interactions, such as modulation of the immune system. Furthermore, the composition of the gut microbiota may be important in reducing the risk of contracting particular gut infections. Changes in the microbiota during an individual's lifespan are accompanied by modifications in multiple health parameters, and such observations have prompted intense scientific efforts aiming to understand the complex interactions between the microbiota and its human host, as well as how this may be influenced by diet.

  4. Effects of human intestinal flora on mutagenicity of and DNA adduct formation from food and environmental mutagens.

    PubMed

    Hirayama, K; Baranczewski, P; Akerlund, J E; Midtvedt, T; Möller, L; Rafter, J

    2000-11-01

    Although the intestinal flora is believed to have a critical role in carcinogenesis, little is known about the role of the human intestinal flora on the effects of mutagens in vivo. The aim of the present study was to address a possible role of the human intestinal flora in carcinogenesis, by exploiting human-flora-associated (HFA) mice. The capacity of human faeces to activate or inactivate 2-amino-3-methyl-3H:-imidazo[4,5-f]quinoline (IQ) and 2-nitrofluorene was determined using the Ames assay. Human faecal suspensions that were active in this regard were then selected and orally inoculated into germfree NMRI mice to generate HFA mice. HFA, germfree, conventionalized and conventional mice were administered IQ, 2-amino-9H:-pyrido[2,3-b]indole (2-amino-alpha-carboline; AAC) and 2-nitrofluorene. The activity of human intestinal flora against mutagens could be transferred into the mice. In comparing germfree mice and mice harbouring an intestinal flora, the presence of a flora was essential for the activities of faeces against mutagens. After administration of IQ and 2-nitrofluorene, DNA adducts were observed in the mice with a flora, while adducts were extremely low or absent in germfree animals. DNA adducts after AAC treatment were higher in germfree mice in some tissues including colon than in mice with bacteria. Differences in DNA adduct formation were also observed between HFA mice and mice with mouse flora in many tissues. These results clearly indicate that the intestinal flora have an active role in DNA adduct formation and that the role is different for the different chemicals to which the animals are exposed. The results also demonstrate that the human intestinal flora have different effects from the mouse flora on DNA adduct formation as well as in vitro metabolic activities against mutagens. Studies using HFA mice could thus provide much-needed information on the role of the human intestinal flora on carcinogenesis in vivo. PMID:11062175

  5. Obesity changes the human gut mycobiome

    PubMed Central

    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

  6. Obesity changes the human gut mycobiome.

    PubMed

    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

    2015-10-12

    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.

  7. Detection of carboxylesterase and esterase activity in culturable gut bacterial flora isolated from diamondback moth, Plutella xylostella (Linnaeus), from India and its possible role in indoxacarb degradation.

    PubMed

    Ramya, Shanivarsanthe Leelesh; Venkatesan, Thiruvengadam; Srinivasa Murthy, Kottilingam; Jalali, Sushil Kumar; Verghese, Abraham

    2016-01-01

    Diamondback moth (DBM), Plutella xylostella (Linnaeus), is a notorious pest of brassica crops worldwide and is resistant to all groups of insecticides. The insect system harbors diverse groups of microbiota, which in turn helps in enzymatic degradation of xenobiotic-like insecticides. The present study aimed to determine the diversity of gut microflora in DBM, quantify esterase activity and elucidate their possible role in degradation of indoxacarb. We screened 11 geographic populations of DBM in India and analyzed them for bacterial diversity. The culturable gut bacterial flora underwent molecular characterization with 16S rRNA. We obtained 25 bacterial isolates from larvae (n=13) and adults (n=12) of DBM. In larval gut isolates, gammaproteobacteria was the most abundant (76%), followed by bacilli (15.4%). Molecular characterization placed adult gut bacterial strains into three major classes based on abundance: gammaproteobacteria (66%), bacilli (16.7%) and flavobacteria (16.7%). Esterase activity from 19 gut bacterial isolates ranged from 0.072 to 2.32μmol/min/mg protein. Esterase bands were observed in 15 bacterial strains and the banding pattern differed in Bacillus cereus - KC985225 and Pantoea agglomerans - KC985229. The bands were characterized as carboxylesterase with profenofos used as an inhibitor. Minimal media study showed that B. cereus degraded indoxacarb up to 20%, so it could use indoxacarb for metabolism and growth. Furthermore, esterase activity was greater with minimal media than control media: 1.87 versus 0.26μmol/min/mg protein. Apart from the insect esterases, bacterial carboxylesterase may aid in the degradation of insecticides in DBM. PMID:26991291

  8. Gene expression profiling gut microbiota in different races of humans

    PubMed Central

    Chen, Lei; Zhang, Yu-Hang; Huang, Tao; Cai, Yu-Dong

    2016-01-01

    The gut microbiome is shaped and modified by the polymorphisms of microorganisms in the intestinal tract. Its composition shows strong individual specificity and may play a crucial role in the human digestive system and metabolism. Several factors can affect the composition of the gut microbiome, such as eating habits, living environment, and antibiotic usage. Thus, various races are characterized by different gut microbiome characteristics. In this present study, we studied the gut microbiomes of three different races, including individuals of Asian, European and American races. The gut microbiome and the expression levels of gut microbiome genes were analyzed in these individuals. Advanced feature selection methods (minimum redundancy maximum relevance and incremental feature selection) and four machine-learning algorithms (random forest, nearest neighbor algorithm, sequential minimal optimization, Dagging) were employed to capture key differentially expressed genes. As a result, sequential minimal optimization was found to yield the best performance using the 454 genes, which could effectively distinguish the gut microbiomes of different races. Our analyses of extracted genes support the widely accepted hypotheses that eating habits, living environments and metabolic levels in different races can influence the characteristics of the gut microbiome. PMID:26975620

  9. Gene expression profiling gut microbiota in different races of humans

    NASA Astrophysics Data System (ADS)

    Chen, Lei; Zhang, Yu-Hang; Huang, Tao; Cai, Yu-Dong

    2016-03-01

    The gut microbiome is shaped and modified by the polymorphisms of microorganisms in the intestinal tract. Its composition shows strong individual specificity and may play a crucial role in the human digestive system and metabolism. Several factors can affect the composition of the gut microbiome, such as eating habits, living environment, and antibiotic usage. Thus, various races are characterized by different gut microbiome characteristics. In this present study, we studied the gut microbiomes of three different races, including individuals of Asian, European and American races. The gut microbiome and the expression levels of gut microbiome genes were analyzed in these individuals. Advanced feature selection methods (minimum redundancy maximum relevance and incremental feature selection) and four machine-learning algorithms (random forest, nearest neighbor algorithm, sequential minimal optimization, Dagging) were employed to capture key differentially expressed genes. As a result, sequential minimal optimization was found to yield the best performance using the 454 genes, which could effectively distinguish the gut microbiomes of different races. Our analyses of extracted genes support the widely accepted hypotheses that eating habits, living environments and metabolic levels in different races can influence the characteristics of the gut microbiome.

  10. How informative is the mouse for human gut microbiota research?

    PubMed Central

    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. PMID:25561744

  11. How informative is the mouse for human gut microbiota research?

    PubMed

    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.

  12. Impact of residual and therapeutic doses of ciprofloxacin in the human-flora-associated mice model.

    PubMed

    Perrin-Guyomard, Agnes; Poul, Jean-Michel; Corpet, Denis E; Sanders, Pascal; Fernández, A Haydée; Bartholomew, Mary

    2005-07-01

    A study was conducted to evaluate the effects of therapeutic and residual doses of ciprofloxacin on the human intestinal flora implanted into germ-free mice. Ciprofloxacin was administered daily via drinking water at concentrations to provide doses of 0, 0.125, 1.25, and 12.5mg/kg b.w. Changes in the intestinal flora composition, alteration in bacterial enzyme activities, fecal short chain fatty acid concentration and bacterial cellular fatty acid profiles, overgrowth of resistant bacteria, and disruption of the colonization barrier were the endpoints evaluated in the feces of human-flora-associated (HFA) mice. Ciprofloxacin at all tested doses decreased significantly the aerobic populations and particularly the population of Enterobacteriaceae. Selection of resistant Bacteroides fragilis group was noticed in HFA mice receiving 12.5mg/kg b.w. In mice challenged with a Salmonella strain, exogenous Salmonella persisted in the feces of all treated mice indicating that the flora responsible for the colonization barrier effect was disturbed by the antibiotic treatment. None of the studied metabolic parameters of the flora were affected by ciprofloxacin at any dose level. Under the experimental conditions of the study, the no-observed-effect level of ciprofloxacin was found to be less than 0.125 mg/kg b.w.

  13. Gut Health in the era of the human gut microbiota: from metaphor to biovalue.

    PubMed

    Baty, Vincent; Mougin, Bruno; Dekeuwer, Catherine; Carret, Gérard

    2014-11-01

    The human intestinal ecosystem, previously called the gut microflora is now known as the Human Gut Microbiota (HGM). Microbiome research has emphasized the potential role of this ecosystem in human homeostasis, offering unexpected opportunities in therapeutics, far beyond digestive diseases. It has also highlighted ethical, social and commercial concerns related to the gut microbiota. As diet factors are accepted to be the major regulator of the gut microbiota, the modulation of its composition, either by antibiotics or by food intake, should be regarded as a fascinating tool for improving the human health. Scientists, the food industry, consumers and policymakers alike are involved in this new field of nutrition. Defining how knowledge about the HGM is being translated into public perception has never been addressed before. This raises the question of metaphors associated with the HGM, and how they could be used to improve public understanding, and to influence individual decision-making on healthcare policy. This article suggests that a meeting of stakeholders from the social sciences, basic research and the food industry, taking an epistemological approach to the HGM, is needed to foster close, innovative partnerships that will help shape public perception and enable novel behavioural interventions that would benefit public health.

  14. Gut Health in the era of the human gut microbiota: from metaphor to biovalue.

    PubMed

    Baty, Vincent; Mougin, Bruno; Dekeuwer, Catherine; Carret, Gérard

    2014-11-01

    The human intestinal ecosystem, previously called the gut microflora is now known as the Human Gut Microbiota (HGM). Microbiome research has emphasized the potential role of this ecosystem in human homeostasis, offering unexpected opportunities in therapeutics, far beyond digestive diseases. It has also highlighted ethical, social and commercial concerns related to the gut microbiota. As diet factors are accepted to be the major regulator of the gut microbiota, the modulation of its composition, either by antibiotics or by food intake, should be regarded as a fascinating tool for improving the human health. Scientists, the food industry, consumers and policymakers alike are involved in this new field of nutrition. Defining how knowledge about the HGM is being translated into public perception has never been addressed before. This raises the question of metaphors associated with the HGM, and how they could be used to improve public understanding, and to influence individual decision-making on healthcare policy. This article suggests that a meeting of stakeholders from the social sciences, basic research and the food industry, taking an epistemological approach to the HGM, is needed to foster close, innovative partnerships that will help shape public perception and enable novel behavioural interventions that would benefit public health. PMID:24610296

  15. Part 1: The Human Gut Microbiome in Health and Disease

    PubMed Central

    Bull, Matthew J.; Plummer, Nigel T.

    2014-01-01

    The bacterial cells harbored within the human gastrointestinal tract (GIT) outnumber the host’s cells by a factor of 10 and the genes encoded by the bacteria resident within the GIT outnumber their host’s genes by more than 100 times. These human digestive-tract associated microbes are referred to as the gut microbiome. The human gut microbiome and its role in both health and disease has been the subject of extensive research, establishing its involvement in human metabolism, nutrition, physiology, and immune function. Imbalance of the normal gut microbiota have been linked with gastrointestinal conditions such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), and wider systemic manifestations of disease such as obesity, type 2 diabetes, and atopy. In the first part of this review, we evaluate our evolving knowledge of the development, complexity, and functionality of the healthy gut microbiota, and the ways in which the microbial community is perturbed in dysbiotic disease states; the second part of this review covers the role of interventions that have been shown to modulate and stabilize the gut microbiota and also to restore it to its healthy composition from the dysbiotic states seen in IBS, IBD, obesity, type 2 diabetes, and atopy. PMID:26770121

  16. Part 1: The Human Gut Microbiome in Health and Disease.

    PubMed

    Bull, Matthew J; Plummer, Nigel T

    2014-12-01

    The bacterial cells harbored within the human gastrointestinal tract (GIT) outnumber the host's cells by a factor of 10 and the genes encoded by the bacteria resident within the GIT outnumber their host's genes by more than 100 times. These human digestive-tract associated microbes are referred to as the gut microbiome. The human gut microbiome and its role in both health and disease has been the subject of extensive research, establishing its involvement in human metabolism, nutrition, physiology, and immune function. Imbalance of the normal gut microbiota have been linked with gastrointestinal conditions such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), and wider systemic manifestations of disease such as obesity, type 2 diabetes, and atopy. In the first part of this review, we evaluate our evolving knowledge of the development, complexity, and functionality of the healthy gut microbiota, and the ways in which the microbial community is perturbed in dysbiotic disease states; the second part of this review covers the role of interventions that have been shown to modulate and stabilize the gut microbiota and also to restore it to its healthy composition from the dysbiotic states seen in IBS, IBD, obesity, type 2 diabetes, and atopy. PMID:26770121

  17. Country-specific antibiotic use practices impact the human gut resistome.

    PubMed

    Forslund, Kristoffer; Sunagawa, Shinichi; Kultima, Jens Roat; Mende, Daniel R; Arumugam, Manimozhiyan; Typas, Athanasios; Bork, Peer

    2013-07-01

    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 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 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 in these statistics match the observed resistance potential differences. The results are robust over time as the antibiotic resistance determinants of individuals persist in the human gut flora for at least a year. PMID:23568836

  18. Country-specific antibiotic use practices impact the human gut resistome.

    PubMed

    Forslund, Kristoffer; Sunagawa, Shinichi; Kultima, Jens Roat; Mende, Daniel R; Arumugam, Manimozhiyan; Typas, Athanasios; Bork, Peer

    2013-07-01

    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 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 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 in these statistics match the observed resistance potential differences. The results are robust over time as the antibiotic resistance determinants of individuals persist in the human gut flora for at least a year.

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

    PubMed

    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. PMID:26808106

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

    PubMed

    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.

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

    PubMed

    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.

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

    PubMed

    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. PMID:22683238

  3. Shotgun metaproteomics of the human distal gut microbiota

    SciTech Connect

    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.

  4. Application of metagenomics in the human gut microbiome.

    PubMed

    Wang, Wei-Lin; Xu, Shao-Yan; Ren, Zhi-Gang; Tao, Liang; Jiang, Jian-Wen; Zheng, Shu-Sen

    2015-01-21

    There are more than 1000 microbial species living in the complex human intestine. The gut microbial community plays an important role in protecting the host against pathogenic microbes, modulating immunity, regulating metabolic processes, and is even regarded as an endocrine organ. However, traditional culture methods are very limited for identifying microbes. With the application of molecular biologic technology in the field of the intestinal microbiome, especially metagenomic sequencing of the next-generation sequencing technology, progress has been made in the study of the human intestinal microbiome. Metagenomics can be used to study intestinal microbiome diversity and dysbiosis, as well as its relationship to health and disease. Moreover, functional metagenomics can identify novel functional genes, microbial pathways, antibiotic resistance genes, functional dysbiosis of the intestinal microbiome, and determine interactions and co-evolution between microbiota and host, though there are still some limitations. Metatranscriptomics, metaproteomics and metabolomics represent enormous complements to the understanding of the human gut microbiome. This review aims to demonstrate that metagenomics can be a powerful tool in studying the human gut microbiome with encouraging prospects. The limitations of metagenomics to be overcome are also discussed. Metatranscriptomics, metaproteomics and metabolomics in relation to the study of the human gut microbiome are also briefly discussed.

  5. Shotgun Metaproteomics of the Human Distal Gut Microbiota

    SciTech Connect

    Verberkmoes, Nathan C; Erickson, Alison L; Shah, Manesh B; Godzik, A; Rosenquist, M; Halfvarsson, J; Lefsrud, Mark G; Apajalahti, J.; Hettich, Robert {Bob} L; Jansson, J

    2009-01-01

    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 what genes were 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 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.

  6. Application of metagenomics in the human gut microbiome

    PubMed Central

    Wang, Wei-Lin; Xu, Shao-Yan; Ren, Zhi-Gang; Tao, Liang; Jiang, Jian-Wen; Zheng, Shu-Sen

    2015-01-01

    There are more than 1000 microbial species living in the complex human intestine. The gut microbial community plays an important role in protecting the host against pathogenic microbes, modulating immunity, regulating metabolic processes, and is even regarded as an endocrine organ. However, traditional culture methods are very limited for identifying microbes. With the application of molecular biologic technology in the field of the intestinal microbiome, especially metagenomic sequencing of the next-generation sequencing technology, progress has been made in the study of the human intestinal microbiome. Metagenomics can be used to study intestinal microbiome diversity and dysbiosis, as well as its relationship to health and disease. Moreover, functional metagenomics can identify novel functional genes, microbial pathways, antibiotic resistance genes, functional dysbiosis of the intestinal microbiome, and determine interactions and co-evolution between microbiota and host, though there are still some limitations. Metatranscriptomics, metaproteomics and metabolomics represent enormous complements to the understanding of the human gut microbiome. This review aims to demonstrate that metagenomics can be a powerful tool in studying the human gut microbiome with encouraging prospects. The limitations of metagenomics to be overcome are also discussed. Metatranscriptomics, metaproteomics and metabolomics in relation to the study of the human gut microbiome are also briefly discussed. PMID:25624713

  7. From lifetime to evolution: timescales of human gut microbiota adaptation.

    PubMed

    Quercia, Sara; Candela, Marco; Giuliani, Cristina; Turroni, Silvia; Luiselli, Donata; Rampelli, Simone; Brigidi, Patrizia; Franceschi, Claudio; Bacalini, Maria Giulia; Garagnani, Paolo; Pirazzini, Chiara

    2014-01-01

    Human beings harbor gut microbial communities that are essential to preserve human health. Molded by the human genome, the gut microbiota (GM) is an adaptive component of the human superorganisms that allows host adaptation at different timescales, optimizing host physiology from daily life to lifespan scales and human evolutionary history. The GM continuously changes from birth up to the most extreme limits of human life, reconfiguring its metagenomic layout in response to daily variations in diet or specific host physiological and immunological needs at different ages. On the other hand, the microbiota plasticity was strategic to face changes in lifestyle and dietary habits along the course of the recent evolutionary history, that has driven the passage from Paleolithic hunter-gathering societies to Neolithic agricultural farmers to modern Westernized societies. PMID:25408692

  8. From lifetime to evolution: timescales of human gut microbiota adaptation

    PubMed Central

    Quercia, Sara; Candela, Marco; Giuliani, Cristina; Turroni, Silvia; Luiselli, Donata; Rampelli, Simone; Brigidi, Patrizia; Franceschi, Claudio; Bacalini, Maria Giulia; Garagnani, Paolo; Pirazzini, Chiara

    2014-01-01

    Human beings harbor gut microbial communities that are essential to preserve human health. Molded by the human genome, the gut microbiota (GM) is an adaptive component of the human superorganisms that allows host adaptation at different timescales, optimizing host physiology from daily life to lifespan scales and human evolutionary history. The GM continuously changes from birth up to the most extreme limits of human life, reconfiguring its metagenomic layout in response to daily variations in diet or specific host physiological and immunological needs at different ages. On the other hand, the microbiota plasticity was strategic to face changes in lifestyle and dietary habits along the course of the recent evolutionary history, that has driven the passage from Paleolithic hunter-gathering societies to Neolithic agricultural farmers to modern Westernized societies. PMID:25408692

  9. In vitro fermentation of fructooligosaccharides with human gut bacteria.

    PubMed

    Mao, Bingyong; Li, Dongyao; Zhao, Jianxin; Liu, Xiaoming; Gu, Zhennan; Chen, Yong Q; Zhang, Hao; Chen, Wei

    2015-03-01

    Fructooligosaccharides (FOS) are one of the most studied prebiotics, selectively stimulating the growth of health-promoting bacteria in the host. However, there is increasing evidence that commensal gut bacteria, such as Bacteroides fragilis, Clostridium butyricum, Enterobacter cloacae, and even the pathogenic Escherichia coli BEN2908, are also able to metabolize FOS in vitro, and in some cases, FOS displayed adverse effects. Therefore, it is necessary to identify FOS-metabolizing species that are present in the gut. Unlike previous studies focusing on individual strains, this study used the traditional culture method combined with an alignment search on the gut bacteria database established from the Human Microbiome Project (HMP). The alignment results showed that homologous proteins for FOS transporters and glycosidases were distributed in 237 of the 453 strains of gut bacteria. La506 msmK encoding the ATP-binding protein and Aec45 fosGH1 encoding glycoside hydrolase were most widely distributed, in 155 and 55 strains, respectively. Seven of eight strains with both transporters and glycosidases were proven to be capable of metabolizing FOS, while five strains without either transporters or glycosidases were not. Fifteen species isolated from human feces and 11 species from the alignment search were identified to be FOS-metabolizing, of which Cronobacter sakazakii, Marvinbryantia formatexigens, Ruminococcus gnavus, and Weissella paramesenteroides are reported here for the first time. Thus, alignment search combined with the culture method is an effective method for obtaining a global view of the FOS-metabolizing bacteria in the gut and will be helpful in further investigating the relationship between FOS and human gut bacteria.

  10. Gut Microbial Succession Follows Acute Secretory Diarrhea in Humans

    PubMed Central

    David, Lawrence A.; Weil, Ana; Ryan, Edward T.; Calderwood, Stephen B.; Harris, Jason B.; Chowdhury, Fahima; Begum, Yasmin; Qadri, Firdausi

    2015-01-01

    ABSTRACT Disability after childhood diarrhea is an important burden on global productivity. Recent studies suggest that gut bacterial communities influence how humans recover from infectious diarrhea, but we still lack extensive data and mechanistic hypotheses for how these bacterial communities respond to diarrheal disease and its treatment. Here, we report that after Vibrio cholerae infection, the human gut microbiota undergoes an orderly and reproducible succession that features transient reversals in relative levels of enteric Bacteroides and Prevotella. Elements of this succession may be a common feature in microbiota recovery from acute secretory diarrhea, as we observed similar successional dynamics after enterotoxigenic Escherichia coli (ETEC) infection. Our metagenomic analyses suggest that multiple mechanisms drive microbial succession after cholera, including bacterial dispersal properties, changing enteric oxygen and carbohydrate levels, and phage dynamics. Thus, gut microbiota recovery after cholera may be predictable at the level of community structure but is driven by a complex set of temporally varying ecological processes. Our findings suggest opportunities for diagnostics and therapies targeting the gut microbiota in humans recovering from infectious diarrhea. PMID:25991682

  11. Diet rapidly and reproducibly alters the human gut microbiome.

    PubMed

    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

    2014-01-23

    Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, 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 mammals, 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 disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.

  12. Diet rapidly and reproducibly alters the human gut microbiome.

    PubMed

    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

    2014-01-23

    Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, 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 mammals, 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 disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles. PMID:24336217

  13. Diet rapidly and reproducibly alters the human gut microbiome

    PubMed Central

    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

  14. Role of the normal gut microbiota

    PubMed Central

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

    2015-01-01

    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. PMID:26269668

  15. Role of the normal gut microbiota.

    PubMed

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

    2015-08-01

    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. PMID:26269668

  16. Role of the normal gut microbiota.

    PubMed

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

    2015-08-01

    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.

  17. The gut flora is required for the control of intestinal infection by poly(I:C) administration in neonates.

    PubMed

    Lacroix-Lamandé, Sonia; Guesdon, William; Drouet, Françoise; Potiron, Laurent; Lantier, Louis; Laurent, Fabrice

    2014-07-01

    We found that immunostimulation of the intestinal immune system of neonatal mice by poly(I:C) injection decreased intestinal infection by the parasite Cryptosporidium parvum. We showed that the presence of dendritic cells and the cooperation of mutually dependent cytokines, such as IL-12p40, and type I and type II IFNs, were involved in the mechanism of protection induced by poly(I:C). This protection is dependent not only on TLR3-TRIF signaling, but also on the activation of the TLR5-MyD88 pathway by gut microbiota. These results raise the possibility that flagellated intestinal commensal bacteria may, in the presence of natural or synthetic agonists of TLR3, provide synergy between the TRIF and MyD88 signaling pathways, thereby favoring the development of mucosal defenses. In this addendum, we summarize these recent findings and discuss their implications for neonatal infections and immunomodulatory strategies.

  18. The gut flora is required for the control of intestinal infection by poly(I:C) administration in neonates.

    PubMed

    Lacroix-Lamandé, Sonia; Guesdon, William; Drouet, Françoise; Potiron, Laurent; Lantier, Louis; Laurent, Fabrice

    2014-07-01

    We found that immunostimulation of the intestinal immune system of neonatal mice by poly(I:C) injection decreased intestinal infection by the parasite Cryptosporidium parvum. We showed that the presence of dendritic cells and the cooperation of mutually dependent cytokines, such as IL-12p40, and type I and type II IFNs, were involved in the mechanism of protection induced by poly(I:C). This protection is dependent not only on TLR3-TRIF signaling, but also on the activation of the TLR5-MyD88 pathway by gut microbiota. These results raise the possibility that flagellated intestinal commensal bacteria may, in the presence of natural or synthetic agonists of TLR3, provide synergy between the TRIF and MyD88 signaling pathways, thereby favoring the development of mucosal defenses. In this addendum, we summarize these recent findings and discuss their implications for neonatal infections and immunomodulatory strategies. PMID:24918602

  19. Dysbiotic events in gut microbiota: impact on human health.

    PubMed

    Schippa, Serena; Conte, Maria Pia

    2014-12-11

    The human body is colonized by a large number of microbes coexisting peacefully with their host. The most colonized site is the gastrointestinal tract (GIT). More than 70% of all the microbes in the human body are in the colon. The microorganism population is 10 times larger of the total number of our somatic and germ cells. Two bacterial phyla, accounting for more than 90% of the bacterial cells, dominate the healthy adult intestine: Firmicutes and Bacteroidetes. Considerable variability in the microbiota compositions between people is found when we look at the taxonomic level of species, and strains within species. It is possible to assert that the human microbiota could be compared to a fingerprint. The microbiota acts as a barrier from pathogens, exerts important metabolic functions, and regulates inflammatory response by stimulating the immune system. Gut microbial imbalance (dysbiosis), has been linked to important human diseases such as inflammation related disorders. The present review summarizes our knowledge on the gut microbiota in a healthy context, and examines intestinal dysbiosis in inflammatory bowel disease (IBD) patients; the most frequently reported disease proven to be associated with changes in the gut microbiota.

  20. Dysbiotic Events in Gut Microbiota: Impact on Human Health

    PubMed Central

    Schippa, Serena; Conte, Maria Pia

    2014-01-01

    The human body is colonized by a large number of microbes coexisting peacefully with their host. The most colonized site is the gastrointestinal tract (GIT). More than 70% of all the microbes in the human body are in the colon. The microorganism population is 10 times larger of the total number of our somatic and germ cells. Two bacterial phyla, accounting for more than 90% of the bacterial cells, dominate the healthy adult intestine: Firmicutes and Bacteroidetes. Considerable variability in the microbiota compositions between people is found when we look at the taxonomic level of species, and strains within species. It is possible to assert that the human microbiota could be compared to a fingerprint. The microbiota acts as a barrier from pathogens, exerts important metabolic functions, and regulates inflammatory response by stimulating the immune system. Gut microbial imbalance (dysbiosis), has been linked to important human diseases such as inflammation related disorders. The present review summarizes our knowledge on the gut microbiota in a healthy context, and examines intestinal dysbiosis in inflammatory bowel disease (IBD) patients; the most frequently reported disease proven to be associated with changes in the gut microbiota. PMID:25514560

  1. Microbial ecology: human gut microbes associated with obesity.

    PubMed

    Ley, Ruth E; Turnbaugh, Peter J; Klein, Samuel; Gordon, Jeffrey I

    2006-12-21

    Two groups of beneficial bacteria are dominant in the human gut, the Bacteroidetes and the Firmicutes. Here we show that the relative proportion of Bacteroidetes is decreased in obese people by comparison with lean people, and that this proportion increases with weight loss on two types of low-calorie diet. Our findings indicate that obesity has a microbial component, which might have potential therapeutic implications.

  2. Classification and quantification of bacteriophage taxa in human gut metagenomes

    PubMed Central

    Waller, Alison S; Yamada, Takuji; Kristensen, David M; Kultima, Jens Roat; Sunagawa, Shinichi; Koonin, Eugene V; Bork, Peer

    2014-01-01

    Bacteriophages have key roles in microbial communities, to a large extent shaping the taxonomic and functional composition of the microbiome, but data on the connections between phage diversity and the composition of communities are scarce. Using taxon-specific marker genes, we identified and monitored 20 viral taxa in 252 human gut metagenomic samples, mostly at the level of genera. On average, five phage taxa were identified in each sample, with up to three of these being highly abundant. The abundances of most phage taxa vary by up to four orders of magnitude between the samples, and several taxa that are highly abundant in some samples are absent in others. Significant correlations exist between the abundances of some phage taxa and human host metadata: for example, ‘Group 936 lactococcal phages' are more prevalent and abundant in Danish samples than in samples from Spain or the United States of America. Quantification of phages that exist as integrated prophages revealed that the abundance profiles of prophages are highly individual-specific and remain unique to an individual over a 1-year time period, and prediction of prophage lysis across the samples identified hundreds of prophages that are apparently active in the gut and vary across the samples, in terms of presence and lytic state. Finally, a prophage–host network of the human gut was established and includes numerous novel host–phage associations. PMID:24621522

  3. Gut Microbiota, Probiotics, and Human Health

    PubMed Central

    SUVOROV, Alexander

    2013-01-01

    The review is devoted to the problems of microbiota and the ways of it correction employing beneficial life bacteria- probiotics. It covers the issues related to the functioning of human microbiota and its importance for the health, individual variability of microbial content, functioning of the probiotics in the human organism and the history of probiotic studies with particular focus on the microbiological investigations in the USSR. The article discusses the safety issues related to probiotics and the problems with probiotic therapy, trying to explain the reasons for the side effects caused by probiotics. The necessity of personified selection of the probiotic strain or individual microbial therapy autoprobiotics is also discussed. PMID:24936366

  4. Natural mummification of the human gut preserves bacteriophage DNA.

    PubMed

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

    2016-01-01

    The natural mummification process of the human gut represents a unique opportunity to study the resulting microbial community structure and composition. While results are providing insights into the preservation of bacteria, fungi, pathogenic eukaryotes and eukaryotic viruses, no studies have demonstrated that the process of natural mummification also results in the preservation of bacteriophage DNA. We characterized the gut microbiome of three pre-Columbian Andean mummies, namely FI3, FI9 and FI12, and found sequences homologous to viruses. From the sequences attributable to viruses, 50.4% (mummy FI3), 1.0% (mummy FI9) and 84.4% (mummy FI12) were homologous to bacteriophages. Sequences corresponding to the Siphoviridae, Myoviridae, Podoviridae and Microviridae families were identified. Predicted putative bacterial hosts corresponded mainly to the Firmicutes and Proteobacteria, and included Bacillus, Staphylococcus, Clostridium, Escherichia, Vibrio, Klebsiella, Pseudomonas and Yersinia. Predicted functional categories associated with bacteriophages showed a representation of structural, replication, integration and entry and lysis genes. The present study suggests that the natural mummification of the human gut results in the preservation of bacteriophage DNA, representing an opportunity to elucidate the ancient phageome and to hypothesize possible mechanisms of preservation.

  5. Human gut microbes impact host serum metabolome and insulin sensitivity.

    PubMed

    Pedersen, Helle Krogh; Gudmundsdottir, Valborg; Nielsen, Henrik Bjørn; Hyotylainen, Tuulia; Nielsen, Trine; Jensen, Benjamin A H; Forslund, Kristoffer; Hildebrand, Falk; Prifti, Edi; Falony, Gwen; Le Chatelier, Emmanuelle; Levenez, Florence; Doré, Joel; Mattila, Ismo; Plichta, Damian R; Pöhö, Päivi; Hellgren, Lars I; Arumugam, Manimozhiyan; Sunagawa, Shinichi; Vieira-Silva, Sara; Jørgensen, Torben; Holm, Jacob Bak; Trošt, Kajetan; Kristiansen, Karsten; Brix, Susanne; Raes, Jeroen; Wang, Jun; Hansen, Torben; Bork, Peer; Brunak, Søren; Oresic, Matej; Ehrlich, S Dusko; Pedersen, Oluf

    2016-07-21

    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 are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders. PMID:27409811

  6. Human gut microbes impact host serum metabolome and insulin sensitivity.

    PubMed

    Pedersen, Helle Krogh; Gudmundsdottir, Valborg; Nielsen, Henrik Bjørn; Hyotylainen, Tuulia; Nielsen, Trine; Jensen, Benjamin A H; Forslund, Kristoffer; Hildebrand, Falk; Prifti, Edi; Falony, Gwen; Le Chatelier, Emmanuelle; Levenez, Florence; Doré, Joel; Mattila, Ismo; Plichta, Damian R; Pöhö, Päivi; Hellgren, Lars I; Arumugam, Manimozhiyan; Sunagawa, Shinichi; Vieira-Silva, Sara; Jørgensen, Torben; Holm, Jacob Bak; Trošt, Kajetan; Kristiansen, Karsten; Brix, Susanne; Raes, Jeroen; Wang, Jun; Hansen, Torben; Bork, Peer; Brunak, Søren; Oresic, Matej; Ehrlich, S Dusko; Pedersen, Oluf

    2016-07-21

    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 are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders.

  7. Phylogeny, culturing, and metagenomics of the human gut microbiota.

    PubMed

    Walker, Alan W; Duncan, Sylvia H; Louis, Petra; Flint, Harry J

    2014-05-01

    The human intestinal tract is colonised by a complex community of microbes, which can have major impacts on host health. Recent research on the gut microbiota has largely been driven by the advent of modern sequence-based techniques, such as metagenomics. Although these are powerful and valuable tools, they have limitations. Traditional culturing and phylogeny can mitigate some of these limitations, either by expanding reference databases or by assigning functionality to specific microbial lineages. As such, culture and phylogeny will continue to have crucially important roles in human microbiota research, and will be required for the development of novel therapeutics.

  8. Glucosinolate and Desulfo-glucosinolate Metabolism by a Selection of Human Gut Bacteria.

    PubMed

    Luang-In, Vijitra; Albaser, Abdulhadi Ali; Nueno-Palop, Carmen; Bennett, Mark H; Narbad, Arjan; Rossiter, John T

    2016-09-01

    Glucosinolate (GSL) hydrolysis is mediated by the enzyme myrosinase which together with specifier proteins can give rise to isothiocyanates (ITCs), thiocyanates, and nitriles (NITs) in cruciferous plants. However, little is known about the metabolism of GSLs by the human gut flora. The aim of the work was to investigate the metabolic fates of sinigrin (SNG), glucotropaeolin (GTP), gluconasturtiin (GNT), and their corresponding desulfo-GSLs (DS-GSLs). Three human gut bacterial strains, Enterococcus casseliflavus CP1, Lactobacillus agilis R16, and Escherichia coli VL8, were chosen for this study. GNT was metabolized to completion within 24 h to phenethyl ITC and phenethyl NIT (PNIT) by all bacteria, except for L. agilis R16 which produced only PNIT. At least 80 % of GTP and SNG were metabolized by all bacteria within 24 h to the corresponding ITCs and NITs. The pH of media over time gradually became acidic for both L. agilis R16 and E. coli VL8, while for E. casseliflavus CP1 the media became slightly alkaline with NIT and ITC production occurring between pH 3.0 and 7.5. ITC production peaked between 4 and 10 h in most cases and gradually declined while NIT production increased and remained relatively constant over time. The total percentage products accounted for 3-53 % of the initial GSL. NITs were produced from DS-GSLs suggesting an alternative metabolism via desulfation for the food based GSLs. The metal ion dependency for NIT production for GNT and its DS form was investigated where it was shown that Fe(2+) increased NIT production, while Mg(2+) stimulated the formation of ITC. PMID:27301252

  9. Evaluation of an Oral Subchronic Exposure of Deoxynivalenol on the Composition of Human Gut Microbiota in a Model of Human Microbiota-Associated Rats

    PubMed Central

    Saint-Cyr, Manuel J.; Perrin-Guyomard, Agnès; Houée, Paméla; Rolland, Jean-Guy; Laurentie, Michel

    2013-01-01

    Background Deoxynivalenol (DON), a mycotoxin produced by Fusarium species, is one of the most prevalent mycotoxins present in cereal crops worldwide. Due to its toxic properties, high stability and prevalence, the presence of DON in the food chain represents a health risk for both humans and animals. The gastrointestinal microbiota represents potentially the first target for these food contaminants. Thus, the effects of mycotoxins on the human gut microbiota is clearly an issue that needs to be addressed in further detail. Using a human microbiota-associated rat model, the aim of the present study was to evaluate the impact of a chronic exposure of DON on the composition of human gut microbiota. Methodology/Principal Findings Four groups of 5 germ free male rats each, housed in 4 sterile isolators, were inoculated with a different fresh human fecal flora. Rats were then fed daily by gavage with a solution of DON at 100 µg/kg bw for 4 weeks. Fecal samples were collected at day 0 before the beginning of the treatment; days 7, 16, 21, and 27 during the treatment; and 10 days after the end of the treatment at day 37. DON effect was assessed by real-time PCR quantification of dominant and subdominant bacterial groups in feces. Despite a different intestinal microbiota in each isolator, similar trends were generally observed. During oral DON exposure, a significant increase of 0.5 log10 was observed for the Bacteroides/Prevotella group during the first 3 weeks of administration. Concentration levels for Escherichia coli decreased at day 27. This significant decrease (0.9 log10 CFU/g) remained stable until the end of the experiment. Conclusions/Significance We have demonstrated an impact of oral DON exposure on the human gut microbiota composition. These findings can serve as a template for risk assessment studies of food contaminants on the human gut microbiota. PMID:24260424

  10. Human therapeutic and agricultural uses of antibacterial drugs and resistance of the enteric flora of humans.

    PubMed

    Siegel, D; Huber, W G; Drysdale, S

    1975-11-01

    Fecal samples were collected from five groups of people differing in the manner of their exposure to antibacterial drugs. The groups included: (i) people working on farms who were continuously in contact with the predominantly resistant florae of farm animals receiving rations containing antibacterial drugs, (ii) people residing on the same farms with no direct exposure to the farm animals, (iii) people treated with antibacterial drugs, (iv) untreated people residing with treated individuals, and (v) untreated people with no exposure to farm animals or treated individuals. The samples were examined by quantitative plating for proportions of antibiotic-resistant, gram-negative enteric organisms. Individual isolates were also examined for their susceptibility to 11 different antibacterial drugs. The results indicate that enteric florae unexposed directly to the selective effects of antibacterial drugs may be affected by contact with predominantly resistant florae directly exposed to antibacterial drugs.

  11. Human Therapeutic and Agricultural Uses of Antibacterial Drugs and Resistance of the Enteric Flora of Humans

    PubMed Central

    Siegel, D.; Huber, W. G.; Drysdale, S.

    1975-01-01

    Fecal samples were collected from five groups of people differing in the manner of their exposure to antibacterial drugs. The groups included: (i) people working on farms who were continuously in contact with the predominantly resistant florae of farm animals receiving rations containing antibacterial drugs, (ii) people residing on the same farms with no direct exposure to the farm animals, (iii) people treated with antibacterial drugs, (iv) untreated people residing with treated individuals, and (v) untreated people with no exposure to farm animals or treated individuals. The samples were examined by quantitative plating for proportions of antibiotic-resistant, gram-negative enteric organisms. Individual isolates were also examined for their susceptibility to 11 different antibacterial drugs. The results indicate that enteric florae unexposed directly to the selective effects of antibacterial drugs may be affected by contact with predominantly resistant florae directly exposed to antibacterial drugs. PMID:1108775

  12. Iron supplementation promotes gut microbiota metabolic activity but not colitis markers in human gut microbiota-associated rats.

    PubMed

    Dostal, Alexandra; Lacroix, Christophe; Pham, Van T; Zimmermann, Michael B; Del'homme, Christophe; Bernalier-Donadille, Annick; Chassard, Christophe

    2014-06-28

    The global prevalence of Fe deficiency is high and a common corrective strategy is oral Fe supplementation, which may affect the commensal gut microbiota and gastrointestinal health. The aim of the present study was to investigate the impact of different dietary Fe concentrations on the gut microbiota and gut health of rats inoculated with human faecal microbiota. Rats (8 weeks old, n 40) were divided into five (n 8 each) groups and fed diets differing only in Fe concentration during an Fe-depletion period (12 weeks) and an Fe-repletion period (4 weeks) as follows: (1) Fe-sufficient diet throughout the study period; (2) Fe-sufficient diet followed by 70 mg Fe/kg diet; (3) Fe-depleted diet throughout the study period; (4) Fe-depleted diet followed by 35 mg Fe/kg diet; (5) Fe-depleted diet followed by 70 mg Fe/kg diet. Faecal and caecal samples were analysed for gut microbiota composition (quantitative PCR and pyrosequencing) and bacterial metabolites (HPLC), and intestinal tissue samples were investigated histologically. Fe depletion did not significantly alter dominant populations of the gut microbiota and did not induce Fe-deficiency anaemia in the studied rats. Provision of the 35 mg Fe/kg diet after feeding an Fe-deficient diet significantly increased the abundance of dominant bacterial groups such as Bacteroides spp. and Clostridium cluster IV members compared with that of an Fe-deficient diet. Fe supplementation increased gut microbial butyrate concentration 6-fold compared with Fe depletion and did not affect histological colitis scores. The present results suggest that Fe supplementation enhances the concentration of beneficial gut microbiota metabolites and thus may contribute to gut health.

  13. The Human Neonatal Gut Microbiome: A Brief Review

    PubMed Central

    Gritz, Emily C.; Bhandari, Vineet

    2015-01-01

    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, has 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 (NEC) in preterm infants. We discuss the evidence supporting enteral pre- and pro-biotic supplementation of commensal organisms such as Bifidobacterium and Lactobacillus in the neonatal period, and their role in the prevention and amelioration of NEC in premature infants. Finally, we review directions to consider for further research to promote human health within this field. PMID:25798435

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

    PubMed

    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.

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

    PubMed

    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. PMID:27133729

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

    SciTech Connect

    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. 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.

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

    DOE PAGES

    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. 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 onmore » 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.« less

  18. Gut Bifidobacteria Populations in Human Health and Aging

    PubMed Central

    Arboleya, Silvia; Watkins, Claire; Stanton, Catherine; Ross, R. Paul

    2016-01-01

    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 childhood to old age. Bifidobacterium longum, B. breve, and B. bifidum are generally dominant in infants, whereas B. catenulatum, B. adolescentis and, as well as B. longum are more prevalent in adults. Increasingly, evidence is accumulating which shows beneficial effects 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 have been 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 compositional changes associated with different stages in life, highlighting their beneficial role, as well as their presence or absence in many disease states.

  19. Gut Bifidobacteria Populations in Human Health and Aging

    PubMed Central

    Arboleya, Silvia; Watkins, Claire; Stanton, Catherine; Ross, R. Paul

    2016-01-01

    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 childhood to old age. Bifidobacterium longum, B. breve, and B. bifidum are generally dominant in infants, whereas B. catenulatum, B. adolescentis and, as well as B. longum are more prevalent in adults. Increasingly, evidence is accumulating which shows beneficial effects 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 have been 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 compositional changes associated with different stages in life, highlighting their beneficial role, as well as their presence or absence in many disease states. PMID:27594848

  20. Human colon-derived soluble factors modulate gut microbiota composition.

    PubMed

    Hevia, Arancha; Bernardo, David; Montalvillo, Enrique; Al-Hassi, Hafid O; Fernández-Salazar, Luis; Garrote, Jose A; Milani, Christian; Ventura, Marco; Arranz, Eduardo; Knight, Stella C; Margolles, Abelardo; Sánchez, Borja

    2015-01-01

    The commensal microbiota modulates immunological and metabolic aspects of the intestinal mucosa contributing to development of human gut diseases including inflammatory bowel disease. The host/microbiota interaction often referred to as a crosstalk, mainly focuses on the effect of the microbiota on the host neglecting effects that the host could elicit on the commensals. Colonic microenvironments from three human healthy controls (obtained from the proximal and distal colon, both in resting conditions and after immune - IL-15- and microbiota - LPS-in vitro challenges) were used to condition a stable fecal population. Subsequent 16S rRNA gene-based analyses were performed to study the effect induced by the host on the microbiota composition and function. Non-supervised principal component analysis (PCA) showed that all microbiotas, which had been conditioned with colonic microenvironments clustered together in terms of relative microbial composition, suggesting that soluble factors were modulating a stable fecal population independently from the treatment or the origin. Our findings confirmed that the host intestinal microenvironment has the capacity to modulate the gut microbiota composition via yet unidentified soluble factors. These findings indicate that an appropriate understanding of the factors of the host mucosal microenvironment affecting microbiota composition and function could improve therapeutic manipulation of the microbiota composition. PMID:25918688

  1. Gut Bifidobacteria Populations in Human Health and Aging.

    PubMed

    Arboleya, Silvia; Watkins, Claire; Stanton, Catherine; Ross, R Paul

    2016-01-01

    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 childhood to old age. Bifidobacterium longum, B. breve, and B. bifidum are generally dominant in infants, whereas B. catenulatum, B. adolescentis and, as well as B. longum are more prevalent in adults. Increasingly, evidence is accumulating which shows beneficial effects 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 have been 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 compositional changes associated with different stages in life, highlighting their beneficial role, as well as their presence or absence in many disease states. PMID:27594848

  2. Human Colon-Derived Soluble Factors Modulate Gut Microbiota Composition

    PubMed Central

    Hevia, Arancha; Bernardo, David; Montalvillo, Enrique; Al-Hassi, Hafid O.; Fernández-Salazar, Luis; Garrote, Jose A.; Milani, Christian; Ventura, Marco; Arranz, Eduardo; Knight, Stella C.; Margolles, Abelardo; Sánchez, Borja

    2015-01-01

    The commensal microbiota modulates immunological and metabolic aspects of the intestinal mucosa contributing to development of human gut diseases including inflammatory bowel disease. The host/microbiota interaction often referred to as a crosstalk, mainly focuses on the effect of the microbiota on the host neglecting effects that the host could elicit on the commensals. Colonic microenvironments from three human healthy controls (obtained from the proximal and distal colon, both in resting conditions and after immune – IL-15- and microbiota – LPS-in vitro challenges) were used to condition a stable fecal population. Subsequent 16S rRNA gene-based analyses were performed to study the effect induced by the host on the microbiota composition and function. Non-supervised principal component analysis (PCA) showed that all microbiotas, which had been conditioned with colonic microenvironments clustered together in terms of relative microbial composition, suggesting that soluble factors were modulating a stable fecal population independently from the treatment or the origin. Our findings confirmed that the host intestinal microenvironment has the capacity to modulate the gut microbiota composition via yet unidentified soluble factors. These findings indicate that an appropriate understanding of the factors of the host mucosal microenvironment affecting microbiota composition and function could improve therapeutic manipulation of the microbiota composition. PMID:25918688

  3. Human colon-derived soluble factors modulate gut microbiota composition.

    PubMed

    Hevia, Arancha; Bernardo, David; Montalvillo, Enrique; Al-Hassi, Hafid O; Fernández-Salazar, Luis; Garrote, Jose A; Milani, Christian; Ventura, Marco; Arranz, Eduardo; Knight, Stella C; Margolles, Abelardo; Sánchez, Borja

    2015-01-01

    The commensal microbiota modulates immunological and metabolic aspects of the intestinal mucosa contributing to development of human gut diseases including inflammatory bowel disease. The host/microbiota interaction often referred to as a crosstalk, mainly focuses on the effect of the microbiota on the host neglecting effects that the host could elicit on the commensals. Colonic microenvironments from three human healthy controls (obtained from the proximal and distal colon, both in resting conditions and after immune - IL-15- and microbiota - LPS-in vitro challenges) were used to condition a stable fecal population. Subsequent 16S rRNA gene-based analyses were performed to study the effect induced by the host on the microbiota composition and function. Non-supervised principal component analysis (PCA) showed that all microbiotas, which had been conditioned with colonic microenvironments clustered together in terms of relative microbial composition, suggesting that soluble factors were modulating a stable fecal population independently from the treatment or the origin. Our findings confirmed that the host intestinal microenvironment has the capacity to modulate the gut microbiota composition via yet unidentified soluble factors. These findings indicate that an appropriate understanding of the factors of the host mucosal microenvironment affecting microbiota composition and function could improve therapeutic manipulation of the microbiota composition.

  4. Short-term effect of antibiotics on human gut microbiota.

    PubMed

    Panda, Suchita; El khader, Ismail; Casellas, Francesc; López Vivancos, Josefa; García Cors, Montserrat; Santiago, Alba; Cuenca, Silvia; Guarner, Francisco; Manichanh, Chaysavanh

    2014-01-01

    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.

  5. The gut microbiota in human energy homeostasis and obesity

    PubMed Central

    Knight, Rob; Leibel, Rudolph L.

    2016-01-01

    Numerous studies of rodents suggest that the gut micro-biota populations are sensitive to genetic and environmental influences, and can produce or influence afferent signals that directly or indirectly impinge on energy homeostatic systems affecting both energy balance (weight gain or loss) and energy stores. Fecal transplants from obese and lean human, and from mouse donors to gnotobiotic mice, result in adoption of the donor so-matotype by the formerly germ-free rodents. Thus, the microbiota is certainly implicated in the development of obesity, adiposity-related comorbidities, and the response to interventions designed to achieve sustained weight reduction in mice. More studies are needed to determine whether the microbiota plays a similarly potent role in human body-weight regulation and obesity. PMID:26257300

  6. The gut microbiota in human energy homeostasis and obesity.

    PubMed

    Rosenbaum, Michael; Knight, Rob; Leibel, Rudolph L

    2015-09-01

    Numerous studies of rodents suggest that the gut microbiota populations are sensitive to genetic and environmental influences, and can produce or influence afferent signals that directly or indirectly impinge on energy homeostatic systems affecting both energy balance (weight gain or loss) and energy stores. Fecal transplants from obese and lean human, and from mouse donors to gnotobiotic mice, result in adoption of the donor somatotype by the formerly germ-free rodents. Thus, the microbiota is certainly implicated in the development of obesity, adiposity-related comorbidities, and the response to interventions designed to achieve sustained weight reduction in mice. More studies are needed to determine whether the microbiota plays a similarly potent role in human body-weight regulation and obesity.

  7. Genome-Wide Association Studies of the Human Gut Microbiota.

    PubMed

    Davenport, Emily R; Cusanovich, Darren A; Michelini, Katelyn; Barreiro, Luis B; Ober, Carole; Gilad, Yoav

    2015-01-01

    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. PMID:26528553

  8. Genome-Wide Association Studies of the Human Gut Microbiota

    PubMed Central

    Davenport, Emily R.; Cusanovich, Darren A.; Michelini, Katelyn; Barreiro, Luis B.; Ober, Carole; Gilad, Yoav

    2015-01-01

    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. PMID:26528553

  9. Gut microbiota: next frontier in understanding human health and development of biotherapeutics

    PubMed Central

    Prakash, Satya; Rodes, Laetitia; Coussa-Charley, Michael; Tomaro-Duchesneau, Catherine

    2011-01-01

    The gut microbiota is a remarkable asset for human health. As a key element in the development and prevention of specific diseases, its study has yielded a new field of promising biotherapeutics. This review provides comprehensive and updated knowledge of the human gut microbiota, its implications in health and disease, and the potentials and limitations of its modification by currently available biotherapeutics to treat, prevent and/or restore human health, and future directions. Homeostasis of the gut microbiota maintains various functions which are vital to the maintenance of human health. Disruption of the intestinal ecosystem equilibrium (gut dysbiosis) is associated with a plethora of human diseases, including autoimmune and allergic diseases, colorectal cancer, metabolic diseases, and bacterial infections. Relevant underlying mechanisms by which specific intestinal bacteria populations might trigger the development of disease in susceptible hosts are being explored across the globe. Beneficial modulation of the gut microbiota using biotherapeutics, such as prebiotics, probiotics, and antibiotics, may favor health-promoting populations of bacteria and can be exploited in development of biotherapeutics. Other technologies, such as development of human gut models, bacterial screening, and delivery formulations eg, microencapsulated probiotics, may contribute significantly in the near future. Therefore, the human gut microbiota is a legitimate therapeutic target to treat and/or prevent various diseases. Development of a clear understanding of the technologies needed to exploit the gut microbiota is urgently required. PMID:21847343

  10. Aerobic bacterial oral flora of garter snakes: development of normal flora and pathogenic potential for snakes and humans.

    PubMed Central

    Goldstein, E J; Agyare, E O; Vagvolgyi, A E; Halpern, M

    1981-01-01

    Garter snakes that are used for scientific laboratory studies or kept as exotic pets often become ill and die early in captivity. They may also act as reservoirs of potential human pathogens or transmit infection to man. A total of 126 strains of aerobic and facultative bacteria, most potential human and snake pathogens, were isolated from 82 garter snake oropharyngeal cultures. Coagulase-negative Staphylococcus species were the most common species isolated. Acinetobacter calcoaceticus var. anitratus, Hafnia alvei, Arizona hinshawii, Salmonella species, Shigella species, Klebsiella oxytoca, and Pseudomonas aeruginosa were among the potential pathogens isolated. The spectrum of bacteria with potential for causing oral and pulmonary infections in garter snakes is greater than has been previously appreciated. Garter snakes should also be considered reservoirs of human pathogens, and appropriate precautions should be taken by laboratory personnel and pet owners. PMID:7240404

  11. The human gut microbiome impacts health and disease.

    PubMed

    Ehrlich, Stanislav Dusko

    2016-01-01

    The human gut microbiome can now be characterized in unprecedented detail by an approach based on high-throughput sequencing of total stool DNA, that we name quantitative metagenomics. Central to the approach is a catalog that lists all the genes of intestinal microbes that are known - 9.9 millions, identified by the analysis of 1267 stool samples. Beyond the gene list, genetic units that carry them begun to be known; many of these correspond to bacterial species that were never isolated and cultured yet. Quantitative metagenomics allows developing powerful algorithms to diagnose a disease, monitor patients and identify individuals at risk to progress towards a disease. This lays ground for developing new approaches to better restore and even preserve the health by modulation of the altered microbiome, which contributes to promote or aggravate a disease.

  12. Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment.

    PubMed

    Dobrijevic, Dragana; Abraham, Anne-Laure; Jamet, Alexandre; Maguin, Emmanuelle; van de Guchte, Maarten

    2016-01-01

    The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. The gut microbiota is shaped by millennia of evolution to co-exist with the host in commensal or symbiotic relationships. Members of the gut microbiota perform specific molecular functions important in the human gut environment. This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. We identified several functions that are overrepresented in the human gut bacteria which had not been recognized in a global approach. The observed under-representation of certain other functions may be equally important for gut homeostasis. Together, these analyses provide us with new information about this environment so critical to our health and well-being. PMID:27416027

  13. Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment

    PubMed Central

    Dobrijevic, Dragana; Abraham, Anne-Laure; Jamet, Alexandre; Maguin, Emmanuelle; van de Guchte, Maarten

    2016-01-01

    The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. The gut microbiota is shaped by millennia of evolution to co-exist with the host in commensal or symbiotic relationships. Members of the gut microbiota perform specific molecular functions important in the human gut environment. This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. We identified several functions that are overrepresented in the human gut bacteria which had not been recognized in a global approach. The observed under-representation of certain other functions may be equally important for gut homeostasis. Together, these analyses provide us with new information about this environment so critical to our health and well-being. PMID:27416027

  14. Functional Comparison of Bacteria from the Human Gut and Closely Related Non-Gut Bacteria Reveals the Importance of Conjugation and a Paucity of Motility and Chemotaxis Functions in the Gut Environment.

    PubMed

    Dobrijevic, Dragana; Abraham, Anne-Laure; Jamet, Alexandre; Maguin, Emmanuelle; van de Guchte, Maarten

    2016-01-01

    The human GI tract is a complex and still poorly understood environment, inhabited by one of the densest microbial communities on earth. The gut microbiota is shaped by millennia of evolution to co-exist with the host in commensal or symbiotic relationships. Members of the gut microbiota perform specific molecular functions important in the human gut environment. This can be illustrated by the presence of a highly expanded repertoire of proteins involved in carbohydrate metabolism, in phase with the large diversity of polysaccharides originating from the diet or from the host itself that can be encountered in this environment. In order to identify other bacterial functions that are important in the human gut environment, we investigated the distribution of functional groups of proteins in a group of human gut bacteria and their close non-gut relatives. Complementary to earlier global comparisons between different ecosystems, this approach should allow a closer focus on a group of functions directly related to the gut environment while avoiding functions related to taxonomically divergent microbiota composition, which may or may not be relevant for gut homeostasis. We identified several functions that are overrepresented in the human gut bacteria which had not been recognized in a global approach. The observed under-representation of certain other functions may be equally important for gut homeostasis. Together, these analyses provide us with new information about this environment so critical to our health and well-being.

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

    PubMed

    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. PMID:26957597

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

    PubMed

    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.

  17. Beneficial effects of human milk oligosaccharides on gut microbiota.

    PubMed

    Musilova, S; Rada, V; Vlkova, E; Bunesova, V

    2014-09-01

    Human milk is the gold standard for nourishment of early infants because it contains a number of bioactive components, such as human milk oligosaccharides (HMOs). The high concentration and structural diversity of HMOs are unique to humans. HMOs are a group of complex and diverse glycans that are resistant to gastrointestinal digestion and reach the infant colon as the first prebiotics. N-acetyl-glucosamine containing oligosaccharides were first identified 50 years ago as the 'bifidus factor', a selective growth substrate for intestinal bifidobacteria, thus providing a conceptual basis for HMO-specific bifidogenic activity. Bifidobacterial species are the main utilisers of HMOs in the gastrointestinal tract and represent the dominant microbiota of breast-fed infants, and they may play an important role in maintaining the general health of newborn children. Oligosaccharides are also known to directly interact with the surface of pathogenic bacteria, and various oligosaccharides in milk are believed to inhibit the binding of pathogens and toxins to host cell receptors. Furthermore, HMOs are thought to contribute to the development of infant intestine and brain. Oligosaccharides currently added to infant formula are structurally different from the oligosaccharides naturally occurring in human milk and, therefore, they are unlikely to mimic some of the structure-specific effects. In this review, we describe how HMOs can modulate gut microbiota. This article summarises information up to date about the relationship between the intestinal microbiota and HMOs, and other possible indirect effects of HMOs on intestinal environment.

  18. Quantitative Assessment of the Human Gut Microbiome using Multitag Pyrosequencing

    PubMed Central

    Sikaroodi, Masoumeh; Keshavarzian, Ali; Mutlu, Ece A.

    2013-01-01

    Recent advances in molecular technique have now made it possible to interrogate the human microbiome in depth to better understand the interactions with the host organism and its role in diseases. We now report the utility of using Length Heterogeneity Polymerase Chain Reaction (LH-PCR) to survey samples and a proprietary Multitagged Pyrosequencing (MTPS) methodology to interrogate the gut microbiome in healthy and disease states. We present an overview of our studies demonstrating that the application of these molecular biology techniques to an example disease state such as Inflammatory Bowel Disease (IBD). The findings show that there is a core mucosal bacterial microbiome (i.e. a mucosal biofilm) that is distinct from the luminal microbiome in health and that the mucosal microbiome appears to be dysbiotic in IBD. We propose that the mucosal microbiome forms a synergistic and stable interaction with the host immune system, while the lumen microbiome varies based on diet or other environmental factors. We define this composite ecosystem of the human microbiome and human host as the Human Metabiome. PMID:20491064

  19. Quantitative assessment of the human gut microbiome using multitag pyrosequencing.

    PubMed

    Gillevet, Patrick; Sikaroodi, Masoumeh; Keshavarzian, Ali; Mutlu, Ece A

    2010-05-01

    Recent advances in molecular techniques have now made it possible to interrogate the human microbiome in depth to better understand the interactions with the host organism and its role in diseases. We now report the utility of Length Heterogeneity Polymerase Chain Reaction (LH-PCR) to survey samples and a proprietary Multitagged Pyrosequencing (MTPS) methodology to interrogate the gut microbiome in healthy and disease states. We present an overview of our studies demonstrating the application of these molecular-biology techniques to an example disease state such as Inflammatory Bowel Disease (IBD). The findings show that there is a core mucosal bacterial microbiome (i.e., a mucosal biofilm) that is distinct from the luminal microbiome in health, and that the mucosal microbiome appears to be dysbiotic in IBD. We propose that the mucosal microbiome forms a synergistic and stable interaction with the host immune system, while the lumen microbiome varies based on diet or other environmental factors. We define this composite ecosystem of the human microbiome and human host as the Human Metabiome. PMID:20491064

  20. [Why could gut microbiota become a medication?].

    PubMed

    Bourlioux, P; Megerlin, F; Corthier, G; Gobert, J-G; Butel, M-J

    2014-09-01

    The gut microbiota (or gut flora) is a set of bacteria living in symbiosis with the host. Strictly associated with the intestinal tract and interacting with it, the gut microbiota is not a tissue nor an organ, but a supra-organism. A disruption of dialogue between bacteria and human cells is a risk factor or a possible cause of various diseases. The restoration of this dialogue, thanks to the transfer of the gut microbiota of a healthy individual to a patient whose balance of gut flora has been broken, is a new therapeutic approach. If its exact effect still eludes scientific understanding, its clinical benefit is well established for an indication, and is recently being tested for many others. The proven contribution of gut microbiota in the human physiological balance calls for intensifying research throughout the world about the state of knowledge and technologies, as well as on the legal and ethical dimension of fecal microbiota transfer. This didactic paper updates the questions in relation with this therapeutic act.

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

    PubMed

    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. PMID:26945826

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

    PubMed

    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.

  3. Confounding Effects of Metformin on the Human Gut Microbiome in Type 2 Diabetes.

    PubMed

    Mardinoglu, Adil; Boren, Jan; Smith, Ulf

    2016-01-12

    Type 2 diabetes (T2D) is associated with dysbiosis of the gut microbiota, though diabetes treatment regimens, including metformin, may confound the results. Forslund et al. (2015) identify distinct disease and drug signatures and highlight the importance of adjusting for treatment when investigating how T2D influences the human gut microbiome. PMID:26771114

  4. Confounding Effects of Metformin on the Human Gut Microbiome in Type 2 Diabetes.

    PubMed

    Mardinoglu, Adil; Boren, Jan; Smith, Ulf

    2016-01-12

    Type 2 diabetes (T2D) is associated with dysbiosis of the gut microbiota, though diabetes treatment regimens, including metformin, may confound the results. Forslund et al. (2015) identify distinct disease and drug signatures and highlight the importance of adjusting for treatment when investigating how T2D influences the human gut microbiome.

  5. Mucin glycan foraging in the human gut microbiome

    PubMed Central

    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

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

    PubMed Central

    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.

    2016-01-01

    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. PMID:26957597

  7. Efficiency of Various Growth Media in Recovering Oral Bacterial Flora from Human Dental Plaque

    PubMed Central

    Syed, Salam A.; Loesche, Walter J.

    1973-01-01

    MM10 sucrose blood agar (MM10 SB agar), N2C agar, Schaedler agar (SH agar), and mitis salivarius agar (MS agar) were tested for their ability to recover human dental plaque flora by a continuous anaerobic procedure and by a conventional anaerobic method. MM10 SB agar yielded higher recovery of bacteria from plaque samples as determined by the enumeration of colony-forming units (CFU). The CFU on N2C agar, SH agar, and MS agar were lower than MM10 SB agar when the continuous anaerobic procedure was used. The superior performance of MM10 SB agar was much more apparent when used for the cultivation of dental plaque by the conventional anaerobic method. Under these conditions the counts were consistently higher on MM10 SB agar as compared to the other media tested. However, the differential counts of Streptococcus sanguis and S. mutans from carious plaque samples were in general comparable on all culture media. Deletion of blood from MM10 SB agar did not lower counts. The elimination of dithiothreitol from this medium resulted in a significantly lower recovery of bacteria from the plaque samples when cultured by the conventional anaerobic method. The storage of MM10 SB agar for varying periods of time aerobic conditions did not seem to affect its performance. These findings suggest that MM10 SB agar is an ideal culture medium for the isolation, nonselective enumeration, and differential counts of bacteria present in normal and disease-associated plaques. PMID:4584588

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

    PubMed

    Forslund, Kristoffer; Hildebrand, Falk; Nielsen, Trine; Falony, Gwen; Le Chatelier, Emmanuelle; Sunagawa, Shinichi; Prifti, Edi; Vieira-Silva, Sara; Gudmundsdottir, Valborg; Krogh Pedersen, Helle; Arumugam, Manimozhiyan; Kristiansen, Karsten; Voigt, Anita Yvonne; Vestergaard, Henrik; Hercog, Rajna; Igor Costea, Paul; 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.

  9. Neonatal Gut Microbiota and Human Milk Glycans Cooperate to Attenuate Infection and Inflammation.

    PubMed

    Newburg, David S; He, Yingying

    2015-12-01

    Glycans of the intestinal mucosa and oligosaccharides of human milk influence the early colonization of the infant gut and establishment of mucosal homeostasis, and differences in colonization of the gut influence the ontogeny of glycans on the surface of the intestinal mucosa, proinflammatory signaling, homeostasis, and resilience to insult. This interkingdom reciprocal interaction is typical of a mutualistic symbiotic relationship. The period in which the infant gut most needs protection from hypersensitive inflammation overlaps with the recommended period of exclusive nursing; electively substituting artificial formula that lacks human milk protective glycans seems ill advised, especially for premature infants.

  10. Microbial community proteomics for characterizing the range of metabolic functions and activities of human gut microbiota

    DOE PAGES

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

    2015-01-01

    We found that the human gastrointestinal (GI) tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome component is not insignificant, but rather provides important functions that are absolutely critical to many aspects of human health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial community proteomics (sometimes referred to as metaproteomics) provides a powerful approach to measure the range and details of human gut microbiota functions and metabolic activities, revealing information about microbiome development and stability especially with regard to human health vs.more » disease states. In most cases, both microbial and human proteins are extracted from fecal samples and then measured by the high performance MS-based proteomics technology. We review the field of human gut microbiome community proteomics, with a focus on the experimental and informatics considerations involved in characterizing systems that range from low complexity defined model gut microbiota in gnotobiotic mice, to the simple gut microbiota in the GI tract of newborn infants, and finally to the complex gut microbiota in adults. Moreover, the current state-of-the-art in experimental and bioinformatics capabilities for community proteomics enable a detailed measurement of the gut microbiota, yielding valuable insights into the broad functional profiles of even complex microbiota. Future developments are likely to expand into improved analysis throughput and coverage depth, as well as post-translational modification characterizations.« less

  11. Microbial community proteomics for characterizing the range of metabolic functions and activities of human gut microbiota

    SciTech Connect

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

    2015-01-01

    We found that the human gastrointestinal (GI) tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome component is not insignificant, but rather provides important functions that are absolutely critical to many aspects of human health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial community proteomics (sometimes referred to as metaproteomics) provides a powerful approach to measure the range and details of human gut microbiota functions and metabolic activities, revealing information about microbiome development and stability especially with regard to human health vs. disease states. In most cases, both microbial and human proteins are extracted from fecal samples and then measured by the high performance MS-based proteomics technology. We review the field of human gut microbiome community proteomics, with a focus on the experimental and informatics considerations involved in characterizing systems that range from low complexity defined model gut microbiota in gnotobiotic mice, to the simple gut microbiota in the GI tract of newborn infants, and finally to the complex gut microbiota in adults. Moreover, the current state-of-the-art in experimental and bioinformatics capabilities for community proteomics enable a detailed measurement of the gut microbiota, yielding valuable insights into the broad functional profiles of even complex microbiota. Future developments are likely to expand into improved analysis throughput and coverage depth, as well as post-translational modification characterizations.

  12. Evolution of genetic diversity using networks: the human gut microbiome as a case study.

    PubMed

    Bapteste, E; Bicep, C; Lopez, P

    2012-07-01

    In order to study complex microbial communities and their associated mobile genetic elements, such as the human gut microbiome, evolutionists could explore their genetic diversity with shared sequence networks. In particular, the detection of remarkable structures in gene networks of the gut microbiome could serve to identify important functions within the community, and would ease comparison of data sets from microbiomes of various sources (human, ape, mouse etc.) in a single analysis.

  13. Impact of dietary polydextrose fiber on the human gut metabolome.

    PubMed

    Lamichhane, Santosh; Yde, Christian C; Forssten, Sofia; Ouwehand, Arthur C; Saarinen, Markku; Jensen, Henrik Max; Gibson, Glenn R; Rastall, Robert; Fava, Francesca; Bertram, Hanne Christine

    2014-10-01

    The aim of the present study was to elucidate the impact of polydextrose PDX an soluble fiber, on the human fecal metabolome by high-resolution nuclear magnetic resonance (NMR) spectroscopy-based metabolomics in a dietary intervention study (n = 12). Principal component analysis (PCA) revealed a strong effect of PDX consumption on the fecal metabolome, which could be mainly ascribed to the presence of undigested fiber and oligosaccharides formed from partial degradation of PDX. Our results demonstrate that NMR-based metabolomics is a useful technique for metabolite profiling of feces and for testing compliance to dietary fiber intake in such trials. In addition, novel associations between PDX and the levels of the fecal metabolites acetate and propionate could be identified. The establishment of a correlation between the fecal metabolome and levels of Bifidobacterium (R(2) = 0.66) and Bacteroides (R(2) = 0.46) demonstrates the potential of NMR-based metabolomics to elucidate metabolic activity of bacteria in the gut. PMID:25231382

  14. Human gut microbiota community structures in urban and rural populations in Russia

    PubMed Central

    Tyakht, Alexander V.; Kostryukova, Elena S.; Popenko, Anna S.; Belenikin, Maxim S.; Pavlenko, Alexander V.; Larin, Andrey K.; Karpova, Irina Y.; Selezneva, Oksana V.; Semashko, Tatyana A.; Ospanova, Elena A.; Babenko, Vladislav V.; Maev, Igor V.; Cheremushkin, Sergey V.; Kucheryavyy, Yuriy A.; Shcherbakov, Petr L.; Grinevich, Vladimir B.; Efimov, Oleg I.; Sas, Evgenii I.; Abdulkhakov, Rustam A.; Abdulkhakov, Sayar R.; Lyalyukova, Elena A.; Livzan, Maria A.; Vlassov, Valentin V.; Sagdeev, Renad Z.; Tsukanov, Vladislav V.; Osipenko, Marina F.; Kozlova, Irina V.; Tkachev, Alexander V.; Sergienko, Valery I.; Alexeev, Dmitry G.; Govorun, Vadim M.

    2013-01-01

    The microbial community of the human gut has a crucial role in sustaining host homeostasis. High-throughput DNA sequencing has delineated the structural and functional configurations of gut metagenomes in world populations. The microbiota of the Russian population is of particular interest to researchers, because Russia encompasses a uniquely wide range of environmental conditions and ethnogeographical cohorts. Here we conduct a shotgun metagenomic analysis of gut microbiota samples from 96 healthy Russian adult subjects, which reveals novel microbial community structures. The communities from several rural regions display similarities within each region and are dominated by the bacterial taxa associated with the healthy gut. Functional analysis shows that the metabolic pathways exhibiting differential abundance in the novel types are primarily associated with the trade-off between the Bacteroidetes and Firmicutes phyla. The specific signatures of the Russian gut microbiota are likely linked to the host diet, cultural habits and socioeconomic status. PMID:24036685

  15. Alterations of the human gut microbiome in multiple sclerosis.

    PubMed

    Jangi, Sushrut; Gandhi, Roopali; Cox, Laura M; Li, Ning; von Glehn, Felipe; Yan, Raymond; Patel, Bonny; Mazzola, Maria Antonietta; Liu, Shirong; Glanz, Bonnie L; Cook, Sandra; Tankou, Stephanie; Stuart, Fiona; Melo, Kirsy; Nejad, Parham; Smith, Kathleen; Topçuolu, Begüm D; Holden, James; Kivisäkk, Pia; Chitnis, Tanuja; De Jager, Philip L; Quintana, Francisco J; Gerber, Georg K; Bry, Lynn; Weiner, Howard L

    2016-01-01

    The gut microbiome plays an important role in immune function and has been implicated in several autoimmune disorders. Here we use 16S rRNA sequencing to investigate the gut microbiome in subjects with multiple sclerosis (MS, n=60) and healthy controls (n=43). Microbiome alterations in MS include increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signalling and NF-kB signalling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances of Prevotella and Sutterella, and decreased Sarcina, compared with untreated patients. MS patients of a second cohort show elevated breath methane compared with controls, consistent with our observation of increased gut Methanobrevibacter in MS in the first cohort. Further study is required to assess whether the observed alterations in the gut microbiome play a role in, or are a consequence of, MS pathogenesis. PMID:27352007

  16. Alterations of the human gut microbiome in multiple sclerosis

    PubMed Central

    Jangi, Sushrut; Gandhi, Roopali; Cox, Laura M.; Li, Ning; von Glehn, Felipe; Yan, Raymond; Patel, Bonny; Mazzola, Maria Antonietta; Liu, Shirong; Glanz, Bonnie L.; Cook, Sandra; Tankou, Stephanie; Stuart, Fiona; Melo, Kirsy; Nejad, Parham; Smith, Kathleen; Topçuolu, Begüm D.; Holden, James; Kivisäkk, Pia; Chitnis, Tanuja; De Jager, Philip L.; Quintana, Francisco J.; Gerber, Georg K.; Bry, Lynn; Weiner, Howard L.

    2016-01-01

    The gut microbiome plays an important role in immune function and has been implicated in several autoimmune disorders. Here we use 16S rRNA sequencing to investigate the gut microbiome in subjects with multiple sclerosis (MS, n=60) and healthy controls (n=43). Microbiome alterations in MS include increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signalling and NF-kB signalling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances of Prevotella and Sutterella, and decreased Sarcina, compared with untreated patients. MS patients of a second cohort show elevated breath methane compared with controls, consistent with our observation of increased gut Methanobrevibacter in MS in the first cohort. Further study is required to assess whether the observed alterations in the gut microbiome play a role in, or are a consequence of, MS pathogenesis. PMID:27352007

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

    PubMed

    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.

  18. Effects of an Antibacterial Soap on the Ecology of Aerobic Bacterial Flora of Human Skin

    PubMed Central

    Voss, J. G.

    1975-01-01

    The effects of ad lib use of an antibacterial soap containing 1.0% trichlorocarbanilide and 0.5% trifluoromethyldichlorocarbanilide on the bacterial flora of six skin sites of 132 subjects were measured by comparison with the flora of 93 control subjects who avoided the use of topical antibacterials. Each subject was examined once. The test soap produced significant reductions in geometric mean counts of the total aerobic flora on the back, chest, forearm, calf, and foot; counts were also reduced in the axilla, but not to a significant extent. The overall reduction by the test soap on all sites was 62% (P < 0.001). Neither age nor sex influenced the effect of the soap on the flora. The antibacterial soap also reduced the prevalence of Staphylococcus aureus on the skin, mostly by virtually eliminating it from areas other than the axilla. Partial inhibition of the gram-positive flora was not accompanied by an increase in gram-negative species. The latter were found principally in the axilla; Klebsiella pneumoniae and Enterobacter aerogenes were the species most frequently found. PMID:1103729

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

    PubMed Central

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

    2015-01-01

    The human gastrointestinal (GI) 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 mass spectrometry (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. PMID:25914197

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

    PubMed

    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.

  1. Elucidating the interactions between the human gut microbiota and its host through metabolic modeling

    PubMed Central

    Shoaie, Saeed; Nielsen, Jens

    2014-01-01

    Increased understanding of the interactions between the gut microbiota, diet and environmental effects may allow us to design efficient treatment strategies for addressing global health problems. Existence of symbiotic microorganisms in the human gut provides different functions for the host such as conversion of nutrients, training of the immune system, and resistance to pathogens. The gut microbiome also plays an influential role in maintaining human health, and it is a potential target for prevention and treatment of common disorders including obesity, type 2 diabetes, and atherosclerosis. Due to the extreme complexity of such disorders, it is necessary to develop mathematical models for deciphering the role of its individual elements as well as the entire system and such models may assist in better understanding of the interactions between the bacteria in the human gut and the host by use of genome-scale metabolic models (GEMs). Recently, GEMs have been employed to explore the interactions between predominant bacteria in the gut ecosystems. Additionally, these models enabled analysis of the contribution of each species to the overall metabolism of the microbiota through the integration of omics data. The outcome of these studies can be used for proposing optimal conditions for desired microbiome phenotypes. Here, we review the recent progress and challenges for elucidating the interactions between the human gut microbiota and host through metabolic modeling. We discuss how these models may provide scaffolds for analyzing high-throughput data, developing probiotics and prebiotics, evaluating the effects of probiotics and prebiotics and eventually designing clinical interventions. PMID:24795748

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

    PubMed Central

    Shashkova, Tatiana; Popenko, Anna; Tyakht, Alexander; Peskov, Kirill; Kosinsky, Yuri; Bogolubsky, Lev; Raigorodskii, Andrei; Ischenko, Dmitry; Alexeev, Dmitry; Govorun, Vadim

    2016-01-01

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

  3. Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life.

    PubMed

    Bäckhed, Fredrik; Roswall, Josefine; Peng, Yangqing; Feng, Qiang; Jia, Huijue; Kovatcheva-Datchary, Petia; Li, Yin; Xia, Yan; Xie, Hailiang; Zhong, Huanzi; Khan, Muhammad Tanweer; Zhang, Jianfeng; Li, Junhua; Xiao, Liang; Al-Aama, Jumana; Zhang, Dongya; Lee, Ying Shiuan; Kotowska, Dorota; Colding, Camilla; Tremaroli, Valentina; Yin, Ye; Bergman, Stefan; Xu, Xun; Madsen, Lise; Kristiansen, Karsten; Dahlgren, Jovanna; Wang, Jun; Jun, Wang

    2015-05-13

    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 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 composition and function, with cessation of breast-feeding, rather than introduction of solid food, being required for maturation into an adult-like microbiota. Microbiota composition and ecological network had distinctive features at each sampled stage, in accordance with functional maturation of the microbiome. Our findings establish a framework for understanding the interplay between the gut microbiome and the human body in early life. PMID:25974306

  4. Xenobiotics shape the physiology and gene expression of the active human gut microbiome

    PubMed Central

    Maurice, Corinne Ferrier; Haiser, Henry Joseph; Turnbaugh, Peter James

    2012-01-01

    SUMMARY The human gut contains trillions of microorganisms that influence our health by metabolizing xenobiotics, including host-targeted drugs and antibiotics. Recent efforts have characterized the diversity of this host-associated community, but it remains unclear which microorganisms are active and what perturbations influence this activity. Here, we combine flow cytometry, 16S rRNA gene sequencing, and metatranscriptomics to demonstrate that the gut contains a distinctive set of active microorganisms, primarily Firmicutes. Short-term exposure to a panel of xenobiotics significantly affected the physiology, structure, and gene expression of this active gut microbiome. Xenobiotic-responsive genes were found across multiple bacterial phyla, encoding antibiotic resistance, drug metabolism, and stress response pathways. These results demonstrate the power of moving beyond surveys of microbial diversity to better understand metabolic activity, highlight the unintended consequences of xenobiotics, and suggest that attempts at personalized medicine should consider inter-individual variations in the active human gut microbiome. PMID:23332745

  5. Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life.

    PubMed

    Bäckhed, Fredrik; Roswall, Josefine; Peng, Yangqing; Feng, Qiang; Jia, Huijue; Kovatcheva-Datchary, Petia; Li, Yin; Xia, Yan; Xie, Hailiang; Zhong, Huanzi; Khan, Muhammad Tanweer; Zhang, Jianfeng; Li, Junhua; Xiao, Liang; Al-Aama, Jumana; Zhang, Dongya; Lee, Ying Shiuan; Kotowska, Dorota; Colding, Camilla; Tremaroli, Valentina; Yin, Ye; Bergman, Stefan; Xu, Xun; Madsen, Lise; Kristiansen, Karsten; Dahlgren, Jovanna; Wang, Jun; Jun, Wang

    2015-05-13

    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 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 composition and function, with cessation of breast-feeding, rather than introduction of solid food, being required for maturation into an adult-like microbiota. Microbiota composition and ecological network had distinctive features at each sampled stage, in accordance with functional maturation of the microbiome. Our findings establish a framework for understanding the interplay between the gut microbiome and the human body in early life.

  6. Sex, Body Mass Index, and Dietary Fiber Intake Influence the Human Gut Microbiome

    PubMed Central

    Dominianni, Christine; Sinha, Rashmi; Goedert, James J.; Pei, Zhiheng; Yang, Liying; Hayes, Richard B.; Ahn, Jiyoung

    2015-01-01

    Increasing evidence suggests that the composition of the human gut microbiome is important in the etiology of human diseases; however, the personal factors that influence the gut microbiome composition are poorly characterized. Animal models point to sex hormone-related differentials in microbiome composition. In this study, we investigated the relationship of sex, body mass index (BMI) and dietary fiber intake with the gut microbiome in 82 humans. We sequenced fecal 16S rRNA genes by 454 FLX technology, then clustered and classified the reads to microbial genomes using the QIIME pipeline. Relationships of sex, BMI, and fiber intake with overall gut microbiome composition and specific taxon abundances were assessed by permutational MANOVA and multivariate logistic regression, respectively. We found that sex was associated with the gut microbiome composition overall (p=0.001). The gut microbiome in women was characterized by a lower abundance of Bacteroidetes (p=0.03). BMI (>25 kg/m2 vs. <25 kg/m2) was associated with the gut microbiome composition overall (p=0.05), and this relationship was strong in women (p=0.03) but not in men (p=0.29). Fiber from beans and from fruits and vegetables were associated, respectively, with greater abundance of Actinobacteria (p=0.006 and false discovery rate adjusted q=0.05) and Clostridia (p=0.009 and false discovery rate adjusted q=0.09). Our findings suggest that sex, BMI, and dietary fiber contribute to shaping the gut microbiome in humans. Better understanding of these relationships may have significant implications for gastrointestinal health and disease prevention. PMID:25874569

  7. Sex, body mass index, and dietary fiber intake influence the human gut microbiome.

    PubMed

    Dominianni, Christine; Sinha, Rashmi; Goedert, James J; Pei, Zhiheng; Yang, Liying; Hayes, Richard B; Ahn, Jiyoung

    2015-01-01

    Increasing evidence suggests that the composition of the human gut microbiome is important in the etiology of human diseases; however, the personal factors that influence the gut microbiome composition are poorly characterized. Animal models point to sex hormone-related differentials in microbiome composition. In this study, we investigated the relationship of sex, body mass index (BMI) and dietary fiber intake with the gut microbiome in 82 humans. We sequenced fecal 16S rRNA genes by 454 FLX technology, then clustered and classified the reads to microbial genomes using the QIIME pipeline. Relationships of sex, BMI, and fiber intake with overall gut microbiome composition and specific taxon abundances were assessed by permutational MANOVA and multivariate logistic regression, respectively. We found that sex was associated with the gut microbiome composition overall (p=0.001). The gut microbiome in women was characterized by a lower abundance of Bacteroidetes (p=0.03). BMI (>25 kg/m2 vs. <25 kg/m2) was associated with the gut microbiome composition overall (p=0.05), and this relationship was strong in women (p=0.03) but not in men (p=0.29). Fiber from beans and from fruits and vegetables were associated, respectively, with greater abundance of Actinobacteria (p=0.006 and false discovery rate adjusted q=0.05) and Clostridia (p=0.009 and false discovery rate adjusted q=0.09). Our findings suggest that sex, BMI, and dietary fiber contribute to shaping the gut microbiome in humans. Better understanding of these relationships may have significant implications for gastrointestinal health and disease prevention.

  8. Network-based Modeling of the Human Gut Microbiome

    PubMed Central

    Naqvi, Ammar; Rangwala, Huzefa; Keshavarzian, Ali

    2013-01-01

    In this paper we used a network-based approach to characterize the microflora abundance in colonic mucosal samples and correlate potential interactions between the identified species with respect to the healthy and diseased states. We analyzed the modelled network by computing several local and global network statistics, identified recurring patterns or motifs, fit the network models to a family of well-studied graph models. This study has demonstrated, for the first time, an approach that differentiated the gut microbiota in Alcoholic subjects and Healthy subjects using topological network analysis of the gut microbiome. PMID:20491063

  9. Network-based modeling of the human gut microbiome.

    PubMed

    Naqvi, Ammar; Rangwala, Huzefa; Keshavarzian, Ali; Gillevet, Patrick

    2010-05-01

    In this article, we used a network-based approach to characterize the microflora abundance in colonic mucosal samples and correlate potential interactions between the identified species with respect to the healthy and diseased states. We analyzed the modelled network by computing several local and global network statistics, identified recurring patterns or motifs, fit the network models to a family of well-studied graph models. This study has demonstrated, for the first time, an approach that differentiated the gut microbiota in alcoholic subjects and healthy subjects using topological network analysis of the gut microbiome. PMID:20491063

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

    PubMed

    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.

  11. The Gut Microbiota and Immune System Relationship in Human Graft-versus-Host Disease

    PubMed Central

    Laterza, Lucrezia; Rizzatti, Gianenrico; Gaetani, Eleonora; Chiusolo, Patrizia; Gasbarrini, Antonio

    2016-01-01

    Gut microbiota has gained increasing interest in the pathogenesis of immune-related diseases. In this context, graft-versus-host disease is a condition characterized by an immune response which frequently complicates and limits the outcomes of hematopoietic stem cell transplantations. Past studies, carried mostly in animals, already supported a relationship between gut microbiota and graft-versus-host disease. However, the possible mechanisms underlying this connection remain elusory. Moreover, strategies to prevent graft-versus-host disease are of great interest as well as the potential role of gut microbiota modulation. We reviewed the role of gut microbiota in the development of immune system and its involvement in the graft-versus-host disease, focusing on data available on humans. PMID:27158438

  12. Evaluation of genetic diversity among strains of the human gut commensal Bifidobacterium adolescentis

    PubMed Central

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

    2016-01-01

    Bifidobacteria are members of the human gut microbiota, being numerically dominant in the colon of infants, while also being prevalent in the large intestine of adults. In this study, we determined and analyzed the pan-genome of Bifidobacterium adolescentis, which is one of many bacteria found in the human adult gut microbiota. In silico analysis of the genome sequences of eighteen B. adolescentis strains isolated from various environments, such as human milk, human feces and bovine rumen, revealed a high level of genetic variability, resulting in an open pan-genome. Compared to other bifidobacterial taxa such as Bifidobacterium bifidum and Bifidobacterium breve, the more extensive B. adolescentis pan-genome supports the hypothesis that the genetic arsenal of this taxon expanded so as to become more adaptable to the variable and changing ecological niche of the gut. These increased genetic capabilities are particularly evident for genes required for dietary glycan-breakdown. PMID:27035119

  13. Evaluation of genetic diversity among strains of the human gut commensal Bifidobacterium adolescentis.

    PubMed

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

    2016-01-01

    Bifidobacteria are members of the human gut microbiota, being numerically dominant in the colon of infants, while also being prevalent in the large intestine of adults. In this study, we determined and analyzed the pan-genome of Bifidobacterium adolescentis, which is one of many bacteria found in the human adult gut microbiota. In silico analysis of the genome sequences of eighteen B. adolescentis strains isolated from various environments, such as human milk, human feces and bovine rumen, revealed a high level of genetic variability, resulting in an open pan-genome. Compared to other bifidobacterial taxa such as Bifidobacterium bifidum and Bifidobacterium breve, the more extensive B. adolescentis pan-genome supports the hypothesis that the genetic arsenal of this taxon expanded so as to become more adaptable to the variable and changing ecological niche of the gut. These increased genetic capabilities are particularly evident for genes required for dietary glycan-breakdown. PMID:27035119

  14. Evaluation of genetic diversity among strains of the human gut commensal Bifidobacterium adolescentis.

    PubMed

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

    2016-04-01

    Bifidobacteria are members of the human gut microbiota, being numerically dominant in the colon of infants, while also being prevalent in the large intestine of adults. In this study, we determined and analyzed the pan-genome of Bifidobacterium adolescentis, which is one of many bacteria found in the human adult gut microbiota. In silico analysis of the genome sequences of eighteen B. adolescentis strains isolated from various environments, such as human milk, human feces and bovine rumen, revealed a high level of genetic variability, resulting in an open pan-genome. Compared to other bifidobacterial taxa such as Bifidobacterium bifidum and Bifidobacterium breve, the more extensive B. adolescentis pan-genome supports the hypothesis that the genetic arsenal of this taxon expanded so as to become more adaptable to the variable and changing ecological niche of the gut. These increased genetic capabilities are particularly evident for genes required for dietary glycan-breakdown.

  15. Prebiotics, faecal transplants and microbial network units to stimulate biodiversity of the human gut microbiome.

    PubMed

    Van den Abbeele, Pieter; Verstraete, Willy; El Aidy, Sahar; Geirnaert, Annelies; Van de Wiele, Tom

    2013-07-01

    Accumulating evidence demonstrates the intimate association between human hosts and the gut microbiome. Starting at birth, the sterile gut of the newborn acquires a diverse spectrum of microbes, needed for immunological priming. However, current practices (caesarean sections, use of formula milk) deprive newborns from being exposed to this broad spectrum of microbes. Unnecessary use of antibiotics and excessive hygienic precautions (e.g. natural versus chlorinated drinking water) together with the Western diet further contribute to a decreased microbial diversity in the adult gut. This has been correlated with recurrent Clostridium difficile infection, inflammatory bowel diseases and obesity, among others. A healthy gut microbiome is thus characterized by a diverse network of metabolically interacting microbial members. In this context, we review several existing and novel approaches to manage the gut microbiome. First, prebiotic compounds should be re-defined in the sense that they should enhance the ecological biodiversity rather than stimulating single species. Recent studies highlight that structurally different polysaccharides require specific primary degraders but also enhance a similar network of secondary degraders that benefit from cross-feeding. A faecal transplantation is a second approach to restore biodiversity when the microbiota is severely dysbiosed, with promising results regarding C. difficile-associated disease and obesity-related metabolic syndromes. A final strategy is the introduction of key microbial network units, i.e. pre-organized microbial associations, which strengthen the overall microbial network of the gut microbiome that supports human health.

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

    PubMed

    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. PMID:27559027

  17. Strain-level dissection of the contribution of the gut microbiome to human metabolic disease.

    PubMed

    Zhang, Chenhong; Zhao, Liping

    2016-04-20

    The gut microbiota has been linked with metabolic diseases in humans, but demonstration of causality remains a challenge. The gut microbiota, as a complex microbial ecosystem, consists of hundreds of individual bacterial species, each of which contains many strains with high genetic diversity. Recent advances in genomic and metabolomic technologies are facilitating strain-level dissection of the contribution of the gut microbiome to metabolic diseases. Interventional studies and correlation analysis between variations in the microbiome and metabolome, captured by longitudinal sampling, can lead to the identification of specific bacterial strains that may contribute to human metabolic diseases via the production of bioactive metabolites. For example, high-quality draft genomes of prevalent gut bacterial strains can be assembled directly from metagenomic datasets using a canopy-based algorithm. Specific metabolites associated with a disease phenotype can be identified by nuclear magnetic resonance-based metabolomics of urine and other samples. Such multi-omics approaches can be employed to identify specific gut bacterial genomes that are not only correlated with detected metabolites but also encode the genes required for producing the precursors of those metabolites in the gut. Here, we argue that if a causative role can be demonstrated in follow-up mechanistic studies--for example, using gnotobiotic models--such functional strains have the potential to become biomarkers for diagnostics and targets for therapeutics.

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

    PubMed

    Li, Junhua; Jia, Huijue; Cai, Xianghang; Zhong, Huanzi; Feng, Qiang; Sunagawa, Shinichi; Arumugam, Manimozhiyan; Kultima, Jens Roat; Prifti, Edi; Nielsen, Trine; Juncker, Agnieszka Sierakowska; Manichanh, Chaysavanh; Chen, Bing; Zhang, Wenwei; Levenez, Florence; Wang, Juan; Xu, Xun; Xiao, Liang; Liang, Suisha; Zhang, Dongya; Zhang, Zhaoxi; Chen, Weineng; Zhao, Hailong; Al-Aama, Jumana Yousuf; Edris, Sherif; Yang, Huanming; Wang, Jian; Hansen, Torben; Nielsen, Henrik Bjørn; Brunak, Søren; Kristiansen, Karsten; Guarner, Francisco; Pedersen, Oluf; Doré, Joel; Ehrlich, S Dusko; Bork, Peer; Wang, Jun

    2014-08-01

    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 sequenced samples of the Metagenomics of the Human Intestinal Tract (MetaHit) project with 1,018 previously sequenced samples to create a cohort from three continents that is at least threefold larger than cohorts used for previous gene catalogs. From this we established the integrated gene catalog (IGC) 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 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. PMID:24997786

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

    PubMed

    Li, Junhua; Jia, Huijue; Cai, Xianghang; Zhong, Huanzi; Feng, Qiang; Sunagawa, Shinichi; Arumugam, Manimozhiyan; Kultima, Jens Roat; Prifti, Edi; Nielsen, Trine; Juncker, Agnieszka Sierakowska; Manichanh, Chaysavanh; Chen, Bing; Zhang, Wenwei; Levenez, Florence; Wang, Juan; Xu, Xun; Xiao, Liang; Liang, Suisha; Zhang, Dongya; Zhang, Zhaoxi; Chen, Weineng; Zhao, Hailong; Al-Aama, Jumana Yousuf; Edris, Sherif; Yang, Huanming; Wang, Jian; Hansen, Torben; Nielsen, Henrik Bjørn; Brunak, Søren; Kristiansen, Karsten; Guarner, Francisco; Pedersen, Oluf; Doré, Joel; Ehrlich, S Dusko; Bork, Peer; Wang, Jun

    2014-08-01

    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 sequenced samples of the Metagenomics of the Human Intestinal Tract (MetaHit) project with 1,018 previously sequenced samples to create a cohort from three continents that is at least threefold larger than cohorts used for previous gene catalogs. From this we established the integrated gene catalog (IGC) 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 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.

  20. Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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-...

  1. The Fiber Gap and the Disappearing Gut Microbiome: Implications for Human Nutrition.

    PubMed

    Deehan, Edward C; Walter, Jens

    2016-05-01

    Increasing evidence indicates that modern lifestyle, and specifically a Western diet, has led to a substantial depletion of the human gut microbiome. This loss is implicated in the rampant increase of chronic diseases, providing an incentive to fundamentally transform human nutrition towards being more holistic and microbiome-focused. PMID:27079516

  2. Genetic determinants of in vivo fitness and diet responsiveness in multiple human gut Bacteroides.

    PubMed

    Wu, Meng; McNulty, Nathan P; Rodionov, Dmitry A; Khoroshkin, Matvei S; Griffin, Nicholas W; Cheng, Jiye; Latreille, Phil; Kerstetter, Randall A; Terrapon, Nicolas; Henrissat, Bernard; Osterman, Andrei L; Gordon, Jeffrey I

    2015-10-01

    Libraries of tens of thousands of transposon mutants generated from each of four human gut Bacteroides strains, two representing the same species, were introduced simultaneously into gnotobiotic mice together with 11 other wild-type strains to generate a 15-member artificial human gut microbiota. Mice received one of two distinct diets monotonously, or both in different ordered sequences. Quantifying the abundance of mutants in different diet contexts allowed gene-level characterization of fitness determinants, niche, stability, and resilience and yielded a prebiotic (arabinoxylan) that allowed targeted manipulation of the community. The approach described is generalizable and should be useful for defining mechanisms critical for sustaining and/or approaches for deliberately reconfiguring the highly adaptive and durable relationship between the human gut microbiota and host in ways that promote wellness. PMID:26430127

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

    PubMed

    Shoaie, Saeed; Ghaffari, Pouyan; Kovatcheva-Datchary, Petia; Mardinoglu, Adil; Sen, Partho; Pujos-Guillot, Estelle; de Wouters, Tomas; Juste, Catherine; Rizkalla, Salwa; Chilloux, Julien; Hoyles, Lesley; Nicholson, Jeremy K; Dore, Joel; Dumas, Marc E; Clement, Karine; Bäckhed, Fredrik; Nielsen, Jens

    2015-08-01

    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-microbe and microbe-host interactions. Here, we describe the CASINO (Community And Systems-level INteractive Optimization) toolbox, a comprehensive computational platform for analysis of microbial communities through metabolic modeling. We first validated the toolbox by simulating and testing the performance 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. PMID:26244934

  4. Genetic determinants of in vivo fitness and diet responsiveness in multiple human gut Bacteroides

    PubMed Central

    Wu, Meng; McNulty, Nathan P.; Rodionov, Dmitry A.; Khoroshkin, Matvei S.; Griffin, Nicholas W.; Cheng, Jiye; Latreille, Phil; Kerstetter, Randall A.; Terrapon, Nicolas; Henrissat, Bernard; Osterman, Andrei L.; Gordon, Jeffrey I.

    2015-01-01

    Libraries of tens of thousands of transposon mutants generated from each of four human gut Bacteroides strains, two representing the same species, were introduced simultaneously into gnotobiotic mice together with 11 other wild-type strains to generate a 15-member artificial human gut microbiota. Mice received one of two distinct diets monotonously, or both in ordered sequence. Quantifying the abundance of mutants in different diet contexts allowed gene-level characterization of fitness determinants, niche, stability and resilience, and yielded a prebiotic (arabinoxylan) that allowed targeted manipulation of the community. The approach described is generalizable and should be useful for defining mechanisms critical for sustaining and/or approaches for deliberately reconfiguring the highly adaptive and durable relationship between the human gut microbiota and host in ways that promote wellness. PMID:26430127

  5. The Human Gut Microbiome and Body Metabolism: Implications for Obesity and Diabetes

    PubMed Central

    Devaraj, Sridevi; Hemarajata, Peera; Versalovic, James

    2014-01-01

    BACKGROUND Obesity, metabolic syndrome, and type 2 diabetes are major public health challenges. Recently, interest has surged regarding the possible role of the intestinal microbiota as potential novel contributors to the increased prevalence of these 3 disorders. CONTENT Recent advances in microbial DNA sequencing technologies have resulted in the widespread application of whole-genome sequencing technologies for metagenomic DNA analysis of complex ecosystems such as the human gut. Current evidence suggests that the gut microbiota affect nutrient acquisition, energy harvest, and a myriad of host metabolic pathways. CONCLUSION Advances in the Human Microbiome Project and human metagenomics research will lead the way toward a greater understanding of the importance and role of the gut microbiome in metabolic disorders such as obesity, metabolic syndrome, and diabetes. PMID:23401286

  6. Human nutrition, the gut microbiome and the immune system.

    PubMed

    Kau, Andrew L; Ahern, Philip P; Griffin, Nicholas W; Goodman, Andrew L; Gordon, Jeffrey I

    2011-06-16

    Marked changes in socio-economic status, cultural traditions, population growth and agriculture are affecting diets worldwide. Understanding how our diet and nutritional status influence the composition and dynamic operations of our gut microbial communities, and the innate and adaptive arms of our immune system, represents an area of scientific need, opportunity and challenge. The insights gleaned should help to address several pressing global health problems.

  7. Human Gut Microbiota Changes Reveal the Progression of Glucose Intolerance

    PubMed Central

    Zhang, Xiuying; Shen, Dongqian; Fang, Zhiwei; Jie, Zhuye; Qiu, Xinmin; Zhang, Chunfang; Chen, Yingli; Ji, Linong

    2013-01-01

    To explore the relationship of gut microbiota with the development of type 2 diabetes (T2DM), we analyzed 121 subjects who were divided into 3 groups based on their glucose intolerance status: normal glucose tolerance (NGT; n = 44), prediabetes (Pre-DM; n = 64), or newly diagnosed T2DM (n = 13). Gut microbiota characterizations were determined with 16S rDNA-based high-throughput sequencing. T2DM-related dysbiosis was observed, including the separation of microbial communities and a change of alpha diversity between the different glucose intolerance statuses. To assess the correlation between metabolic parameters and microbiota diversity, clinical characteristics were also measured and a significant association between metabolic parameters (FPG, CRP) and gut microbiota was found. In addition, a total of 28 operational taxonomic units (OTUs) were found to be related to T2DM status by the Kruskal-Wallis H test, most of which were enriched in the T2DM group. Butyrate-producing bacteria (e.g. Akkermansia muciniphila ATCCBAA-835, and Faecalibacterium prausnitzii L2-6) had a higher abundance in the NGT group than in the pre-DM group. At genus level, the abundance of Bacteroides in the T2DM group was only half that of the NGT and Pre-DM groups. Previously reported T2DM-related markers were also compared with the data in this study, and some inconsistencies were noted. We found that Verrucomicrobiae may be a potential marker of T2DM as it had a significantly lower abundance in both the pre-DM and T2DM groups. In conclusion, this research provides further evidence of the structural modulation of gut microbiota in the pathogenesis of diabetes. PMID:24013136

  8. Human Milk Glycomics and Gut Microbial Genomics in Infant Feces Show a Correlation between Human Milk Oligosaccharides and Gut Microbiota: A Proof-of-Concept Study

    PubMed Central

    2015-01-01

    Human milk oligosaccharides (HMOs) play a key role in shaping and maintaining a healthy infant gut microbiota. This article demonstrates the potential of combining recent advances in glycomics and genomics to correlate abundances of fecal microbes and fecal HMOs. Serial fecal specimens from two healthy breast-fed infants were analyzed by bacterial DNA sequencing to characterize the microbiota and by mass spectrometry to determine abundances of specific HMOs that passed through the intestinal tract without being consumed by the luminal bacteria. In both infants, the fecal bacterial population shifted from non-HMO-consuming microbes to HMO-consuming bacteria during the first few weeks of life. An initial rise in fecal HMOs corresponded with bacterial populations composed primarily of non-HMO-consuming Enterobacteriaceae and Staphylococcaeae. This was followed by decreases in fecal HMOs as the proportion of HMO-consuming Bacteroidaceae and Bifidobacteriaceae increased. Analysis of HMO structures with isomer differentiation revealed that HMO consumption is highly structure-specific, with unique isomers being consumed and others passing through the gut unaltered. These results represent a proof-of-concept and are consistent with the highly selective, prebiotic effect of HMOs in shaping the gut microbiota in the first weeks of life. The analysis of selective fecal bacterial substrates as a measure of alterations in the gut microbiota may be a potential marker of dysbiosis. PMID:25300177

  9. Probiotics and virulent human rotavirus modulate the transplanted human gut microbiota in gnotobiotic pigs.

    PubMed

    Zhang, Husen; Wang, Haifeng; Shepherd, Megan; Wen, Ke; Li, Guohua; Yang, Xingdong; Kocher, Jacob; Giri-Rachman, Ernawati; Dickerman, Allan; Settlage, Robert; Yuan, Lijuan

    2014-01-01

    We generated a neonatal pig model with human infant gut microbiota (HGM) to study the effect of a probiotic on the composition of the transplanted microbiota following rotavirus vaccination and challenge. All the HGM-transplanted pigs received two doses of an oral attenuated rotavirus vaccine. The gut microbiota of vaccinated pigs were investigated for effects of Lactobacillus rhamnosus GG (LGG) supplement and homotypic virulent human rotavirus (HRV) challenge. High-throughput sequencing of V4 region of 16S rRNA genes demonstrated that HGM-transplanted pigs carried microbiota similar to that of the C-section delivered baby. Firmicutes and Proteobacteria represented over 98% of total bacteria in the human donor and the recipient pigs. HRV challenge caused a phylum-level shift from Firmicutes to Proteobacteria. LGG supplement prevented the changes in microbial communities caused by HRV challenge. In particular, members of Enterococcus in LGG-supplemented pigs were kept at the baseline level, while they were enriched in HRV challenged pigs. Taken together, our results suggested that HGM pigs are valuable for testing the microbiota's response to probiotic interventions for treating infantile HRV infection. PMID:25349634

  10. Probiotics and virulent human rotavirus modulate the transplanted human gut microbiota in gnotobiotic pigs

    PubMed Central

    2014-01-01

    We generated a neonatal pig model with human infant gut microbiota (HGM) to study the effect of a probiotic on the composition of the transplanted microbiota following rotavirus vaccination and challenge. All the HGM-transplanted pigs received two doses of an oral attenuated rotavirus vaccine. The gut microbiota of vaccinated pigs were investigated for effects of Lactobacillus rhamnosus GG (LGG) supplement and homotypic virulent human rotavirus (HRV) challenge. High-throughput sequencing of V4 region of 16S rRNA genes demonstrated that HGM-transplanted pigs carried microbiota similar to that of the C-section delivered baby. Firmicutes and Proteobacteria represented over 98% of total bacteria in the human donor and the recipient pigs. HRV challenge caused a phylum-level shift from Firmicutes to Proteobacteria. LGG supplement prevented the changes in microbial communities caused by HRV challenge. In particular, members of Enterococcus in LGG-supplemented pigs were kept at the baseline level, while they were enriched in HRV challenged pigs. Taken together, our results suggested that HGM pigs are valuable for testing the microbiota’s response to probiotic interventions for treating infantile HRV infection. PMID:25349634

  11. Genetic and transcriptional analysis of human host response to healthy gut microbiota

    PubMed Central

    Richards, Allison L.; Burns, Michael B.; Alazizi, Adnan; Barreiro, Luis B.; Pique-Regi, Roger; Blekhman, Ran; Luca, Francesca

    2016-01-01

    Many studies have demonstrated the importance of the gut microbiota in healthy and disease states. However, establishing the causality of host-microbiota interactions in humans is still challenging. Here, we describe a novel experimental system to define the transcriptional response induced by the microbiota in human cells and to shed light on the molecular mechanisms underlying host-gut microbiota interactions. In primary human colonic epithelial cells, we identified over 6,000 genes that change expression at various time points following co-culturing with the gut microbiota of a healthy individual. Among the differentially expressed genes we found a 1.8-fold enrichment of genes associated with diseases that have been previously linked to the microbiome, such as obesity and colorectal cancer. In addition, our experimental system allowed us to identify 87 host SNPs that show allele-specific expression in 69 genes. Furthermore, for 12 SNPs in 12 different genes, allele-specific expression is conditional on the exposure to the microbiota. Of these 12 genes, eight have been associated with diseases linked to the gut microbiota, specifically colorectal cancer, obesity and type 2 diabetes. Our study demonstrates a scalable approach to study host-gut microbiota interactions and can be used to identify putative mechanisms for the interplay between host genetics and microbiota in health and disease. PMID:27709125

  12. Genetic and transcriptional analysis of human host response to healthy gut microbiota

    PubMed Central

    Richards, Allison L.; Burns, Michael B.; Alazizi, Adnan; Barreiro, Luis B.; Pique-Regi, Roger; Blekhman, Ran; Luca, Francesca

    2016-01-01

    Many studies have demonstrated the importance of the gut microbiota in healthy and disease states. However, establishing the causality of host-microbiota interactions in humans is still challenging. Here, we describe a novel experimental system to define the transcriptional response induced by the microbiota in human cells and to shed light on the molecular mechanisms underlying host-gut microbiota interactions. In primary human colonic epithelial cells, we identified over 6,000 genes that change expression at various time points following co-culturing with the gut microbiota of a healthy individual. Among the differentially expressed genes we found a 1.8-fold enrichment of genes associated with diseases that have been previously linked to the microbiome, such as obesity and colorectal cancer. In addition, our experimental system allowed us to identify 87 host SNPs that show allele-specific expression in 69 genes. Furthermore, for 12 SNPs in 12 different genes, allele-specific expression is conditional on the exposure to the microbiota. Of these 12 genes, eight have been associated with diseases linked to the gut microbiota, specifically colorectal cancer, obesity and type 2 diabetes. Our study demonstrates a scalable approach to study host-gut microbiota interactions and can be used to identify putative mechanisms for the interplay between host genetics and microbiota in health and disease.

  13. Fate, activity, and impact of ingested bacteria within the human gut microbiota.

    PubMed

    Derrien, Muriel; van Hylckama Vlieg, Johan E T

    2015-06-01

    The human gut contains a highly diverse microbial community that is essentially an open ecosystem, despite being deeply embedded within the human body. Food-associated fermentative bacteria, including probiotics, are major sources of ingested bacteria that may temporarily complement resident microbial communities, thus forming part of our transient microbiome. Here, we review data on the fate and activity of ingested bacteria and, in particular, lactobacilli and bifidobacteria in the gastrointestinal (GI) tract and their impact on the composition and metabolism of the gut microbiome with a focus on data from clinical studies. In addition, we discuss the mechanisms involved and the potential impact on the host's health. PMID:25840765

  14. Functional metagenomics to mine the human gut microbiome for dietary fiber catabolic enzymes.

    PubMed

    Tasse, Lena; Bercovici, Juliette; Pizzut-Serin, Sandra; Robe, Patrick; Tap, Julien; Klopp, Christophe; Cantarel, Brandi L; Coutinho, Pedro M; Henrissat, Bernard; Leclerc, Marion; Doré, Joël; Monsan, Pierre; Remaud-Simeon, Magali; Potocki-Veronese, Gabrielle

    2010-11-01

    The human gut microbiome is a complex ecosystem composed mainly of uncultured bacteria. It plays an essential role in the catabolism of dietary fibers, the part of plant material in our diet that is not metabolized in the upper digestive tract, because the human genome does not encode adequate carbohydrate active enzymes (CAZymes). We describe a multi-step functionally based approach to guide the in-depth pyrosequencing of specific regions of the human gut metagenome encoding the CAZymes involved in dietary fiber breakdown. High-throughput functional screens were first applied to a library covering 5.4 × 10(9) bp of metagenomic DNA, allowing the isolation of 310 clones showing beta-glucanase, hemicellulase, galactanase, amylase, or pectinase activities. Based on the results of refined secondary screens, sequencing efforts were reduced to 0.84 Mb of nonredundant metagenomic DNA, corresponding to 26 clones that were particularly efficient for the degradation of raw plant polysaccharides. Seventy-three CAZymes from 35 different families were discovered. This corresponds to a fivefold target-gene enrichment compared to random sequencing of the human gut metagenome. Thirty-three of these CAZy encoding genes are highly homologous to prevalent genes found in the gut microbiome of at least 20 individuals for whose metagenomic data are available. Moreover, 18 multigenic clusters encoding complementary enzyme activities for plant cell wall degradation were also identified. Gene taxonomic assignment is consistent with horizontal gene transfer events in dominant gut species and provides new insights into the human gut functional trophic chain.

  15. Transfer of plasmid-mediated CTX-M-9 from Salmonella enterica serotype Virchow to Enterobacteriaceae in human flora-associated rats treated with cefixime.

    PubMed

    Faure, S; Perrin-Guyomard, A; Delmas, J M; Chatre, P; Laurentie, M

    2010-01-01

    Food animals are a potential source of CTX-M resistance genes for humans. We evaluated the transfer of the bla(CTX-M-9) gene from an animal strain of Salmonella enterica serotype Virchow to Enterobacteriaceae of the human intestinal flora by using human flora-associated (HFA) rats with and without cefixime treatment. In the absence of antibiotic, no transconjugant enterobacteria were found in the feces of HFA rats. However, the transfer rate was high if Escherichia coli J5 recipient strains were coinoculated orally with Salmonella. S. enterica serotype Virchow persisted in the rat fecal flora both during and after treatment with therapeutic doses of cefixime. The drug did not increase the transfer rate, and E. coli J5 transconjugants were eliminated from the flora before the end of cefixime treatment. No cefixime was recovered in the rat feces. In the presence of recipient strains, the bla(CTX-M-9) resistance gene was transferred from a strain of animal origin to the human intestinal flora, although transconjugant colonization was transient. Antibiotic use enhanced the persistence of donor strains, increasing the resistance gene pool and the risk of its spread.

  16. The Yin and Yang of Bacterial Resilience in the Human Gut Microbiota

    PubMed Central

    Gibson, Molly K.; Pesesky, Mitchell W.; Dantas, Gautam

    2014-01-01

    The human gut is home to trillions of microbes that form a symbiotic relationship with the human host. During health, the intestinal microbiota provides many benefits to the host and is generally resistant to colonization by new species; however, disruption of this complex community can lead to pathogen invasion, inflammation, and disease. Restoration and maintenance of a healthy gut microbiota composition requires effective therapies to reduce and prevent colonization of harmful bacteria (pathogens) while simultaneously promoting growth of beneficial bacteria (probiotics). Here we review the mechanisms by which the host modulates the gut community composition during health and disease, and discuss prospects for antibiotic and probiotic therapy for restoration of a healthy intestinal community following disruption. PMID:24911583

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

    SciTech Connect

    Koropatkin, Nicole M.; Martens, Eric C.; Gordon, Jeffrey I.; Smith, Thomas J.

    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.

  18. Human fecal flora: variation in bacterial composition within individuals and a possible effect of emotional stress.

    PubMed Central

    Holdeman, L V; Good, I J; Moore, W E

    1976-01-01

    Data are presented on the distribution of 101 bacterial species and subspecies among 1,442 isolates from 25 fecal specimens from three men on: (i) their normal diet and normal living conditions, (ii) normal living conditions but eating the controlled metabolic diet designed for use in the Skylab simulation and missions, and (iii) the Skylab diet in simulated Skylab (isolation) conditions. These bacteria represent the most numerous kinds in the fecal flora. Analyses of the kinds of bacteria from each astronaut during the 5-month period showed more variation in the composition of the flora among the individual astronauts than among the eight or nine samples from each person. This observation indicates that the variations in fecal flora reported previously, but based on the study of only one specimen from each person, more certainly reflect real differences (and not daily variation) in the types of bacteria maintained by individual people. The proportions of the predominant fecal species in the astronauts were similar to those reported earlier from a Japanese-Hawaiian population and were generally insensitive to changes from the normal North American diet to the Skylab diet; only two of the most common species were affected by changes in diet. However, one of the predominant species (Bacteroides fragilis subsp. thetaiotaomicron) appeared to be affected during confinement of the men in the Skylab test chamber. Evidence is presented suggesting that an anger stress situation may have been responsible for the increase of this species simultaneously in all of the subjects studied. Phenotypic characteristics of some of the less common isolates are given. The statistical analyses used in interpretation of the results are discussed. PMID:938032

  19. Role of gut microbiota in obesity, type 2 diabetes and Alzheimer's disease.

    PubMed

    Naseer, Muhammad I; Bibi, Fehmida; Alqahtani, Mohammed H; Chaudhary, Adeel G; Azhar, Esam I; Kamal, Mohammad A; Yasir, Muhammad

    2014-03-01

    In recent years, there is a growing interest in research to investigate the importance of gut microbiome in health and diseases. This opens a new area of research for the role of microbial flora of the human gut in inflammation, energy homeostasis, pathogenesis of obesity and other associated disorders. Recent studies propose association of the gut microbiome with development of obesity and metabolic syndromes, such as type 2 diabetes mellitus (T2DM). The T2DM is a metabolic disease that is mainly caused by obesity-linked insulin resistance. The vascular effects of obesity appears to play a role in the development of Alzheimer's disease (AD) that is one of the rapidly growing diseases of a late stage of life all over the world. Studies from both humans and mice models have been demonstrated the engagement of gut microbial flora in the pathogenesis of obesity and host metabolism. The aim of this review is to discuss the current findings that may explain the cascade of gut microbial flora participation in the development of obesity, T2DM and further initiation of AD. In addition, the available data regarding the mechanisms that have been proposed to elucidate the role of gut microbiota in weight gain and possible cause of T2DM and AD have been examined.

  20. Nitrogen fixation and nifH diversity in human gut microbiota.

    PubMed

    Igai, Katsura; Itakura, Manabu; Nishijima, Suguru; Tsurumaru, Hirohito; Suda, Wataru; Tsutaya, Takumi; Tomitsuka, Eriko; Tadokoro, Kiyoshi; Baba, Jun; Odani, Shingo; Natsuhara, Kazumi; Morita, Ayako; Yoneda, Minoru; Greenhill, Andrew R; Horwood, Paul F; Inoue, Jun-Ichi; Ohkuma, Moriya; Hongoh, Yuichi; Yamamoto, Taro; Siba, Peter M; Hattori, Masahira; Minamisawa, Kiwamu; Umezaki, Masahiro

    2016-01-01

    It has been hypothesized that nitrogen fixation occurs in the human gut. However, whether the gut microbiota truly has this potential remains unclear. We investigated the nitrogen-fixing activity and diversity of the nitrogenase reductase (NifH) genes in the faecal microbiota of humans, focusing on Papua New Guinean and Japanese individuals with low to high habitual nitrogen intake. A (15)N2 incorporation assay showed significant enrichment of (15)N in all faecal samples, irrespective of the host nitrogen intake, which was also supported by an acetylene reduction assay. The fixed nitrogen corresponded to 0.01% of the standard nitrogen requirement for humans, although our data implied that the contribution in the gut in vivo might be higher than this value. The nifH genes recovered in cloning and metagenomic analyses were classified in two clusters: one comprising sequences almost identical to Klebsiella sequences and the other related to sequences of Clostridiales members. These results are consistent with an analysis of databases of faecal metagenomes from other human populations. Collectively, the human gut microbiota has a potential for nitrogen fixation, which may be attributable to Klebsiella and Clostridiales strains, although no evidence was found that the nitrogen-fixing activity substantially contributes to the host nitrogen balance. PMID:27554344

  1. Nitrogen fixation and nifH diversity in human gut microbiota.

    PubMed

    Igai, Katsura; Itakura, Manabu; Nishijima, Suguru; Tsurumaru, Hirohito; Suda, Wataru; Tsutaya, Takumi; Tomitsuka, Eriko; Tadokoro, Kiyoshi; Baba, Jun; Odani, Shingo; Natsuhara, Kazumi; Morita, Ayako; Yoneda, Minoru; Greenhill, Andrew R; Horwood, Paul F; Inoue, Jun-Ichi; Ohkuma, Moriya; Hongoh, Yuichi; Yamamoto, Taro; Siba, Peter M; Hattori, Masahira; Minamisawa, Kiwamu; Umezaki, Masahiro

    2016-08-24

    It has been hypothesized that nitrogen fixation occurs in the human gut. However, whether the gut microbiota truly has this potential remains unclear. We investigated the nitrogen-fixing activity and diversity of the nitrogenase reductase (NifH) genes in the faecal microbiota of humans, focusing on Papua New Guinean and Japanese individuals with low to high habitual nitrogen intake. A (15)N2 incorporation assay showed significant enrichment of (15)N in all faecal samples, irrespective of the host nitrogen intake, which was also supported by an acetylene reduction assay. The fixed nitrogen corresponded to 0.01% of the standard nitrogen requirement for humans, although our data implied that the contribution in the gut in vivo might be higher than this value. The nifH genes recovered in cloning and metagenomic analyses were classified in two clusters: one comprising sequences almost identical to Klebsiella sequences and the other related to sequences of Clostridiales members. These results are consistent with an analysis of databases of faecal metagenomes from other human populations. Collectively, the human gut microbiota has a potential for nitrogen fixation, which may be attributable to Klebsiella and Clostridiales strains, although no evidence was found that the nitrogen-fixing activity substantially contributes to the host nitrogen balance.

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

    PubMed Central

    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. PMID:25656825

  3. Nitrogen fixation and nifH diversity in human gut microbiota

    PubMed Central

    Igai, Katsura; Itakura, Manabu; Nishijima, Suguru; Tsurumaru, Hirohito; Suda, Wataru; Tsutaya, Takumi; Tomitsuka, Eriko; Tadokoro, Kiyoshi; Baba, Jun; Odani, Shingo; Natsuhara, Kazumi; Morita, Ayako; Yoneda, Minoru; Greenhill, Andrew R.; Horwood, Paul F.; Inoue, Jun-ichi; Ohkuma, Moriya; Hongoh, Yuichi; Yamamoto, Taro; Siba, Peter M.; Hattori, Masahira; Minamisawa, Kiwamu; Umezaki, Masahiro

    2016-01-01

    It has been hypothesized that nitrogen fixation occurs in the human gut. However, whether the gut microbiota truly has this potential remains unclear. We investigated the nitrogen-fixing activity and diversity of the nitrogenase reductase (NifH) genes in the faecal microbiota of humans, focusing on Papua New Guinean and Japanese individuals with low to high habitual nitrogen intake. A 15N2 incorporation assay showed significant enrichment of 15N in all faecal samples, irrespective of the host nitrogen intake, which was also supported by an acetylene reduction assay. The fixed nitrogen corresponded to 0.01% of the standard nitrogen requirement for humans, although our data implied that the contribution in the gut in vivo might be higher than this value. The nifH genes recovered in cloning and metagenomic analyses were classified in two clusters: one comprising sequences almost identical to Klebsiella sequences and the other related to sequences of Clostridiales members. These results are consistent with an analysis of databases of faecal metagenomes from other human populations. Collectively, the human gut microbiota has a potential for nitrogen fixation, which may be attributable to Klebsiella and Clostridiales strains, although no evidence was found that the nitrogen-fixing activity substantially contributes to the host nitrogen balance. PMID:27554344

  4. Characterizing a model human gut microbiota composed of members of its two dominant bacterial phyla

    SciTech Connect

    Mahowald, Michael; Rey, Frederico E.; Seedorf, Henning; Turnbaugh, Peter J.; Fulton, Robert S.; Wollam, Aye; Shah, Neha; Wang, Chunyan; Magrini, Vincent; Wilson, Richard K.; Cantarel, Brandi L.; Coutinho, Pedro M; Henrissat, Bernard; Crock, Lara W.; Verberkmoes, Nathan C; Hettich, Robert {Bob} L; Erickson, Alison L; Gordon, Jeffrey

    2009-01-01

    The adult human distal gut microbial community is typically dominated by 2 bacterial phyla (divisions), the Firmicutes and the Bacteroidetes. Little is known about the factors that govern the interactions between their members. Here, we examine the niches of representatives of both phyla in vivo. Finished genome sequences were generated from Eubacterium rectale and E. eligens, which belong to Clostridium Cluster XIVa, one of the most common gut Firmicute clades. Comparison of these and 25 other gut Firmicutes and Bacteroidetes indicated that the Firmicutes possess smaller genomes and a disproportionately smaller number of glycan-degrading enzymes. Germ-free mice were then colonized with E. rectale and/or a prominent human gut Bacteroidetes, Bacteroides thetaiotaomicron, followed by whole-genome transcriptional profiling, high-resolution proteomic analysis, and biochemical assays of microbial microbial and microbial host interactions. B. thetaiotaomicron adapts to E. rectale by up-regulating expression of a variety of polysaccharide utilization loci encoding numerous glycoside hydrolases, and by signaling the host to produce mucosal glycans that it, but not E. rectale, can access. E. rectale adapts to B. thetaiotaomicron by decreasing production of its glycan-degrading enzymes, increasing expression of selected amino acid and sugar transporters, and facilitating glycolysis by reducing levels of NADH, in part via generation of butyrate from acetate, which in turn is used by the gut epithelium. This simplified model of the human gut microbiota illustrates niche specialization and functional redundancy within members of its major bacterial phyla, and the importance of host glycans as a nutrient foundation that ensures ecosystem stability.

  5. Translational research into gut microbiota: new horizons on obesity treatment: updated 2014.

    PubMed

    Tsukumo, Daniela M; Carvalho, Bruno M; Carvalho Filho, Marco A; Saad, Mário J A

    2015-04-01

    Obesity is currently a pandemic of worldwide proportions affecting millions of people. Recent studies have proposed the hypothesis that mechanisms not directly related to the human genome could be involved in the genesis of obesity, due to the fact that, when a population undergoes the same nutritional stress, not all individuals present weight gain related to the diet or become hyperglycemic. The human intestine is colonized by millions of bacteria which form the intestinal flora, known as gut flora. Studies show that lean and overweight human may present a difference in the composition of their intestinal flora; these studies suggest that the intestinal flora could be involved in the development of obesity. Several mechanisms explain the correlation between intestinal flora and obesity. The intestinal flora would increase the energetic extraction of non-digestible polysaccharides. In addition, the lipopolysaccharide from intestinal flora bacteria could trigger a chronic sub-clinical inflammatory process, leading to obesity and diabetes. Another mechanism through which the intestinal flora could lead to obesity would be through the regulation of genes of the host involved in energy storage and expenditure. In the past five years data coming from different sources established causal effects between intestinal microbiota and obesity/insulin resistance, and it is clear that this area will open new avenues of therapeutic to obesity, insulin resistance and DM2.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  7. In vitro fermentation patterns of rice bran components by human gut microbiota

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Rice bran is a rich source of bioactive components that can promote gastrointestinal health. However, bran is removed during polishing. Among those, feruloylated arabinoxylan oligosaccharides (FAXO) and rice bran polyphenolics (RBPP) are hypothesized to have positive impacts on human gut microbiota ...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  9. The long-term stability of the human gut microbiota

    PubMed Central

    Faith, Jeremiah J.; Guruge, Janaki L.; Charbonneau, Mark; Subramanian, Sathish; Seedorf, Henning; Goodman, Andrew L.; Clemente, Jose C.; Knight, Rob; Heath, Andrew C.; Leibel, Rudolph L.; Rosenbaum, Michael; Gordon, Jeffrey I.

    2013-01-01

    A low-error 16S rRNA amplicon sequencing method (LEA-Seq) plus whole genome sequencing of >500 cultured isolates were used to characterize bacterial strain composition in the fecal microbiota of 37 USA adults sampled for up to five years. Microbiota stability follows a power law function which, when extrapolated, suggests that most strains in an individual are residents for decades. Shared strains were recovered from family members, but not from unrelated individuals. Sampling individuals for up to 32 weeks while consuming a monotonous liquid diet indicated that changes in weight are more predictive of changes in strain composition than sampling interval. This combination of stability and responsiveness to physiologic change confirms the potential of the gut microbiota as a diagnostic tool and therapeutic target. PMID:23828941

  10. Towards predictive models of the human gut microbiome

    PubMed Central

    2014-01-01

    The intestinal microbiota is an ecosystem susceptible to external perturbations such as dietary changes and antibiotic therapies. Mathematical models of microbial communities could be of great value in the rational design of microbiota-tailoring diets and therapies. Here, we discuss how advances in another field, engineering of microbial communities for wastewater treatment bioreactors, could inspire development of mechanistic mathematical models of the gut microbiota. We review the current state-of-the-art in bioreactor modeling and current efforts in modeling the intestinal microbiota. Mathematical modeling could benefit greatly from the deluge of data emerging from metagenomic studies, but data-driven approaches such as network inference that aim to predict microbiome dynamics without explicit mechanistic knowledge seem better suited to model these data. Finally, we discuss how the integration of microbiome shotgun sequencing and metabolic modeling approaches such as flux balance analysis may fulfill the promise of a mechanistic model of the intestinal microbiota. PMID:24727124

  11. Gut microbiota and liver disease.

    PubMed

    Goel, Amit; Gupta, Mahesh; Aggarwal, Rakesh

    2014-06-01

    Microbes are present in large numbers in each human being, in particularly in the gastrointestinal (GI) tract, and have long been believed to have some beneficial effects for their hosts. Till recently, however, we lacked tools for studying these organisms. Rapid technological advances in recent years have markedly improved our understanding of their role both in health and disease. Recent literature suggests that organisms in the GI tract, referred to collectively as gut microbiota, play an indispensable role in the maintenance of host's homeostasis. Alterations in the gut microbiota, that is in the nature and relative density of various constituent bacterial species, appear to have a role in pathogenesis and progression of several GI and hepatic diseases. This has also opened the vista for tinkering with gut flora in an attempt to treat or prevent such diseases. In this review, we have tried to summarize information on normal gut microbiota, laboratory techniques and animal models used to study it, and the role of its perturbations in some of the common hepatic disorders, such as non-alcoholic fatty liver disease (including obesity), non-alcoholic steatohepatitis, alcoholic liver disease, and liver cirrhosis and its complications.

  12. Roles of UGT, P450, and Gut Microbiota in the Metabolism of Epacadostat in Humans.

    PubMed

    Boer, Jason; Young-Sciame, Ruth; Lee, Fiona; Bowman, Kevin J; Yang, Xiaoqing; Shi, Jack G; Nedza, Frank M; Frietze, William; Galya, Laurine; Combs, Andrew P; Yeleswaram, Swamy; Diamond, Sharon

    2016-10-01

    Epacadostat (EPA, INCB024360) is a first-in-class, orally active, investigational drug targeting the enzyme indoleamine 2,3-dioxygenase 1 (IDO1). In Phase I studies, EPA has demonstrated promising clinical activity when used in combination with checkpoint modulators. When the metabolism of EPA was investigated in humans, three major, IDO1-inactive, circulating plasma metabolites were detected and characterized: M9, a direct O-glucuronide of EPA; M11, an amidine; and M12, N-dealkylated M11. Glucuronidation of EPA to form M9 is the dominant metabolic pathway, and in vitro, this metabolite is formed by UGT1A9. However, negligible quantities of M11 and M12 were detected when EPA was incubated with a panel of human microsomes from multiple tissues, hepatocytes, recombinant human cytochrome P450s (P450s), and non-P450 enzymatic systems. Given the reductive nature of M11 formation and the inability to define its source, the role of gut microbiota was investigated. Analysis of plasma from mice dosed with EPA following pretreatment with either antibiotic (ciprofloxacin) to inhibit gut bacteria or 1-aminobenzotriazole (ABT) to systemically inhibit P450s demonstrated that gut microbiota is responsible for the formation of M11. Incubations of EPA in human feces confirmed the role of gut bacteria in the formation of M11. Further, incubations of M11 with recombinant P450s showed that M12 is formed via N-dealkylation of M11 by CYP3A4, CYP2C19, and CYP1A2. Thus, in humans three major plasma metabolites of EPA were characterized: two primary metabolites, M9 and M11, formed directly from EPA via UGT1A9 and gut microbiota, respectively, and M12 formed as a secondary metabolite via P450s from M11.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  14. Gut check: testing a role for the intestinal microbiome in human obesity.

    PubMed

    Flier, Jeffrey S; Mekalanos, John J

    2009-11-11

    By using germ-free mice transplanted with human fecal microbiota, scientists show that a high-fat, high-sugar diet durably changes the transplanted microbiome and that this diet-altered microbiome promotes obesity. This model should encourage investigation of the gut microbiome as a contributor to human metabolic disease and permit discovery of targets for the prevention and treatment of these disorders. PMID:20368177

  15. Obesity pandemics and the modification of digestive bacterial flora.

    PubMed

    Raoult, D

    2008-08-01

    Environmental factors, such as social networks, have an influence on obesity pandemics. The gut microbial flora (microbiota) plays a role in converting nutrients into calories. Variations in microbiota composition are found in obese humans and mice. The microbiota from an obese mouse confers an obese phenotype when transferred to an axenic mouse. There is a large body of experimental evidence and empirical data in the food industry showing that both antibiotics and probiotics, which modify the gut microbiota, can act as growth promoters, increasing the size and weight of animals. The current obesity pandemic may be caused, in part, by antibiotic treatments or colonization by probiotic bacteria. Using metagenomics and microarray analysis, studies of microbiota modifications after antibiotic and probiotic intake may identify the modifications associated with increased size and weight. Epidemiological studies recording these factors in an obese population may be able to link obesity with the absorption of microbiota modifiers.

  16. Metabolic modeling of common Escherichia coli strains in human gut microbiome.

    PubMed

    Gao, Yue-Dong; Zhao, Yuqi; Huang, Jingfei

    2014-01-01

    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.

  17. Coordinate regulation of glycan degradation and polysaccharide capsule biosynthesis by a prominent human gut symbiont.

    PubMed

    Martens, Eric C; Roth, Robyn; Heuser, John E; Gordon, Jeffrey I

    2009-07-01

    Bacteria in the distal human gut have evolved diverse abilities to metabolize complex glycans, including the capacity to degrade these compounds as nutrients and to assemble their component sugars into new polymers such as extracellular capsules. The human gut bacterium Bacteroides thetaiotaomicron is well endowed with the ability to metabolize both host- and diet-derived glycans. Its genome contains 88 different polysaccharide utilization loci (PULs) for complex glycan catabolism and eight different gene clusters for capsular polysaccharide biosynthesis. Here, we investigate one of the prominent mechanisms by which this gut symbiont regulates many PULs involved in host mucin O-glycan degradation; namely, transcriptional regulation via the concerted interactions of cell-envelope-localized TonB-dependent transporters, extra-cytoplasmic function sigma factors and anti-sigma factors, which participate together in a regulatory pathway termed trans-envelope signaling. Unexpectedly, we found that several different trans-envelope signaling switches involved in PUL-mediated O-glycan degradation also modulate capsular polysaccharide synthesis. A novel regulatory pathway, which is dependent on expression of O-glycan-targeting outer membrane proteins, governs this coordinated regulation of glycan catabolism and capsule synthesis. This latter finding provides a new link in the dynamic interplay between complex glycan metabolism, microbial physiology, and host responses that occurs during colonization of the gut.

  18. Colonization with the enteric protozoa Blastocystis is associated with increased diversity of human gut bacterial microbiota.

    PubMed

    Audebert, Christophe; Even, Gaël; Cian, Amandine; Loywick, Alexandre; Merlin, Sophie; Viscogliosi, Eric; Chabé, Magali

    2016-01-01

    Alterations in the composition of commensal bacterial populations, a phenomenon known as dysbiosis, are linked to multiple gastrointestinal disorders, such as inflammatory bowel disease and irritable bowel syndrome, or to infections by diverse enteric pathogens. Blastocystis is one of the most common single-celled eukaryotes detected in human faecal samples. However, the clinical significance of this widespread colonization remains unclear, and its pathogenic potential is controversial. To address the issue of Blastocystis pathogenicity, we investigated the impact of colonization by this protist on the composition of the human gut microbiota. For that purpose, we conducted a cross-sectional study including 48 Blastocystis-colonized patients and 48 Blastocystis-free subjects and performed an Ion Torrent 16S rDNA gene sequencing to decipher the Blastocystis-associated gut microbiota. Here, we report a higher bacterial diversity in faecal microbiota of Blastocystis colonized patients, a higher abundance of Clostridia as well as a lower abundance of Enterobacteriaceae. Our results contribute to suggesting that Blastocystis colonization is usually associated with a healthy gut microbiota, rather than with gut dysbiosis generally observed in metabolic or infectious inflammatory diseases of the lower gastrointestinal tract. PMID:27147260

  19. Colonization with the enteric protozoa Blastocystis is associated with increased diversity of human gut bacterial microbiota

    PubMed Central

    Audebert, Christophe; Even, Gaël; Cian, Amandine; Safadi, Dima El; Certad, Gabriela; Delhaes, Laurence; Pereira, Bruno; Nourrisson, Céline; Poirier, Philippe; Wawrzyniak, Ivan; Delbac, Frédéric; Morelle, Christelle; Bastien, Patrick; Lachaud, Laurence; Bellanger, Anne-Pauline; Botterel, Françoise; Candolfi, Ermanno; Desoubeaux, Guillaume; Morio, Florent; Pomares, Christelle; Rabodonirina, Meja; Loywick, Alexandre; Merlin, Sophie; Viscogliosi, Eric; Chabé, Magali

    2016-01-01

    Alterations in the composition of commensal bacterial populations, a phenomenon known as dysbiosis, are linked to multiple gastrointestinal disorders, such as inflammatory bowel disease and irritable bowel syndrome, or to infections by diverse enteric pathogens. Blastocystis is one of the most common single-celled eukaryotes detected in human faecal samples. However, the clinical significance of this widespread colonization remains unclear, and its pathogenic potential is controversial. To address the issue of Blastocystis pathogenicity, we investigated the impact of colonization by this protist on the composition of the human gut microbiota. For that purpose, we conducted a cross-sectional study including 48 Blastocystis-colonized patients and 48 Blastocystis-free subjects and performed an Ion Torrent 16S rDNA gene sequencing to decipher the Blastocystis-associated gut microbiota. Here, we report a higher bacterial diversity in faecal microbiota of Blastocystis colonized patients, a higher abundance of Clostridia as well as a lower abundance of Enterobacteriaceae. Our results contribute to suggesting that Blastocystis colonization is usually associated with a healthy gut microbiota, rather than with gut dysbiosis generally observed in metabolic or infectious inflammatory diseases of the lower gastrointestinal tract. PMID:27147260

  20. Development of the preterm infant gut microbiome: A research priority

    DOE PAGES

    Groer, Maureen W.; Luciano, Angel A.; Dishaw, Larry J.; Ashmeade, Terri L.; Miller, Elizabeth; Gilbert, Jack A.

    2014-10-13

    The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiome due to multiple factors, including physiological immaturity and prenatal/postnatal influences that disrupt the development of a normal gut flora. However, little is known about the developmental succession of the microbiota in preterm infants as they grow and mature. This review provides a synthesis of our understanding of the normal development of the infant gut microbiome and contrasts this with dysbiotic development in the VLBW infant. The role of human milk in normal gut microbial development is emphasized, along with the role ofmore » the gut microbiome in immune development and gastroenteric health. Current research provides evidence that the gut microbiome interacts extensively with many physiological systems and metabolic processes in the developing infant. However, to the best of our knowledge, there are currently no studies prospectively mapping the gut microbiome of VLBW infants through early childhood. This knowledge gap must be filled to inform a healthcare system that can provide for the growth, health, and development of VLBW infants. In conclusion, the study speculates about how the VLBW infants’ gut microbiome might function through host-microbe interactions to contribute to the sequelae of preterm birth, including its influence on growth, development, and general health of the infant host.« less

  1. Development of the preterm infant gut microbiome: A research priority

    SciTech Connect

    Groer, Maureen W.; Luciano, Angel A.; Dishaw, Larry J.; Ashmeade, Terri L.; Miller, Elizabeth; Gilbert, Jack A.

    2014-10-13

    The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiome due to multiple factors, including physiological immaturity and prenatal/postnatal influences that disrupt the development of a normal gut flora. However, little is known about the developmental succession of the microbiota in preterm infants as they grow and mature. This review provides a synthesis of our understanding of the normal development of the infant gut microbiome and contrasts this with dysbiotic development in the VLBW infant. The role of human milk in normal gut microbial development is emphasized, along with the role of the gut microbiome in immune development and gastroenteric health. Current research provides evidence that the gut microbiome interacts extensively with many physiological systems and metabolic processes in the developing infant. However, to the best of our knowledge, there are currently no studies prospectively mapping the gut microbiome of VLBW infants through early childhood. This knowledge gap must be filled to inform a healthcare system that can provide for the growth, health, and development of VLBW infants. In conclusion, the study speculates about how the VLBW infants’ gut microbiome might function through host-microbe interactions to contribute to the sequelae of preterm birth, including its influence on growth, development, and general health of the infant host.

  2. Development of the preterm infant gut microbiome: a research priority

    PubMed Central

    2014-01-01

    The very low birth weight (VLBW) infant is at great risk for marked dysbiosis of the gut microbiome due to multiple factors, including physiological immaturity and prenatal/postnatal influences that disrupt the development of a normal gut flora. However, little is known about the developmental succession of the microbiota in preterm infants as they grow and mature. This review provides a synthesis of our understanding of the normal development of the infant gut microbiome and contrasts this with dysbiotic development in the VLBW infant. The role of human milk in normal gut microbial development is emphasized, along with the role of the gut microbiome in immune development and gastroenteric health. Current research provides evidence that the gut microbiome interacts extensively with many physiological systems and metabolic processes in the developing infant. However, to the best of our knowledge, there are currently no studies prospectively mapping the gut microbiome of VLBW infants through early childhood. This knowledge gap must be filled to inform a healthcare system that can provide for the growth, health, and development of VLBW infants. The paper concludes with speculation about how the VLBW infants’ gut microbiome might function through host-microbe interactions to contribute to the sequelae of preterm birth, including its influence on growth, development, and general health of the infant host. PMID:25332768

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

    PubMed Central

    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

  4. Systematic genomic analysis reveals the complementary aerobic and anaerobic respiration capacities of the human gut microbiota.

    PubMed

    Ravcheev, Dmitry A; Thiele, Ines

    2014-01-01

    Because of the specific anatomical and physiological properties of the human intestine, a specific oxygen gradient builds up within this organ that influences the intestinal microbiota. The intestinal microbiome has been intensively studied in recent years, and certain respiratory substrates used by gut inhabiting microbes have been shown to play a crucial role in human health. Unfortunately, a systematic analysis has not been previously performed to determine the respiratory capabilities of human gut microbes (HGM). Here, we analyzed the distribution of aerobic and anaerobic respiratory reductases in 254 HGM genomes. In addition to the annotation of known enzymes, we also predicted a novel microaerobic reductase and novel thiosulfate reductase. Based on this comprehensive assessment of respiratory reductases in the HGM, we proposed a number of exchange pathways among different bacteria involved in the reduction of various nitrogen oxides. The results significantly expanded our knowledge of HGM metabolism and interactions in bacterial communities.

  5. Systematic genomic analysis reveals the complementary aerobic and anaerobic respiration capacities of the human gut microbiota.

    PubMed

    Ravcheev, Dmitry A; Thiele, Ines

    2014-01-01

    Because of the specific anatomical and physiological properties of the human intestine, a specific oxygen gradient builds up within this organ that influences the intestinal microbiota. The intestinal microbiome has been intensively studied in recent years, and certain respiratory substrates used by gut inhabiting microbes have been shown to play a crucial role in human health. Unfortunately, a systematic analysis has not been previously performed to determine the respiratory capabilities of human gut microbes (HGM). Here, we analyzed the distribution of aerobic and anaerobic respiratory reductases in 254 HGM genomes. In addition to the annotation of known enzymes, we also predicted a novel microaerobic reductase and novel thiosulfate reductase. Based on this comprehensive assessment of respiratory reductases in the HGM, we proposed a number of exchange pathways among different bacteria involved in the reduction of various nitrogen oxides. The results significantly expanded our knowledge of HGM metabolism and interactions in bacterial communities. PMID:25538694

  6. Gut Microbiota Diversity and Human Diseases: Should We Reintroduce Key Predators in Our Ecosystem?

    PubMed Central

    Mosca, Alexis; Leclerc, Marion; Hugot, Jean P.

    2016-01-01

    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. PMID:27065999

  7. Novel {alpha}-glucosidase from human gut microbiome : substrate specificities and their switch.

    SciTech Connect

    Tan, K.; Tesar, C.; Wilton, R.; Keigher, L.; Babnigg, G.; Joachimiak, A.; Biosciences Division

    2010-01-01

    The human intestine harbors a large number of microbes forming a complex microbial community that greatly affects the physiology and pathology of the host. In the human gut microbiome, the enrichment in certain protein gene families appears to be widespread. They include enzymes involved in carbohydrate metabolism such as glucoside hydrolases of dietary polysaccharides and glycoconjugates. We report the crystal structures (wild type, 2 mutants, and a mutant/substrate complex) and the enzymatic activity of a recombinant {alpha}-glucosidase from human gut bacterium Ruminococcus obeum. The first ever protein structures from this bacterium reveal a structural homologue to human intestinal maltase-glucoamylase with a highly conserved catalytic domain and reduced auxiliary domains. The {alpha}-glucosidase, a member of GH31 family, shows substrate preference for {alpha}(1-6) over {alpha}(1-4) glycosidic linkages and produces glucose from isomaltose as well as maltose. The preference can be switched by a single mutation at its active site, suggestive of widespread adaptation to utilization of a variety of polysaccharides by intestinal micro-organisms as energy resources. Novel {alpha}-glucosidase from human gut microbiome: substrate specificities and their switch.

  8. Obesity and the gut microbiome: pathophysiological aspects.

    PubMed

    Bradlow, H Leon

    2014-01-01

    While there is a large volume of literature describing a role for obesity as a risk factor for breast cancer and many other cancers, in the main a causal relationship has not been established. If the study is limited to breast cancer risk, it has been suggested that the increase in sex steroid formation that occurs in postmenopausal women plays a role. Obesity is known to be associated with chronic low grade inflammation, but no reason for this association has been offered in the past. The gut microbiome, while known to be enormous, has not in the past been considered as a metabolic role player in the body. This is now recognized to be the case. Recent studies have found the obesity is correlated with an alteration in the gut microbiome. In obese individual there is a change in the relative proportions of the two major classes of bacteria - bacteroides and firmacutes - with the latter dominant in obesity and resulting in the formation of increased amounts of metabolic endotoxins like deoxycholic acid and lipopolysaccharides (LPS). Obese individuals show a decrease in the concentration of Akkermansia muciniphila in the mucus that lines the intestinal wall, resulting in thinner mucus and a weakened intestinal lining and permitting metabolic endotoxins formed by other bacterial flora like LPS to enter the blood steam and cause the chronic inflammation associated with obesity. The change in the microbiome profile results in increases in bacterial strains that are more efficient at generating energy, leading to increased obesity. In mice, it has been shown that introducing gut bacterial flora from the cecum of obese mice into germ-free mice results in increased obesity with lesser food consumption while the reverse, introducing bacterial flora from lean mice results in a loss in weight. This raises the attractive possibility that manipulating the gut microbiome could facilitate weight loss or prevent obesity in humans.

  9. The abundance of antibiotic resistance genes in human guts has correlation to the consumption of antibiotics in animal.

    PubMed

    Hu, Yongfei; Yang, Xi; Lu, Na; Zhu, Baoli

    2014-01-01

    Increasing evidence has accumulated to support that the human gut is a reservoir for antibiotic resistance genes. We previously identified more than 1000 genes displaying high similarity with known antibiotic resistance genes in the human gut gene set generated from the Chinese, Danish, and Spanish populations. Here, first, we add our new understanding of antibiotic resistance genes in the US and the Japanese populations; next, we describe the structure of a vancomycin-resistant operon in a Danish sample; and finally, we provide discussions on the correlation of the abundance of resistance genes in human gut with the antibiotic consumption in human medicine and in animal husbandry. These results, combined with those we published previously, provide comprehensive insights into the antibiotic resistance genes in the human gut microbiota at a population level.

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

    PubMed

    Jacobsen, Ulrik Plesner; Nielsen, Henrik Bjørn; Hildebrand, Falk; Raes, Jeroen; Sicheritz-Ponten, Thomas; Kouskoumvekaki, Irene; Panagiotou, Gianni

    2013-04-01

    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 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 microbiome based solely on metagenomics sequencing data derived from fecal samples of 124 Europeans (healthy, obese and with inflammatory bowel disease). Interestingly, three distinct clusters of individuals with high, medium and low metabolic potential were observed. By illustrating these results in the context of bacterial population, we concluded that the abundance of the Prevotella genera is a key factor indicating a low metabolic potential. These metagenome-based metabolic signatures were used to study the interaction networks between bacteria-specific metabolites and human proteins. We found that thirty-three such metabolites interact with disease-relevant protein complexes several of which are highly expressed in cells and tissues involved in the signaling and shaping of the adaptive immune system and associated with squamous cell carcinoma and bladder cancer. From this set of metabolites, eighteen are present in DrugBank providing evidence that we carry a natural 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.

  11. Impact of dietary resistant starch type 4 on human gut microbiota and immunometabolic functions.

    PubMed

    Upadhyaya, Bijaya; McCormack, Lacey; Fardin-Kia, Ali Reza; Juenemann, Robert; Nichenametla, Sailendra; Clapper, Jeffrey; Specker, Bonny; Dey, Moul

    2016-01-01

    Dietary modulation of the gut microbiota impacts human health. Here we investigated the hitherto unknown effects of resistant starch type 4 (RS4) enriched diet on gut microbiota composition and short-chain fatty acid (SCFA) concentrations in parallel with host immunometabolic functions in twenty individuals with signs of metabolic syndrome (MetS). Cholesterols, fasting glucose, glycosylated haemoglobin, and proinflammatory markers in the blood as well as waist circumference and % body fat were lower post intervention in the RS4 group compared with the control group. 16S-rRNA gene sequencing revealed a differential abundance of 71 bacterial operational taxonomic units, including the enrichment of three Bacteroides species and one each of Parabacteroides, Oscillospira, Blautia, Ruminococcus, Eubacterium, and Christensenella species in the RS4 group. Gas chromatography-mass spectrometry revealed higher faecal SCFAs, including butyrate, propionate, valerate, isovalerate, and hexanoate after RS4-intake. Bivariate analyses showed RS4-specific associations of the gut microbiota with the host metabolic functions and SCFA levels. Here we show that dietary RS4 induced changes in the gut microbiota are linked to its biological activity in individuals with signs of MetS. These findings have potential implications for dietary guidelines in metabolic health management. PMID:27356770

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

    PubMed

    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. PMID:27507964

  13. Dissecting the in Vivo Metabolic Potential of Two Human Gut Acetogens*

    PubMed Central

    Rey, Federico E.; Faith, Jeremiah J.; Bain, James; Muehlbauer, Michael J.; Stevens, Robert D.; Newgard, Christopher B.; Gordon, Jeffrey I.

    2010-01-01

    Fermenting microbial communities generate hydrogen; its removal through the production of acetate, methane, or hydrogen sulfide modulates the efficiency of energy extraction from available nutrients in many ecosystems. We noted that pathway components for acetogenesis are more abundantly and consistently represented in the gut microbiomes of monozygotic twins and their mothers than components for methanogenesis or sulfate reduction and subsequently analyzed the metabolic potential of two sequenced human gut acetogens, Blautia hydrogenotrophica and Marvinbryantia formatexigens in vitro and in the intestines of gnotobiotic mice harboring a prominent saccharolytic bacterium. To do so, we developed a generally applicable method for multiplex sequencing of expressed microbial mRNAs (microbial RNA-Seq) and, together with mass spectrometry of metabolites, showed that these organisms have distinct patterns of substrate utilization. B. hydrogenotrophica targets aliphatic and aromatic amino acids. It increases the efficiency of fermentation by consuming reducing equivalents, thereby maintaining a high NAD+/NADH ratio and boosting acetate production. In contrast, M. formatexigens consumes oligosaccharides, does not impact the redox state of the gut, and boosts the yield of succinate. These findings have strategic implications for those who wish to manipulate the hydrogen economy of gut microbial communities in ways that modulate energy harvest. PMID:20444704

  14. Dissecting the in vivo metabolic potential of two human gut acetogens.

    PubMed

    Rey, Federico E; Faith, Jeremiah J; Bain, James; Muehlbauer, Michael J; Stevens, Robert D; Newgard, Christopher B; Gordon, Jeffrey I

    2010-07-16

    Fermenting microbial communities generate hydrogen; its removal through the production of acetate, methane, or hydrogen sulfide modulates the efficiency of energy extraction from available nutrients in many ecosystems. We noted that pathway components for acetogenesis are more abundantly and consistently represented in the gut microbiomes of monozygotic twins and their mothers than components for methanogenesis or sulfate reduction and subsequently analyzed the metabolic potential of two sequenced human gut acetogens, Blautia hydrogenotrophica and Marvinbryantia formatexigens in vitro and in the intestines of gnotobiotic mice harboring a prominent saccharolytic bacterium. To do so, we developed a generally applicable method for multiplex sequencing of expressed microbial mRNAs (microbial RNA-Seq) and, together with mass spectrometry of metabolites, showed that these organisms have distinct patterns of substrate utilization. B. hydrogenotrophica targets aliphatic and aromatic amino acids. It increases the efficiency of fermentation by consuming reducing equivalents, thereby maintaining a high NAD(+)/NADH ratio and boosting acetate production. In contrast, M. formatexigens consumes oligosaccharides, does not impact the redox state of the gut, and boosts the yield of succinate. These findings have strategic implications for those who wish to manipulate the hydrogen economy of gut microbial communities in ways that modulate energy harvest.

  15. Impact of dietary resistant starch type 4 on human gut microbiota and immunometabolic functions

    PubMed Central

    Upadhyaya, Bijaya; McCormack, Lacey; Fardin-Kia, Ali Reza; Juenemann, Robert; Nichenametla, Sailendra; Clapper, Jeffrey; Specker, Bonny; Dey, Moul

    2016-01-01

    Dietary modulation of the gut microbiota impacts human health. Here we investigated the hitherto unknown effects of resistant starch type 4 (RS4) enriched diet on gut microbiota composition and short-chain fatty acid (SCFA) concentrations in parallel with host immunometabolic functions in twenty individuals with signs of metabolic syndrome (MetS). Cholesterols, fasting glucose, glycosylated haemoglobin, and proinflammatory markers in the blood as well as waist circumference and % body fat were lower post intervention in the RS4 group compared with the control group. 16S-rRNA gene sequencing revealed a differential abundance of 71 bacterial operational taxonomic units, including the enrichment of three Bacteroides species and one each of Parabacteroides, Oscillospira, Blautia, Ruminococcus, Eubacterium, and Christensenella species in the RS4 group. Gas chromatography–mass spectrometry revealed higher faecal SCFAs, including butyrate, propionate, valerate, isovalerate, and hexanoate after RS4-intake. Bivariate analyses showed RS4-specific associations of the gut microbiota with the host metabolic functions and SCFA levels. Here we show that dietary RS4 induced changes in the gut microbiota are linked to its biological activity in individuals with signs of MetS. These findings have potential implications for dietary guidelines in metabolic health management. PMID:27356770

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

    PubMed Central

    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. PMID:27507964

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

    PubMed

    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

    2012-01-01

    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.

  18. Direct Analysis of Genes Encoding 16S rRNA from Complex Communities Reveals Many Novel Molecular Species within the Human Gut

    PubMed Central

    Suau, Antonia; Bonnet, Régis; Sutren, Malène; Godon, Jean-Jacques; Gibson, Glenn R.; Collins, Matthew D.; Doré, Joel

    1999-01-01

    The human intestinal tract harbors a complex microbial ecosystem which plays a key role in nutrition and health. Although this microbiota has been studied in great detail by culture techniques, microscopic counts on human feces suggest that 60 to 80% of the observable bacteria cannot be cultivated. Using comparative analysis of cloned 16S rRNA gene (rDNA) sequences, we have investigated the bacterial diversity (both cultivated and noncultivated bacteria) within an adult-male fecal sample. The 284 clones obtained from 10-cycle PCR were classified into 82 molecular species (at least 98% similarity). Three phylogenetic groups contained 95% of the clones: the Bacteroides group, the Clostridium coccoides group, and the Clostridium leptum subgroup. The remaining clones were distributed among a variety of phylogenetic clusters. Only 24% of the molecular species recovered corresponded to described organisms (those whose sequences were available in public databases), and all of these were established members of the dominant human fecal flora (e.g., Bacteroides thetaiotaomicron, Fusobacterium prausnitzii, and Eubacterium rectale). However, the majority of generated rDNA sequences (76%) did not correspond to known organisms and clearly derived from hitherto unknown species within this human gut microflora. PMID:10543789

  19. Biotransformation of aesculin by human gut bacteria and identification of its metabolites in rat urine

    PubMed Central

    Ding, Wei-Jun; Deng, Yun; Feng, Hao; Liu, Wei-Wei; Hu, Rong; Li, Xiang; Gu, Zhe-Ming; Dong, Xiao-Ping

    2009-01-01

    AIM: To observe the biotransformation process of a Chinese compound, aesculin, by human gut bacteria, and to identify its metabolites in rat urine. METHODS: Representative human gut bacteria were collected from 20 healthy volunteers, and then utilized in vitro to biotransform aesculin under anaerobic conditions. At 0, 2, 4, 8, 12, 16, 24, 48 and 72 h post-incubation, 10 mL of culture medium was collected. Metabolites of aesculin were extracted 3 × from rat urine with methanol and analyzed by HPLC. For in vivo metabolite analysis, aesculetin (100 mg/kg) was administered to rats via stomach gavage, rat urine was collected from 6 to 48 h post-administration, and metabolite analysis was performed by LC/ESI-MS and MS/MS in the positive and negative modes. RESULTS: Human gut bacteria could completely convert aesculin into aesculetin in vitro. The biotransformation process occurred from 8 to 24 h post-incubation, with its highest activity was seen from 8 to 12 h. The in vitro process was much slower than the in vivo process. In contrast to the in vitro model, six aesculetin metabolites were identified in rat urine, including 6-hydroxy-7-gluco-coumarin (M1), 6-hydroxy-7-sulf-coumarin (M2), 6, 7-di-gluco-coumarin (M3), 6-glc-7-gluco-coumarin (M4), 6-O-methyl-7-gluco-coumarin (M5) and 6-O-methyl-7-sulf-coumarin (M6). Of which, M2 and M6 were novel metabolites. CONCLUSION: Aesculin can be transferred into aesculetin by human gut bacteria and is further modified by the host in vivo. The diverse metabolites of aesculin may explain its pleiotropic pharmaceutical effects. PMID:19322928

  20. Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance.

    PubMed

    Saad, M J A; Santos, A; Prada, P O

    2016-07-01

    Obesity and insulin resistance are the major predisposing factors to comorbidities, such as Type 2 diabetes, nonalcoholic fatty liver disease, cardiovascular and neurodegenerative diseases, and several types of cancer. The prevalence of obesity is still increasing worldwide and now affects a large number of individuals. Here, we review the role of the gut microbiota in the pathophysiology of insulin resistance/obesity. The human intestine is colonized by ∼100 trillion bacteria, which constitute the gut microbiota. Studies have shown that lean and overweight rodents and humans may present differences in the composition of their intestinal flora. Over the past 10 years, data from different sources have established a causal link between the intestinal microbiota and obesity/insulin resistance. It is important to emphasize that diet-induced obesity promotes insulin resistance by mechanisms independent and dependent on gut microbiota. In this review, we present several mechanisms that contribute to explaining the link between intestinal flora and insulin resistance/obesity. The LPS from intestinal flora bacteria can induce a chronic subclinical inflammatory process and obesity, leading to insulin resistance through activation of TLR4. The reduction in circulating SCFA may also have an essential role in the installation of reduced insulin sensitivity and obesity. Other mechanisms include effects of bile acids, branched-chain amino acids (BCAA), and some other lesser-known factors. In the near future, this area should open new therapeutic avenues for obesity/insulin resistance and its comorbidities. PMID:27252163

  1. Metagenomic Analysis of the Human Distal Gut Microbiome

    PubMed Central

    Gill, Steven R.; Pop, Mihai; DeBoy, Robert T.; Eckburg, Paul B.; Turnbaugh, Peter J.; Samuel, Buck S.; Gordon, Jeffrey I.; Relman, David A.; Fraser-Liggett, Claire M.; Nelson, Karen E.

    2011-01-01

    The human intestinal microbiota is composed of 1013 to 1014 microorganisms whose collective genome (“microbiome”) contains at least 100 times as many genes as our own genome. We analyzed ~78 million base pairs of unique DNA sequence and 2062 polymerase chain reaction–amplified 16S ribosomal DNA sequences obtained from the fecal DNAs of two healthy adults. Using metabolic function analyses of identified genes, we compared our human genome with the average content of previously sequenced microbial genomes. Our microbiome has significantly enriched metabolism of glycans, amino acids, and xenobiotics; methanogenesis; and 2-methyl-d-erythritol 4-phosphate pathway–mediated biosynthesis of vitamins and isoprenoids. Thus, humans are superorganisms whose metabolism represents an amalgamation of microbial and human attributes. PMID:16741115

  2. Archaea and the human gut: New beginning of an old story

    PubMed Central

    Gaci, Nadia; Borrel, Guillaume; Tottey, William; O’Toole, Paul William; Brugère, Jean-François

    2014-01-01

    Methanogenic archaea are known as human gut inhabitants since more than 30 years ago through the detection of methane in the breath and isolation of two methanogenic species belonging to the order Methanobacteriales, Methanobrevibacter smithii and Methanosphaera stadtmanae. During the last decade, diversity of archaea encountered in the human gastrointestinal tract (GIT) has been extended by sequence identification and culturing of new strains. Here we provide an updated census of the archaeal diversity associated with the human GIT and their possible role in the gut physiology and health. We particularly focus on the still poorly characterized 7th order of methanogens, the Methanomassiliicoccales, associated to aged population. While also largely distributed in non-GIT environments, our actual knowledge on this novel order of methanogens has been mainly revealed through GIT inhabitants. They enlarge the number of final electron acceptors of the gut metabolites to mono- di- and trimethylamine. Trimethylamine is exclusively a microbiota-derived product of nutrients (lecithin, choline, TMAO, L-carnitine) from normal diet, from which seems originate two diseases, trimethylaminuria (or Fish-Odor Syndrome) and cardiovascular disease through the proatherogenic property of its oxidized liver-derived form. This therefore supports interest on these methanogenic species and its use as archaebiotics, a term coined from the notion of archaea-derived probiotics. PMID:25473158

  3. Genome signature-based dissection of human gut metagenomes to extract subliminal viral sequences

    PubMed Central

    Ogilvie, Lesley A.; Bowler, Lucas D.; Caplin, Jonathan; Dedi, Cinzia; Diston, David; Cheek, Elizabeth; Taylor, Huw; Ebdon, James E.; Jones, Brian V.

    2013-01-01

    Bacterial viruses (bacteriophages) have a key role in shaping the development and functional outputs of host microbiomes. Although metagenomic approaches have greatly expanded our understanding of the prokaryotic virosphere, additional tools are required for the phage-oriented dissection of metagenomic data sets, and host-range affiliation of recovered sequences. Here we demonstrate the application of a genome signature-based approach to interrogate conventional whole-community metagenomes and access subliminal, phylogenetically targeted, phage sequences present within. We describe a portion of the biological dark matter extant in the human gut virome, and bring to light a population of potentially gut-specific Bacteroidales-like phage, poorly represented in existing virus like particle-derived viral metagenomes. These predominantly temperate phage were shown to encode functions of direct relevance to human health in the form of antibiotic resistance genes, and provided evidence for the existence of putative ‘viral-enterotypes’ among this fraction of the human gut virome. PMID:24036533

  4. Glycoantigens Induce Human Peripheral Tr1 Cell Differentiation with Gut-homing Specialization*

    PubMed Central

    Kreisman, Lori S. C.; Cobb, Brian A.

    2011-01-01

    The carbohydrate antigen (glycoantigen) PSA from an intestinal commensal bacteria is able to down-regulate inflammatory bowel disease in model mice, suggesting that stimulation with PSA results in regulatory T cell (Treg) generation. However, mechanisms of how peripheral human T cells respond and home in response to commensal antigens are still not understood. Here, we demonstrate that a single exposure to PSA induces differentiation of human peripheral CD4+ T cells into type-Tr1 Tregs. This is in contrast to mouse models where PSA induced the production of Foxp3+ iTregs. The human PSA-induced Tr1 cells are profoundly anergic and exhibit nonspecific bystander suppression mediated by IL-10 secretion. Most surprisingly, glycoantigen exposure provoked expression of gut homing receptors on their surface. These findings reveal a mechanism for immune homeostasis in the gut whereby exposure to commensal glycoantigens provides the requisite information to responding T cells for proper tissue localization (gut) and function (anti-inflammatory/regulatory). PMID:21228275

  5. Molecular details of a starch utilization pathway in the human gut symbiont Eubacterium rectale

    PubMed Central

    Cockburn, Darrell W.; Orlovsky, Nicole I.; Foley, Matthew H.; Kwiatkowski, Kurt J.; Bahr, Constance M.; Maynard, Mallory; Demeler, Borries; Koropatkin, Nicole M.

    2015-01-01

    Summary Eubacterium rectale is a prominent human gut symbiont yet little is known about the molecular strategies this bacterium has developed to acquire nutrients within the competitive gut ecosystem. Starch is one of the most abundant glycans in the human diet, and E. rectale increases in vivo when the host consumes a diet rich in resistant starch, although it is not a primary degrader of this glycan. Here we present the results of a quantitative proteomics study in which we identify two glycoside hydrolase 13 family enzymes, and three ABC transporter solute-binding proteins that are abundant during growth on starch and, we hypothesize, work together at the cell surface to degrade starch and capture the released maltooligosaccharides. EUR_21100 is a multidomain cell wall anchored amylase that preferentially targets starch polysaccharides, liberating maltotetraose, while the membrane associated maltogenic amylase EUR_01860 breaks down maltooligosaccharides longer than maltotriose. The three solute-binding proteins display a range of glycan-binding specificities that ensure the capture of glucose through maltoheptaose and some α1,6-branched glycans. Taken together, we describe a pathway for starch utilization by E. rectale DSM 17629 that may be conserved among other starch-degrading Clostridium cluster XIVa organisms in the human gut. PMID:25388295

  6. A novel transcriptional regulator of L-arabinose utilization in human gut bacteria

    PubMed Central

    Chang, Changsoo; Tesar, Christine; Li, Xiaoqing; Kim, Youngchang; Rodionov, Dmitry A.; Joachimiak, Andrzej

    2015-01-01

    Carbohydrate metabolism plays a crucial role in the ecophysiology of human gut microbiota. Mechanisms of transcriptional regulation of sugar catabolism in commensal and prevalent human gut bacteria such as Bacteroides thetaiotaomicron remain mostly unknown. By a combination of bioinformatics and experimental approaches, we have identified an NrtR family transcription factor (BT0354 in B. thetaiotaomicron, BtAraR) as a novel regulator controlling the arabinose utilization genes. L-arabinose was confirmed to be a negative effector of BtAraR. We have solved the crystal structures of the apo and L-arabinose-bound BtAraR proteins, as well as the complex of apo-protein with a specific DNA operator. BtAraR forms a homodimer with each subunit comprised of the ligand-binding Nudix hydrolase-like domain and the DNA-binding winged-helix-turn-helix (wHTH) domain. We have identified the residues involved in binding of L-arabinose and recognition of DNA. The majority of these residues are well conserved in the AraR orthologs in Bacteroidetes. In the structure of the BtAraR–DNA complex, we found the unique interaction of arginine intercalating its guanidinum moiety into the base pair stacking of B-DNA. L-arabinose binding induces movement of wHTH domains, resulting in a conformation unsuitable for DNA binding. Our analysis facilitates reconstruction of the metabolic and regulatory networks involved in carbohydrate utilization in human gut Bacteroides. PMID:26438537

  7. Archaea and the human gut: new beginning of an old story.

    PubMed

    Gaci, Nadia; Borrel, Guillaume; Tottey, William; O'Toole, Paul William; Brugère, Jean-François

    2014-11-21

    Methanogenic archaea are known as human gut inhabitants since more than 30 years ago through the detection of methane in the breath and isolation of two methanogenic species belonging to the order Methanobacteriales, Methanobrevibacter smithii and Methanosphaera stadtmanae. During the last decade, diversity of archaea encountered in the human gastrointestinal tract (GIT) has been extended by sequence identification and culturing of new strains. Here we provide an updated census of the archaeal diversity associated with the human GIT and their possible role in the gut physiology and health. We particularly focus on the still poorly characterized 7th order of methanogens, the Methanomassiliicoccales, associated to aged population. While also largely distributed in non-GIT environments, our actual knowledge on this novel order of methanogens has been mainly revealed through GIT inhabitants. They enlarge the number of final electron acceptors of the gut metabolites to mono- di- and trimethylamine. Trimethylamine is exclusively a microbiota-derived product of nutrients (lecithin, choline, TMAO, L-carnitine) from normal diet, from which seems originate two diseases, trimethylaminuria (or Fish-Odor Syndrome) and cardiovascular disease through the proatherogenic property of its oxidized liver-derived form. This therefore supports interest on these methanogenic species and its use as archaebiotics, a term coined from the notion of archaea-derived probiotics. PMID:25473158

  8. A novel transcriptional regulator of L-arabinose utilization in human gut bacteria.

    PubMed

    Chang, Changsoo; Tesar, Christine; Li, Xiaoqing; Kim, Youngchang; Rodionov, Dmitry A; Joachimiak, Andrzej

    2015-12-01

    Carbohydrate metabolism plays a crucial role in the ecophysiology of human gut microbiota. Mechanisms of transcriptional regulation of sugar catabolism in commensal and prevalent human gut bacteria such as Bacteroides thetaiotaomicron remain mostly unknown. By a combination of bioinformatics and experimental approaches, we have identified an NrtR family transcription factor (BT0354 in B. thetaiotaomicron, BtAraR) as a novel regulator controlling the arabinose utilization genes. L-arabinose was confirmed to be a negative effector of BtAraR. We have solved the crystal structures of the apo and L-arabinose-bound BtAraR proteins, as well as the complex of apo-protein with a specific DNA operator. BtAraR forms a homodimer with each subunit comprised of the ligand-binding Nudix hydrolase-like domain and the DNA-binding winged-helix-turn-helix (wHTH) domain. We have identified the residues involved in binding of L-arabinose and recognition of DNA. The majority of these residues are well conserved in the AraR orthologs in Bacteroidetes. In the structure of the BtAraR-DNA complex, we found the unique interaction of arginine intercalating its guanidinum moiety into the base pair stacking of B-DNA. L-arabinose binding induces movement of wHTH domains, resulting in a conformation unsuitable for DNA binding. Our analysis facilitates reconstruction of the metabolic and regulatory networks involved in carbohydrate utilization in human gut Bacteroides.

  9. Development of an Enhanced Metaproteomic Approach for Deepening the Microbiome Characterization of the Human Infant Gut

    DOE PAGES

    Xiong, Weili; Richard J. Giannone; Morowitz, Michael J.; Banfield, Jillian F.; Robert L. Hettich

    2014-10-28

    The early-life microbiota establishment in the human infant gut is highly variable and plays a crucial role in host nutrients and immunity maturation. While high-performance mass spectrometry (MS)-based metaproteomics is a powerful method for the functional characterization of complex microbial communities, the construction of comprehensive metaproteomic information in human fecal samples is inhibited by the presence of abundant human proteins. To alleviate this restriction, we have designed a novel metaproteomic strategy based on Double Filtering (DF) to enhance microbial protein characterization in complex fecal samples from healthy premature infants. We improved the overall depth of infant gut proteome measurement, withmore » an increase in the number of identified low abundance proteins, and observed greater than twofold improvement in metrics for microbial protein identifications and quantifications with a relatively high rank correlation to control. We further showed the substantial enhancement of this approach for extensively interpreting microbial functional categories between infants by affording more detailed and confident identified categories. This approach provided an avenue for in-depth measurement in the microbial component of infant fecal samples and thus comprehensive characterization of infant gut microbiome functionality.« less

  10. Development of an Enhanced Metaproteomic Approach for Deepening the Microbiome Characterization of the Human Infant Gut

    SciTech Connect

    Xiong, Weili; Richard J. Giannone; Morowitz, Michael J.; Banfield, Jillian F.; Robert L. Hettich

    2014-10-28

    The early-life microbiota establishment in the human infant gut is highly variable and plays a crucial role in host nutrients and immunity maturation. While high-performance mass spectrometry (MS)-based metaproteomics is a powerful method for the functional characterization of complex microbial communities, the construction of comprehensive metaproteomic information in human fecal samples is inhibited by the presence of abundant human proteins. To alleviate this restriction, we have designed a novel metaproteomic strategy based on Double Filtering (DF) to enhance microbial protein characterization in complex fecal samples from healthy premature infants. We improved the overall depth of infant gut proteome measurement, with an increase in the number of identified low abundance proteins, and observed greater than twofold improvement in metrics for microbial protein identifications and quantifications with a relatively high rank correlation to control. We further showed the substantial enhancement of this approach for extensively interpreting microbial functional categories between infants by affording more detailed and confident identified categories. This approach provided an avenue for in-depth measurement in the microbial component of infant fecal samples and thus comprehensive characterization of infant gut microbiome functionality.

  11. The human gut microbiome: a review of the effect of obesity and surgically induced weight loss.

    PubMed

    Sweeney, Timothy E; Morton, John M

    2013-06-01

    Recent advances in parallel genomic processing and computational mapping have been applied to the native human microbial environment to provide a new understanding of the role of the microbiome in health and disease. In particular, studies of the distal gut microbiome have proposed that changes in gut microbiota are related to obesity, the metabolic syndrome, and Western diet. We examined the changes in the distal gut microbiome composition as it relates to the lean and obese phenotypes, particularly after surgical weight loss. A PubMed search of publications from January 1, 2005, through December 31, 2012, used the search terms weight, obesity, microbiome, and bariatric surgery. We included studies that provided information on subjects' weight and/or body mass index and a formal assessment of the microbiome. Certain bacteria, specifically the archaeon Methanobrevibacter smithii, have enhanced ability to metabolize dietary substrate, thereby increasing host energy intake and weight gain. With weight loss, there is a decrease in the ratio of Firmicutes to Bacteroidetes phyla. One major finding from microbial sequencing analyses after Roux-en-Y gastric bypass is the comparative overabundance of Proteobacteria in the distal gut microbiome, which is distinct from the changes seen in weight loss without Roux-en-Y gastric bypass. This review provides the practicing surgeon with (1) an update on the state of a rapidly innovating branch of clinical bioinformatics, specifically, the microbiome; (2) a new understanding of the microbiome changes after Roux-en-Y gastric bypass and weight loss; and (3) a basis for understanding further clinical applications of studies of the distal gut microbiome, such as in Crohn disease, ulcerative colitis, and infectious colitis.

  12. Members of the human gut microbiota involved in recovery from Vibrio cholerae infection

    PubMed Central

    Hsiao, Ansel; Shamsir Ahmed, A.M.; Subramanian, Sathish; Griffin, Nicholas W.; Drewry, Lisa L.; Petri, William A.; Haque, Rashidul; Ahmed, Tahmeed; Gordon, Jeffrey I.

    2015-01-01

    Given the global burden of diarrheal diseases1, it is important to understand how members of the gut microbiota affect the risk for, course of, and recovery from disease in children and adults. The acute, voluminous diarrhea caused by Vibrio cholerae represents a dramatic example of enteropathogen invasion and gut microbial community disruption. We have conducted a detailed time-series metagenomic study of fecal microbiota collected during the acute diarrheal and recovery phases of cholera in a cohort of Bangladeshi adults living in an area with a high burden of disease2. We find that recovery is characterized by a pattern of accumulation of bacterial taxa that shows similarities to the pattern of assembly/maturation of the gut microbiota in healthy Bangladeshi children3. To define underlying mechanisms, we introduced into gnotobiotic mice an artificial community that was composed of human gut bacterial species that directly correlate with recovery from cholera in adults and are indicative of normal microbiota maturation in healthy Bangladeshi children3. One of the species, Ruminococcus obeum, exhibited consistent increases in its relative abundance upon V. cholerae infection of the mice. Follow-up analyses, including mono- and co-colonization studies, established that R. obeum restricts V. cholerae colonization, that R. obeum luxS [autoinducer-2 (AI-2) synthase] expression and AI-2 production increase significantly with V. cholerae invasion, and that R. obeum AI-2 causes quorum-sensing mediated repression of several V. cholerae colonization factors. Co-colonization with V. cholerae mutants disclosed that R. obeum AI-2 reduces Vibrio colonization/pathogenicity through a novel pathway that does not depend on the V. cholerae AI-2 sensor, LuxP. The approach described can be used to mine the gut microbiota of Bangladeshi or other populations for members that use autoinducers and/or other mechanisms to limit colonization with V. cholerae, or conceivably other

  13. Members of the human gut microbiota involved in recovery from Vibrio cholerae infection.

    PubMed

    Hsiao, Ansel; Ahmed, A M Shamsir; Subramanian, Sathish; Griffin, Nicholas W; Drewry, Lisa L; Petri, William A; Haque, Rashidul; Ahmed, Tahmeed; Gordon, Jeffrey I

    2014-11-20

    Given the global burden of diarrhoeal diseases, it is important to understand how members of the gut microbiota affect the risk for, course of, and recovery from disease in children and adults. The acute, voluminous diarrhoea caused by Vibrio cholerae represents a dramatic example of enteropathogen invasion and gut microbial community disruption. Here we conduct a detailed time-series metagenomic study of faecal microbiota collected during the acute diarrhoeal and recovery phases of cholera in a cohort of Bangladeshi adults living in an area with a high burden of disease. We find that recovery is characterized by a pattern of accumulation of bacterial taxa that shows similarities to the pattern of assembly/maturation of the gut microbiota in healthy Bangladeshi children. To define the underlying mechanisms, we introduce into gnotobiotic mice an artificial community composed of human gut bacterial species that directly correlate with recovery from cholera in adults and are indicative of normal microbiota maturation in healthy Bangladeshi children. One of the species, Ruminococcus obeum, exhibits consistent increases in its relative abundance upon V. cholerae infection of the mice. Follow-up analyses, including mono- and co-colonization studies, establish that R. obeum restricts V. cholerae colonization, that R. obeum luxS (autoinducer-2 (AI-2) synthase) expression and AI-2 production increase significantly with V. cholerae invasion, and that R. obeum AI-2 causes quorum-sensing-mediated repression of several V. cholerae colonization factors. Co-colonization with V. cholerae mutants discloses that R. obeum AI-2 reduces Vibrio colonization/pathogenicity through a novel pathway that does not depend on the V. cholerae AI-2 sensor, LuxP. The approach described can be used to mine the gut microbiota of Bangladeshi or other populations for members that use autoinducers and/or other mechanisms to limit colonization with V. cholerae, or conceivably other enteropathogens.

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

    PubMed

    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

    2016-01-01

    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. PMID:27295340

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

    PubMed Central

    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

    2016-01-01

    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. PMID:27295340

  16. Role of the gut microbiota in defining human health

    PubMed Central

    Fujimura, Kei E; Slusher, Nicole A; Cabana, Michael D; Lynch, Susan V

    2010-01-01

    The human superorganism is a conglomerate of mammalian and microbial cells, with the latter estimated to outnumber the former by ten to one and the microbial genetic repertoire (microbiome) to be approximately 100-times greater than that of the human host. Given the ability of the immune response to rapidly counter infectious agents, it is striking that such a large density of microbes can exist in a state of synergy within the human host. This is particularly true of the distal gastrointestinal (GI) tract, which houses up to 1000 distinct bacterial species and an estimated excess of 1 × 1014 microorganisms. An ever-increasing body of evidence implicates the GI microbiota in defining states of health and disease. Here, we review the literature in adult and pediatric GI microbiome studies, the emerging links between microbial community structure, function, infection and disease, and the approaches to manipulate this crucial ecosystem to improve host health. PMID:20377338

  17. Role of the gut microbiota in defining human health.

    PubMed

    Fujimura, Kei E; Slusher, Nicole A; Cabana, Michael D; Lynch, Susan V

    2010-04-01

    The human superorganism is a conglomerate of mammalian and microbial cells, with the latter estimated to outnumber the former by ten to one and the microbial genetic repertoire (microbiome) to be approximately 100-times greater than that of the human host. Given the ability of the immune response to rapidly counter infectious agents, it is striking that such a large density of microbes can exist in a state of synergy within the human host. This is particularly true of the distal gastrointestinal (GI) tract, which houses up to 1000 distinct bacterial species and an estimated excess of 1 x 10(14) microorganisms. An ever-increasing body of evidence implicates the GI microbiota in defining states of health and disease. Here, we review the literature in adult and pediatric GI microbiome studies, the emerging links between microbial community structure, function, infection and disease, and the approaches to manipulate this crucial ecosystem to improve host health.

  18. Fluoroquinolones and qnr genes in sediment, water, soil, and human fecal flora in an environment polluted by manufacturing discharges.

    PubMed

    Rutgersson, Carolin; Fick, Jerker; Marathe, Nachiket; Kristiansson, Erik; Janzon, Anders; Angelin, Martin; Johansson, Anders; Shouche, Yogesh; Flach, Carl-Fredrik; Larsson, D G Joakim

    2014-07-15

    There is increasing concern that environmental antibiotic pollution promotes transfer of resistance genes to the human microbiota. Here, fluoroquinolone-polluted river sediment, well water, irrigated farmland, and human fecal flora of local villagers within a pharmaceutical industrial region in India were analyzed for quinolone resistance (qnr) genes by quantitative PCR. Similar samples from Indian villages farther away from industrial areas, as well as fecal samples from Swedish study participants and river sediment from Sweden, were included for comparison. Fluoroquinolones were detected by MS/MS in well water and soil from all villages located within three km from industrially polluted waterways. Quinolone resistance genes were detected in 42% of well water, 7% of soil samples and in 100% and 18% of Indian and Swedish river sediments, respectively. High antibiotic concentrations in Indian sediment coincided with high abundances of qnr, whereas lower fluoroquinolone levels in well water and soil did not. We could not find support for an enrichment of qnr in fecal samples from people living in the fluoroquinolone-contaminated villages. However, as qnr was detected in 91% of all Indian fecal samples (24% of the Swedish) it suggests that the spread of qnr between people is currently a dominating transmission route.

  19. Ecological Interactions of Bacteria in the Human Gut

    NASA Astrophysics Data System (ADS)

    Falony, Gwen; de Vuyst, Luc

    The colon or large intestine is one of the most important organs of the human body (Macfarlane and Cummings, 1991). Moreover, its inhabitants, the colon microbiota, are the key elements of the human digestive ecosystem. The vast complexity of the human large-intestinal microbiota has inspired researchers to consider it as an organ itself, located inside the colon and acquired postnatally (Bäckhed et al., 2005; Zocco et al., 2007). From a physiologist's point of view, this image of the colon microbiota is relevant: like an organ, it is composed of different cell lineages that communicate with both one another and the host; it consumes, stores, and redistributes energy; it mediates physiologically important chemical transformations; and it is able to maintain and repair itself through self-replication (Bäckhed et al., 2005). As a microbial organ, the human colon community does not only broaden the digestive abilities of the host (Gill et al., 2006), but also influences body processes far beyond digestion (Roberfroid, 2005b; Turnbaugh et al., 2007).

  20. Comparative (Meta)genomic Analysis and Ecological Profiling of Human Gut-Specific Bacteriophage φB124-14

    PubMed Central

    Ogilvie, Lesley A.; Caplin, Jonathan; Dedi, Cinzia; Diston, David; Cheek, Elizabeth; Bowler, Lucas; Taylor, Huw; Ebdon, James; Jones, Brian V.

    2012-01-01

    Bacteriophage associated with the human gut microbiome are likely to have an important impact on community structure and function, and provide a wealth of biotechnological opportunities. Despite this, knowledge of the ecology and composition of bacteriophage in the gut bacterial community remains poor, with few well characterized gut-associated phage genomes currently available. Here we describe the identification and in-depth (meta)genomic, proteomic, and ecological analysis of a human gut-specific bacteriophage (designated φB124-14). In doing so we illuminate a fraction of the biological dark matter extant in this ecosystem and its surrounding eco-genomic landscape, identifying a novel and uncharted bacteriophage gene-space in this community. φB124-14 infects only a subset of closely related gut-associated Bacteroides fragilis strains, and the circular genome encodes functions previously found to be rare in viral genomes and human gut viral metagenome sequences, including those which potentially confer advantages upon phage and/or host bacteria. Comparative genomic analyses revealed φB124-14 is most closely related to φB40-8, the only other publically available Bacteroides sp. phage genome, whilst comparative metagenomic analysis of both phage failed to identify any homologous sequences in 136 non-human gut metagenomic datasets searched, supporting the human gut-specific nature of this phage. Moreover, a potential geographic variation in the carriage of these and related phage was revealed by analysis of their distribution and prevalence within 151 human gut microbiomes and viromes from Europe, America and Japan. Finally, ecological profiling of φB124-14 and φB40-8, using both gene-centric alignment-driven phylogenetic analyses, as well as alignment-free gene-independent approaches was undertaken. This not only verified the human gut-specific nature of both phage, but also indicated that these phage populate a distinct and unexplored ecological landscape

  1. Utilisation of Mucin Glycans by the Human Gut Symbiont Ruminococcus gnavus Is Strain-Dependent

    PubMed Central

    Crost, Emmanuelle H.; Tailford, Louise E.; Le Gall, Gwenaelle; Fons, Michel; Henrissat, Bernard; Juge, Nathalie

    2013-01-01

    Commensal bacteria often have an especially rich source of glycan-degrading enzymes which allow them to utilize undigested carbohydrates from the food or the host. The species Ruminococcus gnavus is present in the digestive tract of ≥90% of humans and has been implicated in gut-related diseases such as inflammatory bowel diseases (IBD). Here we analysed the ability of two R. gnavus human strains, E1 and ATCC 29149, to utilize host glycans. We showed that although both strains could assimilate mucin monosaccharides, only R. gnavus ATCC 29149 was able to grow on mucin as a sole carbon source. Comparative genomic analysis of the two R. gnavus strains highlighted potential clusters and glycoside hydrolases (GHs) responsible for the breakdown and utilization of mucin-derived glycans. Transcriptomic and functional activity assays confirmed the importance of specific GH33 sialidase, and GH29 and GH95 fucosidases in the mucin utilisation pathway. Notably, we uncovered a novel pathway by which R. gnavus ATCC 29149 utilises sialic acid from sialylated substrates. Our results also demonstrated the ability of R. gnavus ATCC 29149 to produce propanol and propionate as the end products of metabolism when grown on mucin and fucosylated glycans. These new findings provide molecular insights into the strain-specificity of R. gnavus adaptation to the gut environment advancing our understanding of the role of gut commensals in health and disease. PMID:24204617

  2. Diversified mcr-1-Harbouring Plasmid Reservoirs Confer Resistance to Colistin in Human Gut Microbiota

    PubMed Central

    Ye, Huiyan; Li, Yihui; Li, Zhencui; Gao, Rongsui; Zhang, Han; Wen, Ronghui; Gao, George F.; Hu, Qinghua

    2016-01-01

    ABSTRACT Colistin is an ultimate line of refuge against multidrug-resistant Gram-negative pathogens. Very recently, the emergence of plasmid-mediated mcr-1 colistin resistance has become a great challenge to global public health, raising the possibility that dissemination of the mcr-1 gene is underestimated and diversified. Here, we report three cases of plasmid-carried MCR-1 colistin resistance in isolates from gut microbiota of diarrhea patients. Structural and functional analyses determined that the colistin resistance is conferred purely by the single mcr-1 gene. Genetic and sequence mapping revealed that mcr-1-harbouring plasmid reservoirs are present in diversity. Together, the data represent the first evidence of diversity in mcr-1-harbouring plasmid reservoirs of human gut microbiota. PMID:27048797

  3. Changes of the human gut microbiome induced by a fermented milk product.

    PubMed

    Veiga, Patrick; Pons, Nicolas; Agrawal, Anurag; Oozeer, Raish; Guyonnet, Denis; Brazeilles, Rémi; Faurie, Jean-Michel; van Hylckama Vlieg, Johan E T; Houghton, Lesley A; Whorwell, Peter J; Ehrlich, S Dusko; Kennedy, Sean P

    2014-01-01

    The gut microbiota (GM) consists of resident commensals and transient microbes conveyed by the diet but little is known about the role of the latter on GM homeostasis. Here we show, by a conjunction of quantitative metagenomics, in silico genome reconstruction and metabolic modeling, that consumption of a fermented milk product containing dairy starters and Bifidobacterium animalis potentiates colonic short chain fatty acids production and decreases abundance of a pathobiont Bilophila wadsworthia compared to a milk product in subjects with irritable bowel syndrome (IBS, n = 28). The GM changes parallel improvement of IBS state, suggesting a role of the fermented milk bacteria in gut homeostasis. Our data challenge the view that microbes ingested with food have little impact on the human GM functioning and rather provide support for beneficial health effects. PMID:25209713

  4. Changes of the human gut microbiome induced by a fermented milk product.

    PubMed

    Veiga, Patrick; Pons, Nicolas; Agrawal, Anurag; Oozeer, Raish; Guyonnet, Denis; Brazeilles, Rémi; Faurie, Jean-Michel; van Hylckama Vlieg, Johan E T; Houghton, Lesley A; Whorwell, Peter J; Ehrlich, S Dusko; Kennedy, Sean P

    2014-01-01

    The gut microbiota (GM) consists of resident commensals and transient microbes conveyed by the diet but little is known about the role of the latter on GM homeostasis. Here we show, by a conjunction of quantitative metagenomics, in silico genome reconstruction and metabolic modeling, that consumption of a fermented milk product containing dairy starters and Bifidobacterium animalis potentiates colonic short chain fatty acids production and decreases abundance of a pathobiont Bilophila wadsworthia compared to a milk product in subjects with irritable bowel syndrome (IBS, n = 28). The GM changes parallel improvement of IBS state, suggesting a role of the fermented milk bacteria in gut homeostasis. Our data challenge the view that microbes ingested with food have little impact on the human GM functioning and rather provide support for beneficial health effects.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27677718

  6. Studying the human gut microbiota in the trans-omics era--focus on metagenomics and metabonomics.

    PubMed

    Tuohy, Kieran M; Gougoulias, Christos; Shen, Qing; Walton, Gemma; Fava, Francesca; Ramnani, Priya

    2009-01-01

    The human gut microbiota comprises a diverse microbial consortium closely co-evolved with the human genome and diet. The importance of the gut microbiota in regulating human health and disease has however been largely overlooked due to the inaccessibility of the intestinal habitat, the complexity of the gut microbiota itself and the fact that many of its members resist cultivation and are in fact new to science. However, with the emergence of 16S rRNA molecular tools and "post-genomics" high resolution technologies for examining microorganisms as they occur in nature without the need for prior laboratory culture, this limited view of the gut microbiota is rapidly changing. This review will discuss the application of molecular microbiological tools to study the human gut microbiota in a culture independent manner. Genomics or metagenomics approaches have a tremendous capability to generate compositional data and to measure the metabolic potential encoded by the combined genomes of the gut microbiota. Another post-genomics approach, metabonomics, has the capacity to measure the metabolic kinetic or flux of metabolites through an ecosystem at a particular point in time or over a time course. Metabonomics thus derives data on the function of the gut microbiota in situ and how it responds to different environmental stimuli e.g. substrates like prebiotics, antibiotics and other drugs and in response to disease. Recently these two culture independent, high resolution approaches have been combined into a single "trans-genomic" approach which allows correlation of changes in metabolite profiles within human biofluids with microbiota compositional metagenomic data. Such approaches are providing novel insight into the composition, function and evolution of our gut microbiota.

  7. Study of gene transfer in vitro and in the digestive tract of gnotobiotic mice from Lactococcus lactis strains to various strains belonging to human intestinal flora.

    PubMed

    Gruzza, M; Fons, M; Ouriet, M F; Duval-Iflah, Y; Ducluzeau, R

    1994-07-01

    The use of genetically modified organisms (GMO) in dairy products requires evaluation of the DNA transfer capacity from such organisms among the human intestinal microflora. Thus, both in vitro and in vivo [in the digestive tract (DT) of mice] transfer from Lactococcus lactis donor strains of the conjugative plasmid pIL205 (CmR) and the non-conjugative plasmid pIL253 (EmR) to: (1) recipient strains isolated from human faecal flora Bacteroides sp., Bifidobacterium sp., Peptostreptococcus sp. (strictly anaerobic bacterial strains) and Enterococcus faecalis, (2) a whole human faecal flora, was studied. In both cases, no gene transfer was observed to strictly anaerobic bacterial strains. DNA transfer was only observed to the E. faecalis strain: in vivo CmR E. faecalis transconjugants were isolated from sequentially multi-associated mice and when the recipient strains associated with the mice, they were a defined mixture of Bacteroides sp., Bifidobacterium sp., Peptostreptococcus sp. and E. faecalis strains. When mice were associated with the whole human faecal flora, the plasmid pIL205 was transferred into some facultative anaerobic streptococci. It was also shown that DNA transfer occurred even when the lactococcal donor strain was transient in the DT of the gnotobiotic host animals.

  8. Arsenic Metabolism by Human Gut Microbiota upon in Vitro Digestion of Contaminated Soils

    PubMed Central

    Van de Wiele, Tom; Gallawa, Christina M.; Kubachk, Kevin M.; Creed, John T.; Basta, Nicholas; Dayton, Elizabeth A.; Whitacre, Shane; Laing, Gijs Du; Bradham, Karen

    2010-01-01

    Background Speciation analysis is essential when evaluating risks from arsenic (As) exposure. In an oral exposure scenario, the importance of presystemic metabolism by gut microorganisms has been evidenced with in vivo animal models and in vitro experiments with animal microbiota. However, it is unclear whether human microbiota display similar As metabolism, especially when present in a contaminated matrix. Objectives We evaluated the metabolic potency of in vitro cultured human colon microbiota toward inorganic As (iAs) and As-contaminated soils. Methods A colon microbial community was cultured in a dynamic model of the human gut. These colon microbiota were incubated with iAs and with As-contaminated urban soils. We determined As speciation analysis using high-performance liquid chromatography coupled with inductively coupled plasma mass spectrometry. Results We found a high degree of methylation for colon digests both of iAs (10 μg methylarsenical/g biomass/hr) and of As-contaminated soils (up to 28 μg/g biomass/hr). Besides the formation of monomethylarsonic acid (MMAV), we detected the highly toxic monomethylarsonous acid (MMAIII). Moreover, this is the first description of microbial thiolation leading to monomethylmonothioarsonic acid (MMMTAV). MMMTAV, the toxicokinetic properties of which are not well known, was in many cases a major metabolite. Conclusions Presystemic As metabolism is a significant process in the human body. Toxicokinetic studies aiming to completely elucidate the As metabolic pathway would therefore benefit from incorporating the metabolic potency of human gut microbiota. This will result in more accurate risk characterization associated with As exposures. PMID:20603239

  9. A discrete genetic locus confers xyloglucan metabolism in select human gut Bacteroidetes

    PubMed Central

    Larsbrink, Johan; Rogers, Theresa E.; Hemsworth, Glyn R.; McKee, Lauren S.; Tauzin, Alexandra S.; Spadiut, Oliver; Klinter, Stefan; Pudlo, Nicholas A.; Urs, Karthik; Koropatkin, Nicole M.; Creagh, A. Louise; Haynes, Charles A.; Kelly, Amelia G.; Cederholm, Stefan Nilsson; Davies, Gideon J.; Martens, Eric C.; Brumer, Harry

    2014-01-01

    A well-balanced human diet includes a significant intake of non-starch polysaccharides, collectively termed “dietary fibre,” from the cell walls of diverse fruits and vegetables.1 Due to a paucity of alimentary enzymes encoded by the human genome,2 our ability to derive energy from dietary fibre depends on saccharification and fermentation of complex carbohydrates by the massive microbial community residing in our distal gut.3,4 The xyloglucans (XyGs), in particular, are a ubiquitous family of highly branched plant cell wall polysaccharides5,6 whose mechanism(s) of degradation in the human gut and consequent importance in nutrition was heretofore unknown.1,7,8 Here, we demonstrate that a single, complex gene locus in Bacteroides ovatus confers xyloglucan catabolism in this common colonic symbiont. Through targeted gene disruption, biochemical analysis of all predicted glycoside hydrolases and carbohydrate-binding proteins, and three-dimensional structural determination of the vanguard endo-xyloglucanase, we reveal the molecular mechanisms through which XyGs are hydrolysed to component monosaccharides for further metabolism. We also observe that orthologous xyloglucan utilization loci (XyGULs) serve as genetic markers of xyloglucan catabolism in Bacteroidetes, that XyGULs are restricted to a limited number of phylogenetically diverse strains, and that XyGULs are ubiquitous in surveyed human metagenomes. Our findings reveal that the metabolism of even highly abundant components of dietary fibre may be mediated by niche species, which has immediate fundamental and practical implications for gut symbiont population ecology in the context of human diet, nutrition and health.9–12 PMID:24463512

  10. IDO in human gut graft-versus-host disease.

    PubMed

    Ratajczak, Philippe; Janin, Anne; Peffault de Larour, Régis; Koch, Lisa; Roche, Brigitte; Munn, David; Blazar, Bruce R; Socié, Gérard

    2012-01-01

    Although rodent graft-versus-host disease (GVHD) models have suggested that indoleamine 2,3-dioxygenase (IDO) is a critical regulator of gastrointestinal GVHD, parallel human studies on IDO expression have not been reported. IDO expression was assessed in 20 patients who underwent duodenal biopsy. IDO was upregulated in epithelial cells. In situ analyses reveal that macrophages and dendritic cells stain positive for IDO, but that most of the IDO(+) cells were a novel population of CD3(+)CD4(+)IDO(+) cells. The proportion of CD4(+)IDO(+) T cells was significantly higher in patients with moderate GVHD. In situ regulatory T cell and Th17 numbers correlated with overall severity. Although needing confirmatory results from larger sample sets, these data are consistent with the hypothesis that IDO is involved in regulating gastrointestinal GVHD.

  11. Metaproteomics Reveals Functional Shifts in Microbial and Human Proteins During Infant Gut Colonization Case

    SciTech Connect

    Young, Jacque C.; Pan, Chongle; Adams, Rachel M.; Brooks, Brandon; Banfield, Jillian F.; Morowitz, Michael J.; Robert L. Hettich

    2015-01-01

    The microbial colonization of the human gastrointestinal tract plays an important role in establishing health and homeostasis. However, the time-dependent functional signatures of microbial and human proteins during early colonization of the gut have yet to be determined. Thus, we employed shotgun proteomics to simultaneously monitor microbial and human proteins in fecal samples from a preterm infant during the first month of life. Microbial community complexity and functions increased over time, with compositional changes that were consistent with previous metagenomic and rRNA gene data indicating three distinct colonization phases. Overall microbial community functions were established relatively early in development and remained stable. Human proteins detected included those responsible for epithelial barrier function and antimicrobial activity. Some neutrophil-derived proteins increased in abundance early in the study period, suggesting activation of the innate immune system. Moreover, abundances of cytoskeletal and mucin proteins increased later in the time course, suggestive of subsequent adjustment to the increased microbial load. Our study provides the first snapshot of coordinated human and microbial protein expression in the infant gut during early development.

  12. Metaproteomics Reveals Functional Shifts in Microbial and Human Proteins During Infant Gut Colonization Case

    DOE PAGES

    Young, Jacque C.; Pan, Chongle; Adams, Rachel M.; Brooks, Brandon; Banfield, Jillian F.; Morowitz, Michael J.; Robert L. Hettich

    2015-01-01

    The microbial colonization of the human gastrointestinal tract plays an important role in establishing health and homeostasis. However, the time-dependent functional signatures of microbial and human proteins during early colonization of the gut have yet to be determined. Thus, we employed shotgun proteomics to simultaneously monitor microbial and human proteins in fecal samples from a preterm infant during the first month of life. Microbial community complexity and functions increased over time, with compositional changes that were consistent with previous metagenomic and rRNA gene data indicating three distinct colonization phases. Overall microbial community functions were established relatively early in development andmore » remained stable. Human proteins detected included those responsible for epithelial barrier function and antimicrobial activity. Some neutrophil-derived proteins increased in abundance early in the study period, suggesting activation of the innate immune system. Moreover, abundances of cytoskeletal and mucin proteins increased later in the time course, suggestive of subsequent adjustment to the increased microbial load. Our study provides the first snapshot of coordinated human and microbial protein expression in the infant gut during early development.« less

  13. In Vitro Method To Assess Soil Arsenic Metabolism by Human Gut Microbiota: Arsenic Speciation and Distribution.

    PubMed

    Yin, Naiyi; Zhang, Zhennan; Cai, Xiaolin; Du, Huili; Sun, Guoxin; Cui, Yanshan

    2015-09-01

    Arsenic (As) speciation and distribution are two important factors in assessing human health risk from As-contaminated soil. In this study, we used the combination of physiologically based extraction test (PBET) and Simulator of Human Intestinal Microbial Ecosystem (SHIME) to determine soil As metabolism by human gut microbiota. The results showed that the percentage of soil arsenate [As(V)] transformation reached 22.1-38.2%, while that of arsenite [As(III)] attained 66.5-92.0%; 30.1-56.4% of As(V) transformed was attached to the soil solid phase. In comparison to sequential extraction results, almost all amorphous Fe/Al-oxide-bound As was liberated in the colon phase. An X-ray absorption near-edge structure (XANES) showed that the As(III) percentage in the soil solid phase reached 16.6-26.9% and reached 73.4% (soil 1) in the colon phase. Additionally, plenty of As(III) and different extents of methylation were also observed in colon extraction solution. As bioaccessibility in the colon phase was 1.8-2.8 times that in the small intestinal phase. Our results indicated that human gut microbiota increased As bioaccessibility, and large amounts of As(III) were adsorbed onto the soil solid phase as a result of microbial reduction. Determining As speciation and distribution in extraction solution and soil solid phases will allow for an accurate assessment of the risk to human health upon soil As exposure. PMID:26248026

  14. The antimicrobial activity of embalming chemicals and topical disinfectants on the microbial flora of human remains.

    PubMed

    Burke, P A; Sheffner, A L

    1976-10-01

    The antimicrobial activity of embalming chemicals an topical disinfectants was evaluated to determine the degree of disinfection achieved during the embalming of human remains. The administration of arterial and cavity embalming chemicals resulted in a 99% reduction of the postmortem microbial population after 2 hours of contact. This level of disinfection was maintained for the 24 hours test period. Topical disinfection of the body orifices was also observed. Therefore, it is probable that present embalming practices reduce the hazard from transmission of potentially infectious microbial agents within the immediate environment of embalmed human remains.

  15. Evidence for plasmid-mediated salt tolerance in the human gut microbiome and potential mechanisms.

    PubMed

    Broaders, Eileen; O'Brien, Ciarán; Gahan, Cormac G M; Marchesi, Julian R

    2016-03-01

    The human gut microbiome is critical to health and wellbeing. It hosts a complex ecosystem comprising a multitude of bacterial species, which contributes functionality that would otherwise be absent from the host. Transient and commensal bacteria in the gut must withstand many stresses. The influence of mobile genetic elements such as plasmids in stress adaptation within the ecosystem is poorly understood. Using a mobilomic approach we found evidence for plasmid-mediated osmotolerance as a phenotype amongst the Proteobacteria in healthy faecal slurries. A transconjugant carrying multiple plasmids acquired from healthy faecal slurry demonstrated increased osmotolerance in the presence of metal salts, particularly potassium chloride, which was not evident in the recipient. Pyrosequencing and analysis of the total plasmid DNA demonstrated the presence of plasmid-borne osmotolerance systems (including KdpD and H-NS) which may be linked to the observed phenotype. This is the first report of a transferable osmotolerance phenotype in gut commensals and may have implications for the transfer of osmotolerance in other niches.

  16. The Impact of Diet and Lifestyle on Gut Microbiota and Human Health

    PubMed Central

    Conlon, Michael A.; Bird, Anthony R.

    2014-01-01

    There is growing recognition of the role of diet and other environmental factors in modulating the composition and metabolic activity of the human gut microbiota, which in turn can impact health. This narrative review explores the relevant contemporary scientific literature to provide a general perspective of this broad area. Molecular technologies have greatly advanced our understanding of the complexity and diversity of the gut microbial communities within and between individuals. Diet, particularly macronutrients, has a major role in shaping the composition and activity of these complex populations. Despite the body of knowledge that exists on the effects of carbohydrates there are still many unanswered questions. The impacts of dietary fats and protein on the gut microbiota are less well defined. Both short- and long-term dietary change can influence the microbial profiles, and infant nutrition may have life-long consequences through microbial modulation of the immune system. The impact of environmental factors, including aspects of lifestyle, on the microbiota is particularly poorly understood but some of these factors are described. We also discuss the use and potential benefits of prebiotics and probiotics to modify microbial populations. A description of some areas that should be addressed in future research is also presented. PMID:25545101

  17. Long-Term Green Tea Supplementation Does Not Change the Human Gut Microbiota

    PubMed Central

    Janssens, Pilou L. H. R.; Penders, John; Hursel, Rick; Budding, Andries E.; Savelkoul, Paul H. M.; Westerterp-Plantenga, Margriet S.

    2016-01-01

    Background Green tea catechins may play a role in body weight regulation through interactions with the gut microbiota. Aim We examined whether green tea supplementation for 12 weeks induces changes in composition of the human gut microbiota. Methods 58 Caucasian men and women were included in a randomized, placebo-controlled design. For 12 weeks, subjects consumed either green tea (>0.56 g/d epigallocatechin-gallate + 0.28 ∼ 0.45 g/d caffeine) or placebo capsules. Fecal samples were collected twice (baseline, vs. week 12) for analyses of total bacterial profiles by means of IS-profiling, a 16S-23S interspacer region-based profiling method. Results No significant changes between baseline and week 12 in subjects receiving green tea or placebo capsules, and no significant interactions between treatment (green tea or placebo) and time (baseline and week 12) were observed for body composition. Analysis of the fecal samples in subjects receiving green tea and placebo showed similar bacterial diversity and community structures, indicating there were no significant changes in bacterial diversity between baseline and week 12 in subjects receiving green tea capsules or in subjects receiving placebo capsules. No significant interactions were observed between treatment (green tea or placebo) and time (baseline and week 12) for the gut microbial diversity. Although, there were no significant differences between normal weight and overweight subjects in response to green tea, we did observe a reduced bacterial alpha diversity in overweight as compared to normal weight subjects (p = 0.002). Conclusion Green tea supplementation for 12 weeks did not have a significant effect on composition of the gut microbiota. Trial Registration ClinicalTrials.gov NCT01556321 PMID:27054321

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

    PubMed

    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. PMID:26891629

  19. The human gut virome: inter-individual variation and dynamic response to diet.

    PubMed

    Minot, Samuel; Sinha, Rohini; Chen, Jun; Li, Hongzhe; Keilbaugh, Sue A; Wu, Gary D; Lewis, James D; Bushman, Frederic D

    2011-10-01

    Immense populations of viruses are present in the human gut and other body sites. Understanding the role of these populations (the human "virome") in health and disease requires a much deeper understanding of their composition and dynamics in the face of environmental perturbation. Here, we investigate viromes from human subjects on a controlled feeding regimen. Longitudinal fecal samples were analyzed by metagenomic sequencing of DNA from virus-like particles (VLP) and total microbial communities. Assembly of 336 Mb of VLP sequence yielded 7175 contigs, many identifiable as complete or partial bacteriophage genomes. Contigs were rich in viral functions required in lytic and lysogenic growth, as well as unexpected functions such as viral CRISPR arrays and genes for antibiotic resistance. The largest source of variance among virome samples was interpersonal variation. Parallel deep-sequencing analysis of bacterial populations showed covaration of the virome with the larger microbiome. The dietary intervention was associated with a change in the virome community to a new state, in which individuals on the same diet converged. Thus these data provide an overview of the composition of the human gut virome and associate virome structure with diet. PMID:21880779

  20. Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances

    PubMed Central

    Francino, M. P.

    2016-01-01

    The human microbiome is overly exposed to antibiotics, due, not only to their medical use, but also to their utilization in farm animals and crops. Microbiome composition can be rapidly altered by exposure to antibiotics, with potential immediate effects on health, for instance through the selection of resistant opportunistic pathogens that can cause acute disease. Microbiome alterations induced by antibiotics can also indirectly affect health in the long-term. The mutualistic microbes in the human body interact with many physiological processes, and participate in the regulation of immune and metabolic homeostasis. Therefore, antibiotic exposure can alter many basic physiological equilibria, promoting long-term disease. In addition, excessive antibiotic use fosters bacterial resistance, and the overly exposed human microbiome has become a significant reservoir of resistance genes, contributing to the increasing difficulty in controlling bacterial infections. Here, the complex relationships between antibiotics and the human microbiome are reviewed, with focus on the intestinal microbiota, addressing (1) the effects of antibiotic use on the composition and function of the gut microbiota, (2) the impact of antibiotic-induced microbiota alterations on immunity, metabolism, and health, and (3) the role of the gut microbiota as a reservoir of antibiotic resistances. PMID:26793178

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

    PubMed

    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.

  2. Dining in with Trillions of Fascinating Friends: Exploring Our Human Gut Microbiome in Health and Disease

    PubMed Central

    Gordon, J.I.

    2011-01-01

    Our genetic landscape is a summation of the genes embedded in our human genome and in the genomes of our microbial symbionts (the microbiome). Similarly, our metabolic features (metabotypes) are an amalgamation of human and microbial traits. Therefore, understanding of the range of human genetic and metabolic diversity means that we must characterize our microbiomes, which contain at least several hundred-fold more genes than our human genome, as well as the factors that influence the properties of our microbial communities (microbiota). The results should provide an additional perspective about contemporary human biology as we assess how our changing lifestyles, cultural norms, socioeconomic status, and biosphere are influencing our microbial ecology and health status. I will discuss the results of our group's ongoing metagenomic studies of the interrelationships between diet and the structure and dynamic operations of the human gut microbiome. We believe that understanding these interrelationships is important for advancing our appreciation of the nutritional value of food ingredients, for creating new nutritional guidelines for humans at various stages of their lifespan, and for developing new ways to deliberately manipulate the properties of the gut microbiota to prevent or treat various diseases. We have developed a translational medicine pipeline that involves metagenomic analyses of the gut microbial communities of adult mono- and dizygotic twins living in the USA who are lean, or concordant or discordant for obesity, and twins aged 0–3 years living in developing countries who develop normally, or who become malnourished and are treated with a ready-to-use therapeutic food (RUTF). Intact fecal communities from these individuals, or ‘personal’ culture collections that capture the majority of bacterial diversity in their microbiota, are then transplanted into germ-free mice, which are fed the diets of the human donors, or systematically manipulated

  3. Immune Disorders and Its Correlation with Gut Microbiome

    PubMed Central

    Hwang, Ji-Sun; Im, Chang-Rok

    2012-01-01

    Allergic disorders such as atopic dermatitis and asthma are common hyper-immune disorders in industrialized countries. Along with genetic association, environmental factors and gut microbiota have been suggested as major triggering factors for the development of atopic dermatitis. Numerous studies support the association of hygiene hypothesis in allergic immune disorders that a lack of early childhood exposure to diverse microorganism increases susceptibility to allergic diseases. Among the symbiotic microorganisms (e.g. gut flora or probiotics), probiotics confer health benefits through multiple action mechanisms including modification of immune response in gut associated lymphoid tissue (GALT). Although many human clinical trials and mouse studies demonstrated the beneficial effects of probiotics in diverse immune disorders, this effect is strain specific and needs to apply specific probiotics for specific allergic diseases. Herein, we briefly review the diverse functions and regulation mechanisms of probiotics in diverse disorders. PMID:23091436

  4. Proteobacteria: microbial signature of dysbiosis in gut microbiota.

    PubMed

    Shin, Na-Ri; Whon, Tae Woong; Bae, Jin-Woo

    2015-09-01

    Recent advances in sequencing techniques, applied to the study of microbial communities, have provided compelling evidence that the mammalian intestinal tract harbors a complex microbial community whose composition is a critical determinant of host health in the context of metabolism and inflammation. Given that an imbalanced gut microbiota often arises from a sustained increase in abundance of the phylum Proteobacteria, the natural human gut flora normally contains only a minor proportion of this phylum. Here, we review studies that explored the association between an abnormal expansion of Proteobacteria and a compromised ability to maintain a balanced gut microbial community. We also propose that an increased prevalence of Proteobacteria is a potential diagnostic signature of dysbiosis and risk of disease. PMID:26210164

  5. Detecting human impacts on the flora, fauna, and summer monsoon of Pleistocene Australia

    NASA Astrophysics Data System (ADS)

    Miller, G. H.; Magee, J. W.; Fogel, M. L.; Gagan, M. K.

    2006-08-01

    All of Australia's largest mammalian vertebrates became extinct 50 to 45 ka (thousand years ago), shortly after human colonization. Between 60 and 40 ka Australian climate was similar to present and not changing rapidly. Consequently, attention has turned toward plausible human mechanisms for the extinction, with proponents for over-hunting, ecosystem change, and introduced disease. To differentiate between these options we utilize isotopic tracers of diet preserved in eggshells of two large, flightless birds to track the status of ecosystems before and after human colonization. δ13C preserved in their eggshells monitor a bird's dietary intake in the weeks to months before egg-laying. More than 500 dated eggshells from central Australia of the Australian emu (Dromaius novaehollandiae), an opportunistic, dominantly herbivorous feeder, provide a continuous 140 kyr dietary δ 13C reconstruction. More than 350 dated eggshells from the same region of the heavier, extinct, giant bird Genyornis newtoni define its dietary intake from 140 ka until its extinction about 50 ka. Additional dietary records for both species were developed from two distant regions. Dromaius eggshell dietary δ13C reveals an unprecedented reduction in the bird's food resources about 50 ka, coeval in all three regions, suggesting conversion at that time of a tree/shrub savannah with occasionally rich grasslands to the modern desert scrub. We speculate that ecosystem collapse across the arid and semi-arid zones is a consequence of systematic burning by early humans. Genyornis diet everywhere is more restricted than in co-existing Dromaius, implying a more specialized feeding strategy. These data suggest that generalist feeders, such as Dromaius, were able to adapt to a changed vegetation regime, whereas more specialized feeders, such as Genyornis, became extinct. The altered vegetation may have also impacted Australian climate. Changes in the strength of climate feedbacks linked to vegetation and

  6. Detecting human impacts on the flora, fauna, and summer monsoon of Pleistocene Australia

    NASA Astrophysics Data System (ADS)

    Miller, G. H.; Magee, J. W.; Fogel, M. L.; Gagan, M. K.

    2007-08-01

    The moisture balance across northern and central Australia is dominated by changes in the strength of the Australian Summer Monsoon. Lake-level records that record changes in monsoon strength on orbital timescales are most consistent with a Northern Hemisphere insolation control on monsoon strength, a result consistent with recent modeling studies. A weak Holocene monsoon relative to monsoon strength 65-60 ka, despite stronger forcing, suggests a changed monsoon regime after 60 ka. Shortly after 60 ka humans colonized Australia and all of Australia's largest mammals became extinct. Between 60 and 40 ka Australian climate was similar to present and not changing rapidly. Consequently, attention has turned toward plausible human mechanisms for the extinction, with proponents for over-hunting, ecosystem change, and introduced disease. To differentiate between these options we utilize isotopic tracers of diet preserved in eggshells of two large, flightless birds to track the status of ecosystems before and after human colonization. More than 800 dated eggshells of the Australian emu (Dromaius novaehollandiae), an opportunistic, dominantly herbivorous feeder, provide a 140-kyr dietary reconstruction that reveals unprecedented reduction in the bird's food resources about 50 ka, coeval in three distant regions. These data suggest a tree/shrub savannah with occasionally rich grasslands was converted abruptly to the modern desert scrub. The diet of the heavier, extinct Genyornis newtoni, derived from >550 dated eggshells, was more restricted than in co-existing Dromaius, implying a more specialized feeding strategy. We suggest that generalist feeders, such as Dromaius, were able to adapt to a changed vegetation regime, whereas more specialized feeders, such as Genyornis, became extinct. We speculate that ecosystem collapse across arid and semi-arid zones was a consequence of systematic burning by early humans. We also suggest that altered climate feedbacks linked to changes

  7. A novel transcriptional regulator of L-arabinose utilization in human gut bacteria

    SciTech Connect

    Chang, Changsoo; Tesar, Christine; Li, Xiaoqing; Kim, Youngchang; Rodionov, Dmitry A.; Joachimiak, Andrzej

    2015-10-04

    We report that carbohydrate metabolism plays a crucial role in the ecophysiology of human gut microbiota. Mechanisms of transcriptional regulation of sugar catabolism in commensal and prevalent human gut bacteria such as Bacteroides thetaiotaomicron remain mostly unknown. By a combination of bioinformatics and experimental approaches, we have identified an NrtR family transcription factor (BT0354 in B. thetaiotaomicron, BtAraR) as a novel regulator controlling the arabinose utilization genes. L-arabinose was confirmed to be a negative effector of BtAraR. We have solved the crystal structures of the apo and L-arabinose-bound BtAraR proteins, as well as the complex of apo-protein with a specific DNA operator. BtAraR forms a homodimer with each subunit comprised of the ligand-binding Nudix hydrolase-like domain and the DNA-binding winged-helix-turn-helix (wHTH) domain. We have identified the residues involved in binding of L-arabinose and recognition of DNA. The majority of these residues are well conserved in the AraR orthologs in Bacteroidetes. In the structure of the BtAraR–DNA complex, we found the unique interaction of arginine intercalating its guanidinum moiety into the base pair stacking of B-DNA. L-arabinose binding induces movement of wHTH domains, resulting in a conformation unsuitable for DNA binding. Furthermore, our analysis facilitates reconstruction of the metabolic and regulatory networks involved in carbohydrate utilization in human gut Bacteroides.

  8. A novel transcriptional regulator of L-arabinose utilization in human gut bacteria

    DOE PAGES

    Chang, Changsoo; Tesar, Christine; Li, Xiaoqing; Kim, Youngchang; Rodionov, Dmitry A.; Joachimiak, Andrzej

    2015-10-04

    We report that carbohydrate metabolism plays a crucial role in the ecophysiology of human gut microbiota. Mechanisms of transcriptional regulation of sugar catabolism in commensal and prevalent human gut bacteria such as Bacteroides thetaiotaomicron remain mostly unknown. By a combination of bioinformatics and experimental approaches, we have identified an NrtR family transcription factor (BT0354 in B. thetaiotaomicron, BtAraR) as a novel regulator controlling the arabinose utilization genes. L-arabinose was confirmed to be a negative effector of BtAraR. We have solved the crystal structures of the apo and L-arabinose-bound BtAraR proteins, as well as the complex of apo-protein with a specificmore » DNA operator. BtAraR forms a homodimer with each subunit comprised of the ligand-binding Nudix hydrolase-like domain and the DNA-binding winged-helix-turn-helix (wHTH) domain. We have identified the residues involved in binding of L-arabinose and recognition of DNA. The majority of these residues are well conserved in the AraR orthologs in Bacteroidetes. In the structure of the BtAraR–DNA complex, we found the unique interaction of arginine intercalating its guanidinum moiety into the base pair stacking of B-DNA. L-arabinose binding induces movement of wHTH domains, resulting in a conformation unsuitable for DNA binding. Furthermore, our analysis facilitates reconstruction of the metabolic and regulatory networks involved in carbohydrate utilization in human gut Bacteroides.« less

  9. Gnotobiotic mouse model of phage–bacterial host dynamics in the human gut

    PubMed Central

    Reyes, Alejandro; Wu, Meng; McNulty, Nathan P.; Rohwer, Forest L.; Gordon, Jeffrey I.

    2013-01-01

    Bacterial viruses (phages) are the most abundant biological group on Earth and are more genetically diverse than their bacterial prey/hosts. To characterize their role as agents shaping gut microbial community structure, adult germ-free mice were colonized with a consortium of 15 sequenced human bacterial symbionts, 13 of which harbored one or more predicted prophages. One member, Bacteroides cellulosilyticus WH2, was represented by a library of isogenic transposon mutants that covered 90% of its genes. Once assembled, the community was subjected to a staged phage attack with a pool of live or heat-killed virus-like particles (VLPs) purified from the fecal microbiota of five healthy humans. Shotgun sequencing of DNA from the input pooled VLP preparation plus shotgun sequencing of gut microbiota samples and purified fecal VLPs from the gnotobiotic mice revealed a reproducible nonsimultaneous pattern of attack extending over a 25-d period that involved five phages, none described previously. This system allowed us to (i) correlate increases in specific phages present in the pooled VLPs with reductions in the representation of particular bacterial taxa, (ii) provide evidence that phage resistance occurred because of ecological or epigenetic factors, (iii) track the origin of each of the five phages among the five human donors plus the extent of their genome variation between and within recipient mice, and (iv) establish the dramatic in vivo fitness advantage that a locus within a B. cellulosilyticus prophage confers upon its host. Together, these results provide a defined community-wide view of phage–bacterial host dynamics in the gut. PMID:24259713

  10. Direct sequencing of human gut virome fractions obtained by flow cytometry.

    PubMed

    Džunková, Mária; D'Auria, Giuseppe; Moya, Andrés

    2015-01-01

    The sequence assembly of the human gut virome encounters several difficulties. A high proportion of human and bacterial matches is detected in purified viral samples. Viral DNA extraction results in a low DNA concentration, which does not reach the minimal limit required for sequencing library preparation. Therefore, the viromes are usually enriched by whole genome amplification (WGA), which is, however, prone to the development of chimeras and amplification bias. In addition, as there is a very wide diversity of gut viral species, very extensive sequencing efforts must be made for the assembling of whole viral genomes. We present an approach to improve human gut virome assembly by employing a more precise preparation of a viral sample before sequencing. Particles present in a virome previously filtered through 0.2 μm pores were further divided into groups in accordance with their size and DNA content by fluorescence activated cell sorting (FACS). One selected viral fraction was sequenced excluding the WGA step, so that unbiased sequences with high reliability were obtained. The DNA extracted from the 314 viral particles of the selected fraction was assembled into 34 contigs longer than 1,000 bp. This represents an increase to the number of assembled long contigs per sequenced Gb in comparison with other studies where non-fractioned viromes are sequenced. Seven of these contigs contained open reading frames (ORFs) with explicit matches to proteins related to bacteriophages. The remaining contigs also possessed uncharacterized ORFs with bacteriophage-related domains. When the particles that are present in the filtered viromes are sorted into smaller groups by FACS, large pieces of viral genomes can be recovered easily. This approach has several advantages over the conventional sequencing of non-fractioned viromes: non-viral contamination is reduced and the sequencing efforts required for viral assembly are minimized. PMID:26441889

  11. Identifying Keystone Species in the Human Gut Microbiome from Metagenomic Timeseries Using Sparse Linear Regression

    PubMed Central

    Fisher, Charles K.; Mehta, Pankaj

    2014-01-01

    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 the human

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

    PubMed

    Fisher, Charles K; Mehta, Pankaj

    2014-01-01

    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 the human gut

  13. Characterization and Detection of a Widely Distributed Gene Cluster That Predicts Anaerobic Choline Utilization by Human Gut Bacteria

    PubMed Central

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

    2015-01-01

    ABSTRACT 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. PMID:25873372

  14. The Impact of the Gut Microbiota on Human Health: An Integrative View

    PubMed Central

    Clemente, Jose C.; Ursell, Luke K.; Parfrey, Laura Wegener; Knight, Rob

    2016-01-01

    The human gut harbors diverse microbes that play a fundamental role in the well-being of their host. The constituents of the microbiota—bacteria, viruses, and eukaryotes—have been shown to interact with one another and with the host immune system in ways that influence the development of disease. We review these interactions and suggest that a holistic approach to studying the microbiota that goes beyond characterization of community composition and encompasses dynamic interactions between all components of the microbiota and host tissue over time will be crucial for building predictive models for diagnosis and treatment of diseases linked to imbalances in our microbiota. PMID:22424233

  15. Fate and effect of ingested Bacillus cereus spores and vegetative cells in the intestinal tract of human-flora-associated rats.

    PubMed

    Wilcks, Andrea; Hansen, Bjarne Munk; Hendriksen, Niels Bohse; Licht, Tine Rask

    2006-02-01

    The fate and effect of Bacillus cereus F4433/73R in the intestine of human-flora-associated rats was studied using bacteriological culturing techniques and PCR-denaturing gradient gel electrophoresis in combination with cell assays and immunoassays for detection of enterotoxins. In faecal samples from animals receiving vegetative cells, only few B. cereus cells were detected. Spores survived the gastric barrier well, and were in some cases detected up to 2 weeks after ingestion. Selective growing revealed no major changes in the intestinal flora during passage of B. cereus. However, denaturing gradient gel electrophoresis analysis with universal 16S rRNA gene primers revealed significant changes in the intestinal microbiota of animals dosed with spores. Vero cell assays and a commercial kit (BCET-RPLA) did not reveal any enterotoxin production from B. cereus F4433/73R in the intestinal tract.

  16. Susceptibility and tolerance of human gut culturable aerobic microbiota to wine polyphenols.

    PubMed

    Cueva, Carolina; Bartolomé, Begoña; Moreno-Arribas, M Victoria; Bustos, Irene; Requena, Teresa; González-Manzano, Susana; Santos-Buelga, Celestino; Turrientes, María-Carmen; del Campo, Rosa

    2015-02-01

    Diet is one of the main factors that could affect quantitatively and qualitatively the stability of the gut microbiota. Polyphenols are abundantly present in the human diet and have an antimicrobial effect inducing selective changes in the microbiota composition, with potential beneficial effects for the human health. Our aim was to determine the human gut microbiota susceptibility toward wine polyphenols. Susceptibility to two commercial wine phenolic extracts (Vitaflavan(®) and Provinols™) was determined in isolates from fecal samples from 36 gastrointestinal healthy volunteers. To select the polyphenol-resistant isolates, feces were seeded in plates containing 1 mg/ml of phenolic extract. The minimal inhibitory concentration to polyphenols in the collected isolates was assessed by the agar dilution method. Overall results showed that Gram-negative isolates are most tolerant to the presence of both grape seed and red wine extracts. Furthermore, we purified to homogeneity the phenolic fractions by high-performance liquid chromatography (HPLC) to determine their antimicrobial effect and their influence on bacterial growth in four selected ATCC strains using the BioScreen apparatus. Results showed that the antimicrobial activity of the wine polyphenols is the result of the interaction of both the flavan-3-ol type and the bacteria. Bacterial Intraspecies differences in the phenolic susceptibility suggest the existence of polyphenol-resistant mechanisms that are uncharacterized as yet.

  17. Different human gut models reveal the distinct fermentation patterns of Arabinoxylan versus inulin.

    PubMed

    Van den Abbeele, Pieter; Venema, Koen; Van de Wiele, Tom; Verstraete, Willy; Possemiers, Sam

    2013-10-16

    Different in vitro models have been developed to assess how food compounds affect the human gut microbiota. Using two such models (SHIME(R) and TIM-2), we compared how long-chain arabinoxylan (LC-AX), a wheat-derived potentially prebiotic fiber, and inulin (IN), a well-established prebiotic compound, modulate SCFA production and bifidobacteria composition. While both the SHIME and TIM-2 differ in experimental design, they both demonstrated that LC-AX and IN specifically increased the health-promoting metabolites propionate and butyrate, respectively. Furthermore, LC-AX stimulated Bifidobacterium longum, while IN stimulated other bifidobacteria including Bifidobacterium adolescentis. The SHIME experiment also revealed that effects of LC-AX were more persistent during the 2-week wash-out period. These results confirm a recent in vivo study, during which humanized rats were treated with the same LC-AX/IN. In conclusion, results from different human gut models suggest that, besides IN, LC-AX are promising prebiotic candidates with high specificity toward Bifidobacterium longum and a selective propionate increase.

  18. Functional metagenomics reveals novel pathways of prebiotic breakdown by human gut bacteria.

    PubMed

    Cecchini, Davide A; Laville, Elisabeth; Laguerre, Sandrine; Robe, Patrick; Leclerc, Marion; Doré, Joël; Henrissat, Bernard; Remaud-Siméon, Magali; Monsan, Pierre; Potocki-Véronèse, Gabrielle

    2013-01-01

    The human intestine hosts a complex bacterial community that plays a major role in nutrition and in maintaining human health. A functional metagenomic approach was used to explore the prebiotic breakdown potential of human gut bacteria, including non-cultivated ones. Two metagenomic libraries, constructed from ileum mucosa and fecal microbiota, were screened for hydrolytic activities on the prebiotic carbohydrates inulin, fructo-oligosaccharides, xylo-oligosaccharides, galacto-oligosaccharides and lactulose. The DNA inserts of 17 clones, selected from the 167 hits that were identified, were pyrosequenced in-depth, yielding in total 407, 420 bp of metagenomic DNA. From these sequences, we discovered novel prebiotic degradation pathways containing carbohydrate transporters and hydrolysing enzymes, for which we provided the first experimental proof of function. Twenty of these proteins are encoded by genes that are also present in the gut metagenome of at least 100 subjects, whatever are their ages or their geographical origin. The sequence taxonomic assignment indicated that still unknown bacteria, for which neither culture conditions nor genome sequence are available, possess the enzymatic machinery to hydrolyse the prebiotic carbohydrates tested. The results expand the vision on how prebiotics are metabolized along the intestine, and open new perspectives for the design of functional foods.

  19. Functional Metabolic Map of Faecalibacterium prausnitzii, a Beneficial Human Gut Microbe

    PubMed Central

    Heinken, Almut; Khan, M. Tanweer; Paglia, Giuseppe; Rodionov, Dmitry A.; Harmsen, Hermie J. M.

    2014-01-01

    The human gut microbiota plays a central role in human well-being and disease. In this study, we present an integrated, iterative approach of computational modeling, in vitro experiments, metabolomics, and genomic analysis to accelerate the identification of metabolic capabilities for poorly characterized (anaerobic) microorganisms. We demonstrate this approach for the beneficial human gut microbe Faecalibacterium prausnitzii strain A2-165. We generated an automated draft reconstruction, which we curated against the limited biochemical data. This reconstruction modeling was used to develop in silico and in vitro a chemically defined medium (CDM), which was validated experimentally. Subsequent metabolomic analysis of the spent medium for growth on CDM was performed. We refined our metabolic reconstruction according to in vitro observed metabolite consumption and secretion and propose improvements to the current genome annotation of F. prausnitzii A2-165. We then used the reconstruction to systematically characterize its metabolic properties. Novel carbon source utilization capabilities and inabilities were predicted based on metabolic modeling and validated experimentally. This study resulted in a functional metabolic map of F. prausnitzii, which is available for further applications. The presented workflow can be readily extended to other poorly characterized and uncharacterized organisms to yield novel biochemical insights about the target organism. PMID:25002542

  20. Functional metabolic map of Faecalibacterium prausnitzii, a beneficial human gut microbe.

    PubMed

    Heinken, Almut; Khan, M Tanweer; Paglia, Giuseppe; Rodionov, Dmitry A; Harmsen, Hermie J M; Thiele, Ines

    2014-09-01

    The human gut microbiota plays a central role in human well-being and disease. In this study, we present an integrated, iterative approach of computational modeling, in vitro experiments, metabolomics, and genomic analysis to accelerate the identification of metabolic capabilities for poorly characterized (anaerobic) microorganisms. We demonstrate this approach for the beneficial human gut microbe Faecalibacterium prausnitzii strain A2-165. We generated an automated draft reconstruction, which we curated against the limited biochemical data. This reconstruction modeling was used to develop in silico and in vitro a chemically defined medium (CDM), which was validated experimentally. Subsequent metabolomic analysis of the spent medium for growth on CDM was performed. We refined our metabolic reconstruction according to in vitro observed metabolite consumption and secretion and propose improvements to the current genome annotation of F. prausnitzii A2-165. We then used the reconstruction to systematically characterize its metabolic properties. Novel carbon source utilization capabilities and inabilities were predicted based on metabolic modeling and validated experimentally. This study resulted in a functional metabolic map of F. prausnitzii, which is available for further applications. The presented workflow can be readily extended to other poorly characterized and uncharacterized organisms to yield novel biochemical insights about the target organism.

  1. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans123

    PubMed Central

    Jumpertz, Reiner; Le, Duc Son; Turnbaugh, Peter J; Trinidad, Cathy; Bogardus, Clifton; Gordon, Jeffrey I; Krakoff, Jonathan

    2011-01-01

    Background: Studies in mice indicate that the gut microbiome influences both sides of the energy-balance equation by contributing to nutrient absorption and regulating host genes that affect adiposity. However, it remains uncertain as to what extent gut microbiota are an important regulator of nutrient absorption in humans. Objective: With the use of a carefully monitored inpatient study cohort, we tested how gut bacterial community structure is affected by altering the nutrient load in lean and obese individuals and whether their microbiota are correlated with the efficiency of dietary energy harvest. Design: We investigated dynamic changes of gut microbiota during diets that varied in caloric content (2400 compared with 3400 kcal/d) by pyrosequencing bacterial 16S ribosomal RNA (rRNA) genes present in the feces of 12 lean and 9 obese individuals and by measuring ingested and stool calories with the use of bomb calorimetry. Results: The alteration of the nutrient load induced rapid changes in the gut microbiota. These changes were directly correlated with stool energy loss in lean individuals such that a 20% increase in Firmicutes and a corresponding decrease in Bacteroidetes were associated with an increased energy harvest of ≈150 kcal. A high degree of overfeeding in lean individuals was accompanied by a greater fractional decrease in stool energy loss. Conclusions: These results show that the nutrient load is a key variable that can influence the gut (fecal) bacterial community structure over short time scales. Furthermore, the observed associations between gut microbes and nutrient absorption indicate a possible role of the human gut microbiota in the regulation of the nutrient harvest. This trial was registered at clinicaltrials.gov as NCT00414063. PMID:21543530

  2. Helicobacter pylori Eradication Causes Perturbation of the Human Gut Microbiome in Young Adults

    PubMed Central

    Yap, Theresa Wan-Chen; Gan, Han-Ming; Lee, Yin-Peng; Leow, Alex Hwong-Ruey; Azmi, Ahmad Najib; Francois, Fritz; Perez-Perez, Guillermo I.; Loke, Mun-Fai; Goh, Khean-Lee; Vadivelu, Jamuna

    2016-01-01

    Background Accumulating evidence shows that Helicobacter pylori protects against some metabolic and immunological diseases in which the development of these diseases coincide with temporal or permanent dysbiosis. The aim of this study was to assess the effect of H. pylori eradication on the human gut microbiome. Methods As part of the currently on-going ESSAY (Eradication Study in Stable Adults/Youths) study, we collected stool samples from 17 H. pylori-positive young adult (18–30 years-old) volunteers. The same cohort was followed up 6, 12 and 18 months-post H. pylori eradication. The impact of H. pylori on the human gut microbiome pre- and post-eradication was investigated using high throughput 16S rRNA gene (V3-V4 region) sequencing using the Illumina Miseq followed by data analysis using Qiime pipeline. Results We compared the composition and diversity of bacterial communities in the fecal microbiome of the H. pylori-positive volunteers, before and after H. pylori eradication therapy. The 16S rRNA gene was sequenced at an average of 150,000–170,000 reads/sample. The microbial diversity were similar pre- and post-H. pylori eradication with no significant differences in richness and evenness of bacterial species. Despite that the general profile of the gut microbiome was similar pre- and post-eradication, some changes in the bacterial communities at the phylum and genus levels were notable, particularly the decrease in relative abundance of Bacterioidetes and corresponding increase in Firmicutes after H. pylori eradication. The significant increase of short-chain fatty acids (SCFA)-producing bacteria genera could also be associated with increased risk of metabolic disorders. Conclusions Our preliminary stool metagenomics study shows that eradication of H. pylori caused perturbation of the gut microbiome and may indirectly affect the health of human. Clinicians should be aware of the effect of broad spectrum antibiotics used in H. pylori eradication regimen

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

    PubMed Central

    Rey, Federico E.; Gonzalez, Mark D.; Cheng, Jiye; 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 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. PMID:23898195

  4. Symbiotic Human Gut Bacteria with Variable Metabolic Priorities for Host Mucosal Glycans

    PubMed Central

    Pudlo, Nicholas A.; Urs, Karthik; Kumar, Supriya Suresh; German, J. Bruce; Mills, David A.

    2015-01-01

    ABSTRACT Many symbiotic gut bacteria possess the ability to degrade multiple polysaccharides, thereby providing nutritional advantages to their hosts. Like microorganisms adapted to other complex nutrient environments, gut symbionts give different metabolic priorities to substrates present in mixtures. We investigated the responses of Bacteroides thetaiotaomicron, a common human intestinal bacterium that metabolizes more than a dozen different polysaccharides, including the O-linked glycans that are abundant in secreted mucin. Experiments in which mucin glycans were presented simultaneously with other carbohydrates show that degradation of these host carbohydrates is consistently repressed in the presence of alternative substrates, even by B. thetaiotaomicron previously acclimated to growth in pure mucin glycans. Experiments with media containing systematically varied carbohydrate cues and genetic mutants reveal that transcriptional repression of genes involved in mucin glycan metabolism is imposed by simple sugars and, in one example that was tested, is mediated through a small intergenic region in a transcript-autonomous fashion. Repression of mucin glycan-responsive gene clusters in two other human gut bacteria, Bacteroides massiliensis and Bacteroides fragilis, exhibited variable and sometimes reciprocal responses compared to those of B. thetaiotaomicron, revealing that these symbionts vary in their preference for mucin glycans and that these differences occur at the level of controlling individual gene clusters. Our results reveal that sensing and metabolic triaging of glycans are complex processes that vary among species, underscoring the idea that these phenomena are likely to be hidden drivers of microbiota community dynamics and may dictate which microorganisms preferentially commit to various niches in a constantly changing nutritional environment. PMID:26556271

  5. Vegetable microbiomes: is there a connection among opportunistic infections, human health and our 'gut feeling'?

    PubMed

    Berg, Gabriele; Erlacher, Armin; Smalla, Kornelia; Krause, Robert

    2014-11-01

    The highly diverse microbiomes of vegetables are reservoirs for opportunistic and emerging pathogens. In recent years, an increased consumption, larger scale production and more efficient distribution of vegetables together with an increased number of immunocompromised individuals resulted in an enhanced number of documented outbreaks of human infections associated with the consumption of vegetables. Here we discuss the occurrence of potential pathogens in vegetable microbiomes, the impact of farming and processing practices, and plant and human health issues. Based on these results, we discuss the question if vegetables can serve as a source of infection for immunocompromised individuals as well as possible solutions to avoid outbreaks. Moreover, the potentially positive aspects of the vegetables microbiome for the gut microbiota and human health are presented.

  6. The Gut Bacteria-Driven Obesity Development.

    PubMed

    Compare, Debora; Rocco, Alba; Sanduzzi Zamparelli, Marco; Nardone, Gerardo

    2016-01-01

    It is now well established that a healthy gut flora is largely responsible for the overall health of the host, while a perturbation in gut microbial communities can contribute to disease susceptibility. Obesity is a complex process involving genetic and environmental factors with an epidemiological burden that makes it a major public health issue. Studies of germ-free or gnotobiotic mice provided evidence that the diversity, as well as the presence and relative proportion of different microbes in the gut play active roles in energy homeostasis. Similarly, human studies showed that both the diversity of the microbiota and the Bacteroidetes/Firmicutes ratio are decreased in obese individuals. The 'obese microbiota' seems to be able to increase dietary energy harvest and favor weight gain and fat deposition. Although research in this field has just started and many of the available data are still conflicting, the results are providing exciting perspectives, and gut microbiota manipulation has already become a new target for both prevention and treatment of obesity. PMID:27028448

  7. Composition of the gut microbiota modulates the severity of malaria.

    PubMed

    Villarino, Nicolas F; LeCleir, Gary R; Denny, Joshua E; Dearth, Stephen P; Harding, Christopher L; Sloan, Sarah S; Gribble, Jennifer L; Campagna, Shawn R; Wilhelm, Steven W; Schmidt, Nathan W

    2016-02-23

    Plasmodium infections result in clinical presentations that range from asymptomatic to severe malaria, resulting in ∼1 million deaths annually. Despite this toll on humanity, the factors that determine disease severity remain poorly understood. Here, we show that the gut microbiota of mice influences the pathogenesis of malaria. Genetically similar mice from different commercial vendors, which exhibited differences in their gut bacterial community, had significant differences in parasite burden and mortality after infection with multiple Plasmodium species. Germfree mice that received cecal content transplants from "resistant" or "susceptible" mice had low and high parasite burdens, respectively, demonstrating the gut microbiota shaped the severity of malaria. Among differences in the gut flora were increased abundances of Lactobacillus and Bifidobacterium in resistant mice. Susceptible mice treated with antibiotics followed by yogurt made from these bacterial genera displayed a decreased parasite burden. Consistent with differences in parasite burden, resistant mice exhibited an elevated humoral immune response compared with susceptible mice. Collectively, these results identify the composition of the gut microbiota as a previously unidentified risk factor for severe malaria and modulation of the gut microbiota (e.g., probiotics) as a potential treatment to decrease parasite burden.

  8. Composition of the gut microbiota modulates the severity of malaria

    PubMed Central

    Villarino, Nicolas F.; LeCleir, Gary R.; Denny, Joshua E.; Dearth, Stephen P.; Harding, Christopher L.; Sloan, Sarah S.; Gribble, Jennifer L.; Campagna, Shawn R.; Wilhelm, Steven W.; Schmidt, Nathan W.

    2016-01-01

    Plasmodium infections result in clinical presentations that range from asymptomatic to severe malaria, resulting in ∼1 million deaths annually. Despite this toll on humanity, the factors that determine disease severity remain poorly understood. Here, we show that the gut microbiota of mice influences the pathogenesis of malaria. Genetically similar mice from different commercial vendors, which exhibited differences in their gut bacterial community, had significant differences in parasite burden and mortality after infection with multiple Plasmodium species. Germfree mice that received cecal content transplants from “resistant” or “susceptible” mice had low and high parasite burdens, respectively, demonstrating the gut microbiota shaped the severity of malaria. Among differences in the gut flora were increased abundances of Lactobacillus and Bifidobacterium in resistant mice. Susceptible mice treated with antibiotics followed by yogurt made from these bacterial genera displayed a decreased parasite burden. Consistent with differences in parasite burden, resistant mice exhibited an elevated humoral immune response compared with susceptible mice. Collectively, these results identify the composition of the gut microbiota as a previously unidentified risk factor for severe malaria and modulation of the gut microbiota (e.g., probiotics) as a potential treatment to decrease parasite burden. PMID:26858424

  9. Crystal Structures of Apparent Saccharide Sensors from Histidine Kinase Receptors Prevalent in a Human Gut Symbiont

    PubMed Central

    Zhang, Zhen; Liu, Qun; Hendrickson, Wayne A.

    2014-01-01

    The adult human gut presents a complicated ecosystem where host-bacterium symbiosis plays an important role. Bacteroides thetaiotaomicron is a predominant member of the gut microflora, providing the human digestive tract with a large number of glycolytic enzymes. Expression of many of these enzymes appears to be controlled by histidine kinase receptors that are fused into unusual hybrid two-component systems that share homologous periplasmic sensor domains. These sensor domains belong to the third most populated (HK3) family based on a previous bioinformatics analysis of predicted histidine kinase sensors. Here, we present crystal structures of two sensor domains representative of the HK3 family. Each sensor is folded into three domains: two seven-bladed β-propeller domains and one β-sandwich domain. Both sensors form dimers in crystals and one sensor appears to be physiologically relevant. The folding characteristics in the individual domains, the domain organization, and the oligomeric architecture are all unique to the HK3 sensors. The sequence analysis of the HK3 sensors indicates that these sensors are shared among other signaling molecules, implying a combinatorial molecular evolution. PMID:24995510

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

    PubMed Central

    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

    2015-01-01

    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. PMID:26154892

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

    NASA Astrophysics Data System (ADS)

    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.

  12. Effect of Tulathromycin on Colonization Resistance, Antimicrobial Resistance, and Virulence of Human Gut Microbiota in Chemostats

    PubMed Central

    Hao, Haihong; Zhou, Shengxi; Cheng, Guyue; Dai, Menghong; Wang, Xu; Liu, Zhenli; Wang, Yulian; Yuan, Zonghui

    2016-01-01

    To evaluate microbiological safety of tulathromycin on human intestinal bacteria, tulathromycin (0, 0.1, 1, 10, and 100 μg/mL) was added into Chemostats. Before and after drug exposure, we monitored (1) population, SCFA products, antimicrobial resistance, and colonization resistance of gut microbiota, and (2) the antimicrobial resistance genes, transferability, virulent genes, pathogenicity of Enterococus faecalis. Results showed that low level of tulathromycin did not exhibit microbiological hazard on resistance selection and colonization resistance. However, high level of tulathromycin (10 and 100 μg/mL) may disturb colonization resistance of human gut microbiota and select antimicrobial resistant E. faecalis. Most of the selected resistant E. faecalis carried resistant gene of ermB, transferable element of Tn1545 and three virulence genes (esp, cylA, and ace). One of them (E. faecalis 143) was confirmed to have higher horizontal transfer risk and higher pathogenicity. The calculated no observable adverse effect concentration (NOAEC) and microbiological acceptable daily intake (mADI) in our study was 1 μg/mL and 14.66 μg/kg.bw/day, respectively. PMID:27092131

  13. Exploring gut microbes in human health and disease: Pushing the envelope

    PubMed Central

    Sun, Jun; Chang, Eugene B.

    2014-01-01

    Humans have coevolved with their microbes over thousands of years, but this relationship, is now being dramatically affected by shifts in the collective human microbiome resulting from changes in the environment and societal norms. Resulting perturbations of intestinal host-microbe interactions can lead to miscues and altered host responses that increase the risk of pathogenic processes and promote “western” disorders such as inflammatory bowel diseases, cancers, obesity, diabetes, autism, and asthma. Given the current challenges and limitations in gene therapy, approaches that can reshape the gut microbiome represent a reasonable strategy for restoring the balance between host and microbes. In this review and commentary, we highlight recent progress in our understanding of the intestinal microbiome in the context of health and diseases, focusing on mechanistic concepts that underlie the complex relationships between host and microbes. Despite these gains, many challenges lie ahead that make it difficult to close the gap between the basic sciences and clinical application. We will discuss the potential therapeutic strategies that can be used to manipulate the gut microbiota, recognizing that the promise of pharmabiotics (“bugs to drugs”) is unlikely to be completely fulfilled without a greater understanding of enteric microbiota and its impact on mammalian physiology. By leveraging the knowledge gained through these studies, we will be prepared to enter the era of personalized medicine where clinical inventions can be custom-tailored to individual patients to achieve better outcomes. PMID:25642449

  14. Expression of Human Paraoxonase 1 Decreases Superoxide Levels and Alters Bacterial Colonization in the Gut of Drosophila melanogaster

    PubMed Central

    Pezzulo, Alejandro A.; Hornick, Emma E.; Rector, Michael V.; Estin, Miriam; Reisetter, Anna C.; Taft, Peter J.; Butcher, Stephen C.; Carter, A. Brent; Manak, J. Robert; Stoltz, David A.; Zabner, Joseph

    2012-01-01

    Paraoxonases (PON) are a family of proteins (PON1, 2 and 3) with multiple enzymatic activities. PON1 interferes with homoserine lactone-mediated quorum sensing in bacteria and with reactive oxygen species (ROS) in humans and mice. PON1 gene mutations have been linked to multiple traits, including aging, and diseases of the cardiovascular, nervous and gastrointestinal system. The overlapping enzymatic activities in the PON family members and high linkage disequilibrium rates within their polymorphisms confound animal and human studies of PON1 function. In contrast, arthropods such as Drosophila melanogaster have no PON homologs, resulting in an ideal model to study interactions between PON genotype and host phenotypes. We hypothesized that expression of PON1 in D. melanogaster would alter ROS. We found that PON1 alters expression of multiple oxidative stress genes and decreases superoxide anion levels in normal and germ-free D. melanogaster. We also found differences in the composition of the gut microbiota, with a remarkable increase in levels of Lactobacillus plantarum and associated changes in expression of antimicrobial and cuticle-related genes. PON1 expression directly decreased superoxide anion levels and altered bacterial colonization of the gut and its gene expression profile, highlighting the complex nature of the interaction between host genotype and gut microbiota. We speculate that the interaction between some genotypes and human diseases may be mediated by the presence of certain gut bacteria that can induce specific immune responses in the gut and other host tissues. PMID:22952763

  15. Phylogenetic distribution of three pathways for propionate production within the human gut microbiota

    PubMed Central

    Reichardt, Nicole; Duncan, Sylvia H; Young, Pauline; Belenguer, Alvaro; McWilliam Leitch, Carol; Scott, Karen P; Flint, Harry J; Louis, Petra

    2014-01-01

    Propionate is produced in the human large intestine by microbial fermentation and may help maintain human health. We have examined the distribution of three different pathways used by bacteria for propionate formation using genomic and metagenomic analysis of the human gut microbiota and by designing degenerate primer sets for the detection of diagnostic genes for these pathways. Degenerate primers for the acrylate pathway (detecting the lcdA gene, encoding lactoyl-CoA dehydratase) together with metagenomic mining revealed that this pathway is restricted to only a few human colonic species within the Lachnospiraceae and Negativicutes. The operation of this pathway for lactate utilisation in Coprococcus catus (Lachnospiraceae) was confirmed using stable isotope labelling. The propanediol pathway that processes deoxy sugars such as fucose and rhamnose was more abundant within the Lachnospiraceae (based on the pduP gene, which encodes propionaldehyde dehydrogenase), occurring in relatives of Ruminococcus obeum and in Roseburia inulinivorans. The dominant source of propionate from hexose sugars, however, was concluded to be the succinate pathway, as indicated by the widespread distribution of the mmdA gene that encodes methylmalonyl-CoA decarboxylase in the Bacteroidetes and in many Negativicutes. In general, the capacity to produce propionate or butyrate from hexose sugars resided in different species, although two species of Lachnospiraceae (C. catus and R. inulinivorans) are now known to be able to switch from butyrate to propionate production on different substrates. A better understanding of the microbial ecology of short-chain fatty acid formation may allow modulation of propionate formation by the human gut microbiota. PMID:24553467

  16. Higher Prevalence and Abundance of Bdellovibrio bacteriovorus in the Human Gut of Healthy Subjects

    PubMed Central

    Iebba, Valerio; Santangelo, Floriana; Totino, Valentina; Nicoletti, Mauro; Gagliardi, Antonella; De Biase, Riccardo Valerio; Cucchiara, Salvatore; Nencioni, Lucia; Conte, Maria Pia; Schippa, Serena

    2013-01-01

    Introduction Members of the human intestinal microbiota are key players in maintaining human health. Alterations in the composition of gut microbial community (dysbiosis) have been linked with important human diseases. Understanding the underlying processes that control community structure, including the bacterial interactions within the microbiota itself, is essential. Bdellovibrio bacteriovorus is a gram-negative bacterium that preys other gram-negative species for survival, acting as a population-balancer. It was found in terrestrial/aquatic ecosystems, and in animal intestines, postulating its presence also in the human gut. Methods The present study was aimed to evaluate, by end-point PCR and qPCR, the presence of B. bacteriovorus in intestinal and faecal biopsy specimens from 92 paediatric healthy subjects and patients, suffering from Inflammatory Bowel Diseases (IBD), Celiac disease and Cystic fibrosis (CF). Results i) B. bacteriovorus was present and abundant only in healthy individuals, while it was heavily reduced in patients, as in the case of IBD and Celiac, while in CF patients and relative controls we observed comparable results; ii) B. bacteriovorus seemed to be mucosa-associated, because all IBD and Celiac biopsies (and related controls) were treated with mucus-removing agents, leaving only the mucosa-attached microflora; iii) B. bacteriovorus abundance was district-dependent, with a major preponderance in duodenum, and gradually decreasing up to rectum; iv) B. bacteriovorus levels significantly dropped in disease status, in duodenum and ileum. Conclusions Results obtained in this study could represent the first step for new therapeutic strategies aimed to restore a balance in the intestinal ecosystem, utilizing Bdellovibrio as a probiotic. PMID:23613881

  17. Time course production of urolithins from ellagic acid by human gut microbiota.

    PubMed

    García-Villalba, Rocío; Beltrán, David; Espín, Juan Carlos; Selma, María Victoria; Tomás-Barberán, Francisco A

    2013-09-18

    Ellagic acid (EA) is converted to urolithins by gut microbiota. Urolithins have beneficial biological effects in humans, but differences in urolithin production capacity among individuals have been shown. Therefore, the identification of the urolithin production pathways and the microorganisms implicated is of high interest. EA was incubated with gut microbiota from two volunteers able to produce urolithins but with different in vivo urolithin profiles (urolithin A and isourolithin A producers). The metabolic capabilities observed in vivo were retained in vitro. Both individuals showed a much higher abundance of Clostridium leptum group of Firmicutes phylum than Bacteroides / Prevotella . EA was either dissolved in DMSO or suspended in water. DMSO increased EA solubility but decreased urolithin production rate due to a delay in growth of some microbial groups, principally, Clostridium coccoides . This allowed the detection of catabolic intermediates [urolithins M-5, M-6, M-7, C, and 2,3,8,10-tetrahydroxy urolithin (urolithin E)]. Bacteria from C. coccoides group (or genera co-occurring in vivo with this group) seem to be involved in production of different urolithins.

  18. Transcriptional interactions suggest niche segregation among microorganisms in the human gut.

    PubMed

    Plichta, Damian Rafal; Juncker, Agnieszka Sierakowska; Bertalan, Marcelo; Rettedal, Elizabeth; Gautier, Laurent; Varela, Encarna; Manichanh, Chaysavanh; Fouqueray, Charlène; Levenez, Florence; Nielsen, Trine; Doré, Joël; Machado, Ana Manuel Dantas; de Evgrafov, Mari Cristina Rodriguez; Hansen, Torben; Jørgensen, Torben; Bork, Peer; Guarner, Francisco; Pedersen, Oluf; Sommer, Morten O A; Ehrlich, S Dusko; Sicheritz-Pontén, Thomas; Brunak, Søren; Nielsen, H Bjørn

    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 Europeans. In 102 significantly interacting species pairs, the transcriptional changes led to a reduced expression of orthologous functions between the coexisting species. Specific species-species transcriptional interactions were enriched for functions important for H2 and CO2 homeostasis, butyrate biosynthesis, ATP-binding cassette (ABC) transporters, flagella assembly and bacterial chemotaxis, as well as for the metabolism of carbohydrates, amino acids and cofactors. The analysis gives the first insight into the microbial community-wide transcriptional interactions, and suggests that the regulation of gene expression plays an important role in species adaptation to coexistence and that niche segregation takes place at the transcriptional level. PMID:27564131

  19. Identification and Phylogeny of the First T Cell Epitope Identified from a Human Gut Bacteroides Species.

    PubMed

    Perez-Muñoz, Maria Elisa; Joglekar, Payal; Shen, Yi-Ju; Shen, Yi-Ji; Chang, Kuan Y; Peterson, Daniel A

    2015-01-01

    Host T cell reactivity toward gut bacterial epitopes has been recognized as part of disease pathogenesis. However, the specificity of T cells that recognize this vast number of epitopes has not yet been well described. After colonizing a C57BL/6J germ-free mouse with the human gut symbiotic bacteria Bacteroides thetaiotaomicron, we isolated a T cell that recognized these bacteria in vitro. Using this T cell, we mapped the first known non-carbohydrate T cell epitope within the phylum Bacteroidetes. The T cell also reacted to two other additional Bacteroides species. We identified the peptide that stimulated the T cell by using a genetic approach. Genomic data from the epitope-positive and epitope-negative bacteria explain the cross-reactivity of the T cell to multiple species. This epitope degeneracy should shape our understanding of the T cell repertoire stimulated by the complex microbiome residing in the gastrointestinal tract in both healthy and disease states. PMID:26637014

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

    PubMed Central

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

    2013-01-01

    Summary 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. PMID:25343111

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

    PubMed

    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 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.

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

    PubMed Central

    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 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. PMID:23150581

  3. Progress and challenges in developing metabolic footprints from diet in human gut microbial cometabolism.

    PubMed

    Duffy, Linda C; Raiten, Daniel J; Hubbard, Van S; Starke-Reed, Pamela

    2015-05-01

    Homo sapiens harbor trillions of microbes, whose microbial metagenome (collective genome of a microbial community) using omic validation interrogation tools is estimated to be at least 100-fold that of human cells, which comprise 23,000 genes. This article highlights some of the current progress and open questions in nutrition-related areas of microbiome research. It also underscores the metabolic capabilities of microbial fermentation on nutritional substrates that require further mechanistic understanding and systems biology approaches of studying functional interactions between diet composition, gut microbiota, and host metabolism. Questions surrounding bacterial fermentation and degradation of dietary constituents (particularly by Firmicutes and Bacteroidetes) and deciphering how microbial encoding of enzymes and derived metabolites affect recovery of dietary energy by the host are more complex than previously thought. Moreover, it is essential to understand to what extent the intestinal microbiota is subject to dietary control and to integrate these data with functional metabolic signatures and biomarkers. Many lines of research have demonstrated the significant role of the gut microbiota in human physiology and disease. Probiotic and prebiotic products are proliferating in the market in response to consumer demand, and the science and technology around these products are progressing rapidly. With high-throughput molecular technologies driving the science, studying the bidirectional interactions of host-microbial cometabolism, epithelial cell maturation, shaping of innate immune development, normal vs. dysfunctional nutrient absorption and processing, and the complex signaling pathways involved is now possible. Substantiating the safety and mechanisms of action of probiotic/prebiotic formulations is critical. Beneficial modulation of the human microbiota by using these nutritional and biotherapeutic strategies holds considerable promise as next

  4. Progress and challenges in developing metabolic footprints from diet in human gut microbial cometabolism.

    PubMed

    Duffy, Linda C; Raiten, Daniel J; Hubbard, Van S; Starke-Reed, Pamela

    2015-05-01

    Homo sapiens harbor trillions of microbes, whose microbial metagenome (collective genome of a microbial community) using omic validation interrogation tools is estimated to be at least 100-fold that of human cells, which comprise 23,000 genes. This article highlights some of the current progress and open questions in nutrition-related areas of microbiome research. It also underscores the metabolic capabilities of microbial fermentation on nutritional substrates that require further mechanistic understanding and systems biology approaches of studying functional interactions between diet composition, gut microbiota, and host metabolism. Questions surrounding bacterial fermentation and degradation of dietary constituents (particularly by Firmicutes and Bacteroidetes) and deciphering how microbial encoding of enzymes and derived metabolites affect recovery of dietary energy by the host are more complex than previously thought. Moreover, it is essential to understand to what extent the intestinal microbiota is subject to dietary control and to integrate these data with functional metabolic signatures and biomarkers. Many lines of research have demonstrated the significant role of the gut microbiota in human physiology and disease. Probiotic and prebiotic products are proliferating in the market in response to consumer demand, and the science and technology around these products are progressing rapidly. With high-throughput molecular technologies driving the science, studying the bidirectional interactions of host-microbial cometabolism, epithelial cell maturation, shaping of innate immune development, normal vs. dysfunctional nutrient absorption and processing, and the complex signaling pathways involved is now possible. Substantiating the safety and mechanisms of action of probiotic/prebiotic formulations is critical. Beneficial modulation of the human microbiota by using these nutritional and biotherapeutic strategies holds considerable promise as next

  5. Bacterial flora as indicated by PCR-temperature gradient gel electrophoresis (TGGE) of 16S rDNA gene fragments from isolated guts of phlebotomine sand flies (Diptera: Psychodidae).

    PubMed

    Guernaoui, S; Garcia, D; Gazanion, E; Ouhdouch, Y; Boumezzough, A; Pesson, B; Fontenille, D; Sereno, D

    2011-03-01

    In this study, we tested the capacity of Temperature Gradient Gel Electrophoresis (TGGE)-based fingerprinting of 16S rDNA PCR fragments to assess bacterial composition in a single isolated sand fly gut. Bacterial content was studied in different life stages of a laboratory-reared colony of Phlebotomus duboscqi and in a wild-caught Phlebotomus papatasi population. Our study demonstrates that a major reorganization in the gut bacterial community occurs during metamorphosis of sand flies. Chloroflexi spp. was dominant in the guts of pre-imaginal stages, although Microbacterium spp. and another as yet unidentified bacteria were detected in the gut of the adult specimen. Interestingly, Microbacterium spp. was also found in all the adult guts of both species. We demonstrate that the analysis of bacterial diversity in an individualized sand fly gut is possible with fingerprinting of 16S rDNA. The use of such methodology, in conjunction with other culture-based methods, will be of great help in investigating the behavior of the Leishmania-bacterial community in an ecological context.

  6. The Gut Microbiota in Immune-Mediated Inflammatory Diseases.

    PubMed

    Forbes, Jessica D; Van Domselaar, Gary; Bernstein, Charles N

    2016-01-01

    The collection of microbes and their genes that exist within and on the human body, collectively known as the microbiome has emerged as a principal factor in human health and disease. Humans and microbes have established a symbiotic association over time, and perturbations in this association have been linked to several immune-mediated inflammatory diseases (IMID) including inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. IMID is a term used to describe a group of chronic, highly disabling diseases that affect different organ systems. Though a cornerstone commonality between IMID is the idiopathic nature of disease, a considerable portion of their pathobiology overlaps including epidemiological co-occurrence, genetic susceptibility loci and environmental risk factors. At present, it is clear that persons with an IMID are at an increased risk for developing comorbidities, including additional IMID. Advancements in sequencing technologies and a parallel explosion of 16S rDNA and metagenomics community profiling studies have allowed for the characterization of microbiomes throughout the human body including the gut, in a myriad of human diseases and in health. The main challenge now is to determine if alterations of gut flora are common between IMID or, if particular changes in the gut community are in fact specific to a single disease. Herein, we review and discuss the relationships between the gut microbiota and IMID. PMID:27462309

  7. The Gut Microbiota in Immune-Mediated Inflammatory Diseases

    PubMed Central

    Forbes, Jessica D.; Van Domselaar, Gary; Bernstein, Charles N.

    2016-01-01

    The collection of microbes and their genes that exist within and on the human body, collectively known as the microbiome has emerged as a principal factor in human health and disease. Humans and microbes have established a symbiotic association over time, and perturbations in this association have been linked to several immune-mediated inflammatory diseases (IMID) including inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. IMID is a term used to describe a group of chronic, highly disabling diseases that affect different organ systems. Though a cornerstone commonality between IMID is the idiopathic nature of disease, a considerable portion of their pathobiology overlaps including epidemiological co-occurrence, genetic susceptibility loci and environmental risk factors. At present, it is clear that persons with an IMID are at an increased risk for developing comorbidities, including additional IMID. Advancements in sequencing technologies and a parallel explosion of 16S rDNA and metagenomics community profiling studies have allowed for the characterization of microbiomes throughout the human body including the gut, in a myriad of human diseases and in health. The main challenge now is to determine if alterations of gut flora are common between IMID or, if particular changes in the gut community are in fact specific to a single disease. Herein, we review and discuss the relationships between the gut microbiota and IMID. PMID:27462309

  8. Gut microbiota and obesity.

    PubMed

    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. PMID:26459447

  9. Gut microbiota and obesity.

    PubMed

    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.

  10. Gut microbiota and hepatic encephalopathy.

    PubMed

    Dhiman, Radha K

    2013-06-01

    There is a strong relationship between liver and gut; while the portal venous system receives blood from the gut, and its contents may affect liver functions, liver in turn, affects intestinal functions through bile secretion. There is robust evidence that the pathogenesis of hepatic encephalopathy (HE) is linked to alterations in gut microbiota and their by-products such as ammonia, indoles, oxindoles, endotoxins, etc. In the setting of intestinal barrier and immune dysfunction, these by-products are involved in the pathogenesis of complications of liver cirrhosis including HE and systemic inflammation plays an important role. Prebiotics, probiotics and synbiotics may exhibit efficacy in the treatment of HE by modulating the gut flora. They improve derangement in flora by decreasing the counts of pathogenic bacteria and thus improving the endotoxemia, HE and the liver disease. Current evidence suggest that the trials evaluating the role of probiotics in the treatment of HE are of not high quality and all trials had high risk of bias and high risk of random errors. Therefore, the use of probiotics for patients with HE cannot be currently recommended. Further RCTs are required. This review summarizes the main literature findings about the relationships between gut flora and HE, both in terms of the pathogenesis and the treatment of HE.

  11. Mining the human gut microbiota for effector strains that shape the immune system.

    PubMed

    Ahern, Philip P; Faith, Jeremiah J; Gordon, Jeffrey I

    2014-06-19

    The gut microbiota codevelops with the immune system beginning at birth. Mining the microbiota for bacterial strains responsible for shaping the structure and dynamic operations of the innate and adaptive arms of the immune system represents a formidable combinatorial problem but one that needs to be overcome to advance mechanistic understanding of microbial community and immune system coregulation and to develop new diagnostic and therapeutic approaches that promote health. Here, we discuss a scalable, less biased approach for identifying effector strains in complex microbial communities that impact immune function. The approach begins by identifying uncultured human fecal microbiota samples that transmit immune phenotypes to germ-free mice. Clonally arrayed sequenced collections of bacterial strains are constructed from representative donor microbiota. If the collection transmits phenotypes, effector strains are identified by testing randomly generated subsets with overlapping membership in individually housed germ-free animals. Detailed mechanistic studies of effector strain-host interactions can then be performed. PMID:24950201

  12. Risungbinella massiliensis sp. nov., a new member of Thermoactinomycetaceae isolated from human gut.

    PubMed

    Dubourg, Grégory; Lagier, Jean-Christophe; Robert, Catherine; Armstrong, Nicholas; Couderc, Carine; Fournier, Pierre-Edouard; Raoult, Didier

    2016-06-01

    A novel filamentous bacterium, designated GD1(T), was isolated from the gut microbiota of a 38-year-old male who suffered from a Coxiella burnetii vascular for which he received multiple a broad-spectrum antibiotic cocktail at the time of the stool collection. The strain was isolated as a part of culturomics study by cultivation on 5 % sheep blood agar in aerobic condition at 28 °C, after 14 days of incubation. Strain GD1(T) shows 16S rRNA gene sequence similarities of 98.01 % to the type strain of Risungbinella pyongyangensis. We describe here the features of this bacterium, together with the complete genome sequence and annotation. The G+C content of the genomic DNA was determined to be 40.1 mol %. The major fatty acids of strain GD1(T) were identified as iso-C15:0, iso-C17:0, anteiso-C15:0, iso-C14:0 and C16:0. The 3,440,191 bp long genome contains 3540 protein-coding and 67 RNA genes, including three rRNA genes. Strain GD1(T) (= DSM 46691 = CSUR P1082) sp. nov. is here classified as the type strain of a new species, Risungbinella massiliensis, within the family Thermoactinomycetaceae. To date, strain GD1(T) is the first member of the family Thermoactinomycetaceae isolated from human gut and the fourth from a human specimen. PMID:26984352

  13. Production of α-Galactosylceramide by a Prominent Member of the Human Gut Microbiota

    PubMed Central

    Kashyap, Purna C.; Williams, Brianna B.; Clardy, Jon; Kronenberg, Mitchell; Sonnenburg, Justin L.; Comstock, Laurie E.; Bluestone, Jeffrey A.; Fischbach, Michael A.

    2013-01-01

    While the human gut microbiota are suspected to produce diffusible small molecules that modulate host signaling pathways, few of these molecules have been identified. Species of Bacteroides and their relatives, which often comprise >50% of the gut community, are unusual among bacteria in that their membrane is rich in sphingolipids, a class of signaling molecules that play a key role in inducing apoptosis and modulating the host immune response. Although known for more than three decades, the full repertoire of Bacteroides sphingolipids has not been defined. Here, we use a combination of genetics and chemistry to identify the sphingolipids produced by Bacteroides fragilis NCTC 9343. We constructed a deletion mutant of BF2461, a putative serine palmitoyltransferase whose yeast homolog catalyzes the committed step in sphingolipid biosynthesis. We show that the Δ2461 mutant is sphingolipid deficient, enabling us to purify and solve the structures of three alkaline-stable lipids present in the wild-type strain but absent from the mutant. The first compound was the known sphingolipid ceramide phosphorylethanolamine, and the second was its corresponding dihydroceramide base. Unexpectedly, the third compound was the glycosphingolipid α-galactosylceramide (α-GalCerBf), which is structurally related to a sponge-derived sphingolipid (α-GalCer, KRN7000) that is the prototypical agonist of CD1d-restricted natural killer T (iNKT) cells. We demonstrate that α-GalCerBf has similar immunological properties to KRN7000: it binds to CD1d and activates both mouse and human iNKT cells both in vitro and in vivo. Thus, our study reveals BF2461 as the first known member of the Bacteroides sphingolipid pathway, and it indicates that the committed steps of the Bacteroides and eukaryotic sphingolipid pathways are identical. Moreover, our data suggest that some Bacteroides sphingolipids might influence host immune homeostasis. PMID:23874157

  14. Ranking the impact of human health disorders on gut metabolism: systemic lupus erythematosus and obesity as study cases.

    PubMed

    Rojo, David; Hevia, Arancha; Bargiela, Rafael; López, Patricia; Cuervo, Adriana; González, Sonia; Suárez, Ana; Sánchez, Borja; Martínez-Martínez, Mónica; Milani, Christian; Ventura, Marco; Barbas, Coral; Moya, Andrés; Suárez, Antonio; Margolles, Abelardo; Ferrer, Manuel

    2015-02-06

    Multiple factors have been shown to alter intestinal microbial diversity. It remains to be seen, however, how multiple collective pressures impact the activity in the gut environment and which, if any, is positioned as a dominant driving factor determining the final metabolic outcomes. Here, we describe the results of a metabolome-wide scan of gut microbiota in 18 subjects with systemic lupus erythematosus (SLE) and 17 healthy control subjects and demonstrate a statistically significant difference (p < 0.05) between the two groups. Healthy controls could be categorized (p < 0.05) based on their body mass index (BMI), whereas individuals with SLE could not. We discuss the prevalence of SLE compared with BMI as the dominant factor that regulates gastrointestinal microbial metabolism and provide plausible explanatory causes. Our results uncover novel perspectives with clinical relevance for human biology. In particular, we rank the importance of various pathophysiologies for gut homeostasis.

  15. Nuclear translocation of NF-κB in intact human gut tissue upon stimulation with coffee and roasting products.

    PubMed

    Sauer, Tanja; Raithel, Martin; Kressel, Jürgen; Muscat, Sonja; Münch, Gerald; Pischetsrieder, Monika

    2011-09-01

    In the healthy gut, NF-κB is a critical factor of the intestinal immune system, whereas inflammatory bowel diseases are associated with chronic activation of NF-κB. Previous studies indicated that coffee induces nuclear translocation of NF-κB in macrophages, an effect attributed to roasting products. In the present work, coffee extract or roasting products induced nuclear translocation of NF-κB in macrophages, Caco-2 cells, and primary human intestinal microvascular endothelial cells (up to fivefold, p<0.001). Since the effect clearly depended on the cell type, ex vivo experiments were performed with intact human gut tissue from biopsies. The uniformity of the specimens and tissue viability during ex vivo incubation for up to 2 h were verified. Roasting products led to a concentration dependent significant increase of nuclear translocation of NF-κB in human gut tissue (up to 2.85 fold increase, p=0.0321), whereas coffee extract induced a trend towards higher nuclear NF-κB concentration. NF-κB activation in macrophages and Caco-2 cells by roasting products was significantly blocked by co-incubation with catalase (p=0.011 and p=0.024) indicating involvement of H(2)O(2)-signaling. Monitoring of extracellular H(2)O(2) indicated that roasting products in coffee constantly generate H(2)O(2) by spontaneous oxygen reduction, which is only partially detoxified by cellular antioxidative systems. Thus, it can be concluded that ex vivo stimulation of intact human gut tissue is a valuable model to study nutritional effects on complex tissue systems. Furthermore, the consumption of coffee and roasting products may be able to induce nuclear NF-κB translocation in the human gut.

  16. Resource conflict and cooperation between human host and gut microbiota: implications for nutrition and health.

    PubMed

    Wasielewski, Helen; Alcock, Joe; Aktipis, Athena

    2016-05-01

    Diet has been known to play an important role in human health since at least the time period of the ancient Greek physician Hippocrates. In the last decade, research has revealed that microorganisms inhabiting the digestive tract, known as the gut microbiota, are critical factors in human health. This paper draws on concepts of cooperation and conflict from ecology and evolutionary biology to make predictions about host-microbiota interactions involving nutrients. To optimally extract energy from some resources (e.g., fiber), hosts require cooperation from microbes. Other nutrients can be utilized by both hosts and microbes (e.g., simple sugars, iron) in their ingested form, which may lead to greater conflict over these resources. This framework predicts that some negative health effects of foods are driven by the direct effects of these foods on human physiology and by indirect effects resulting from microbiome-host competition and conflict (e.g., increased invasiveness and inflammation). Similarly, beneficial effects of some foods on host health may be enhanced by resource sharing and other cooperative behaviors between host and microbes that may downregulate inflammation and virulence. Given that some foods cultivate cooperation between hosts and microbes while others agitate conflict, host-microbe interactions may be novel targets for interventions aimed at improving nutrition and human health.

  17. Resource conflict and cooperation between human host and gut microbiota: implications for nutrition and health.

    PubMed

    Wasielewski, Helen; Alcock, Joe; Aktipis, Athena

    2016-05-01

    Diet has been known to play an important role in human health since at least the time period of the ancient Greek physician Hippocrates. In the last decade, research has revealed that microorganisms inhabiting the digestive tract, known as the gut microbiota, are critical factors in human health. This paper draws on concepts of cooperation and conflict from ecology and evolutionary biology to make predictions about host-microbiota interactions involving nutrients. To optimally extract energy from some resources (e.g., fiber), hosts require cooperation from microbes. Other nutrients can be utilized by both hosts and microbes (e.g., simple sugars, iron) in their ingested form, which may lead to greater conflict over these resources. This framework predicts that some negative health effects of foods are driven by the direct effects of these foods on human physiology and by indirect effects resulting from microbiome-host competition and conflict (e.g., increased invasiveness and inflammation). Similarly, beneficial effects of some foods on host health may be enhanced by resource sharing and other cooperative behaviors between host and microbes that may downregulate inflammation and virulence. Given that some foods cultivate cooperation between hosts and microbes while others agitate conflict, host-microbe interactions may be novel targets for interventions aimed at improving nutrition and human health. PMID:27270755

  18. Characterization of functional properties of Enterococcus faecium strains isolated from human gut.

    PubMed

    İspirli, Hümeyra; Demirbaş, Fatmanur; Dertli, Enes

    2015-11-01

    The aim of this work was to characterize the functional properties of Enterococcus faecium strains identified after isolation from human faeces. Of these isolates, strain R13 showed the best resistance to low pH, bile salts, and survival in the simulated in vitro digestion assay, and demonstrated an important level of adhesion to hexadecane as a potential probiotic candidate. Analysis of the antibiotic resistance of E. faecium strains indicated that in general these isolates were sensitive to the tested antibiotics and no strain appeared to be resistant to vancomycin. Examination of the virulence determinants for E. faecium strains demonstrated that all strains contained the virulence genes common in gut- and food-originated enterococci, and strain R13 harboured the lowest number of virulence genes. Additionally, no strain contained the genes related to cytolysin metabolism and showed hemolytic activity. The antimicrobial role of E. faecium strains was tested against several pathogens, in which different levels of inhibitory effects were observed, and strain R13 was inhibitory to all tested pathogens. PCR screening of genes encoding enterocin A and B indicated the presence of these genes in E. faecium strains. Preliminary characterization of bacteriocins revealed that their activity was lost after proteolytic enzyme treatments, but no alteration in antimicrobial activity was observed at different pHs (3.5 to 9.5) and after heat treatments. In conclusion, this study revealed the functional characteristics of E. faecium R13 as a gut isolate, and this strain could be developed as a new probiotic after further tests.

  19. Pan-genome of the dominant human gut-associated archaeon, Methanobrevibacter smithii, studied in twins

    PubMed Central

    Hansen, Elizabeth E.; Lozupone, Catherine A.; Rey, Federico E.; Guruge, Janaki L.; Narra, Aneesha; Goodfellow, Jonathan; Zaneveld, Jesse R.; McDonald, Daniel T.; Goodrich, Julia A.; Heath, Andrew C.; Knight, Rob; Gordon, Jeffrey I.

    2011-01-01

    The human gut microbiota harbors three main groups of H2-consuming microbes: methanogens including the dominant archaeon, Methanobrevibacter smithii, a polyphyletic group of acetogens, and sulfate-reducing bacteria. Defining their roles in the gut is important for understanding how hydrogen metabolism affects the efficiency of fermentation of dietary components. We quantified methanogens in fecal samples from 40 healthy adult female monozygotic (MZ) and 28 dizygotic (DZ) twin pairs, analyzed bacterial 16S rRNA datasets generated from their fecal samples to identify taxa that co-occur with methanogens, sequenced the genomes of 20 M. smithii strains isolated from families of MZ and DZ twins, and performed RNA-Seq of a subset of strains to identify their responses to varied formate concentrations. The concordance rate for methanogen carriage was significantly higher for MZ versus DZ twin pairs. Co-occurrence analysis revealed 22 bacterial species-level taxa positively correlated with methanogens: all but two were members of the Clostridiales, with several being, or related to, known hydrogen-producing and -consuming bacteria. The M. smithii pan-genome contains 987 genes conserved in all strains, and 1,860 variably represented genes. Strains from MZ and DZ twin pairs had a similar degree of shared genes and SNPs, and were significantly more similar than strains isolated from mothers or members of other families. The 101 adhesin-like proteins (ALPs) in the pan-genome (45 ± 6 per strain) exhibit strain-specific differences in expression and responsiveness to formate. We hypothesize that M. smithii strains use their different repertoires of ALPs to create diversity in their metabolic niches, by allowing them to establish syntrophic relationships with bacterial partners with differing metabolic capabilities and patterns of co-occurrence. PMID:21317366

  20. The Rebirth of Culture in Microbiology through the Example of Culturomics To Study Human Gut Microbiota

    PubMed Central

    Lagier, Jean-Christophe; Hugon, Perrine; Khelaifia, Saber; Fournier, Pierre-Edouard; La Scola, Bernard

    2015-01-01

    SUMMARY Bacterial culture was the first method used to describe the human microbiota, but this method is considered outdated by many researchers. Metagenomics studies have since been applied to clinical microbiology; however, a “dark matter” of prokaryotes, which corresponds to a hole in our knowledge and includes minority bacterial populations, is not elucidated by these studies. By replicating the natural environment, environmental microbiologists were the first to reduce the “great plate count anomaly,” which corresponds to the difference between microscopic and culture counts. The revolution in bacterial identification also allowed rapid progress. 16S rRNA bacterial identification allowed the accurate identification of new species. Mass spectrometry allowed the high-throughput identification of rare species and the detection of new species. By using these methods and by increasing the number of culture conditions, culturomics allowed the extension of the known human gut repertoire to levels equivalent to those of pyrosequencing. Finally, taxonogenomics strategies became an emerging method for describing new species, associating the genome sequence of the bacteria systematically. We provide a comprehensive review on these topics, demonstrating that both empirical and hypothesis-driven approaches will enable a rapid increase in the identification of the human prokaryote repertoire. PMID:25567229

  1. The rebirth of culture in microbiology through the example of culturomics to study human gut microbiota.

    PubMed

    Lagier, Jean-Christophe; Hugon, Perrine; Khelaifia, Saber; Fournier, Pierre-Edouard; La Scola, Bernard; Raoult, Didier

    2015-01-01

    Bacterial culture was the first method used to describe the human microbiota, but this method is considered outdated by many researchers. Metagenomics studies have since been applied to clinical microbiology; however, a "dark matter" of prokaryotes, which corresponds to a hole in our knowledge and includes minority bacterial populations, is not elucidated by these studies. By replicating the natural environment, environmental microbiologists were the first to reduce the "great plate count anomaly," which corresponds to the difference between microscopic and culture counts. The revolution in bacterial identification also allowed rapid progress. 16S rRNA bacterial identification allowed the accurate identification of new species. Mass spectrometry allowed the high-throughput identification of rare species and the detection of new species. By using these methods and by increasing the number of culture conditions, culturomics allowed the extension of the known human gut repertoire to levels equivalent to those of pyrosequencing. Finally, taxonogenomics strategies became an emerging method for describing new species, associating the genome sequence of the bacteria systematically. We provide a comprehensive review on these topics, demonstrating that both empirical and hypothesis-driven approaches will enable a rapid increase in the identification of the human prokaryote repertoire.

  2. Variations in the Post-weaning Human Gut Metagenome Profile As Result of Bifidobacterium Acquisition in the Western Microbiome.

    PubMed

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

    2016-01-01

    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.

  3. Variations in the Post-weaning Human Gut Metagenome Profile As Result of Bifidobacterium Acquisition in the Western Microbiome

    PubMed Central

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

    2016-01-01

    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. PMID:27462302

  4. Variations in the Post-weaning Human Gut Metagenome Profile As Result of Bifidobacterium Acquisition in the Western Microbiome.

    PubMed

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

    2016-01-01

    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. PMID:27462302

  5. The Gut Microbiota and Human Health with an Emphasis on the Use of Microencapsulated Bacterial Cells

    PubMed Central

    Prakash, Satya; Tomaro-Duchesneau, Catherine; Saha, Shyamali; Cantor, Arielle

    2011-01-01

    The gut microbiota plays a crucial role in maintaining health. Alterations of the gut bacterial population have been associated with a number of diseases. Past and recent studies suggest that one can positively modify the contents of the gut microbiota by introducing prebiotics, probiotics, synbiotics, and other therapeutics. This paper focuses on probiotic modulation of the gut microbiota by their delivery to the lower gastrointestinal tract (GIT). There are numerous obstacles to overcome before microorganisms can be utilized as therapeutics. One important limitation is the delivery of viable cells to the lower GIT without a significant loss of cell viability and metabolic features through the harsh conditions of the upper GIT. Microencapsulation has been shown to overcome this, with various types of microcapsules available for resolving this limitation. This paper discusses the gut microbiota and its role in disease, with a focus on microencapsulated probiotics and their potentials and limitations. PMID:21772792

  6. Is there a role for human pluripotent stem cells in modelling interstitial cells of Cajal and gut motility disorders?

    PubMed

    Meng, Wenbo; Zhou, Jerry; Elliott, Ross; Murphy, Patricia; Ho, Vincent; O'Connor, Michael

    2015-01-01

    Gastrointestinal motility disorders affect millions of people worldwide, resulting in significant morbidity and mortality. Current treatments for these disorders are inadequate and often provide little to no relief for patients. As a result, gastrointestinal motility disorders produce substantial long-term social and economic burdens in both developed and developing countries. These limited treatment options arise largely from our relatively poor understanding of the molecular etiology for the majority of gastrointestinal motility disorders. In turn, this is due to our limited access to normal or diseased human gut tissue for use in research. In particular while the interstitial cells of Cajal (ICC) are known to be important for gastrointestinal motility, little is known of how these cells function or how they are involved in disease initiation and progression. The advent of human pluripotent stem cell technology offers an opportunity to generate large amounts of human tissue for both research and clinical applications. The application of this technology to gastrointestinal motility disorders is currently only in its infancy and as yet no studies have described ICC production from human pluripotent cells. By considering the present understanding of the anatomical, cellular and molecular basis of gut motility with particular emphasis on ICC, this review provides a clear framework for the application of human pluripotent stem cell technology to answer fundamental questions of ICC involvement in gut motility. PMID:25391378

  7. Isolation and molecular characterization of methicillin-resistant coagulase-negative staphylococci from nasal flora of healthy humans at three community institutions in Rio de Janeiro City.

    PubMed

    Silva, F R; Mattos, E M; Coimbra, M V; Ferreira-Carvalho, B T; Figueiredo, A M

    2001-08-01

    We describe the isolation and molecular characterization of methicillin-resistant coagulase-negative staphylococci (MRCNS) from the nasal flora of healthy humans from three institutions located in Rio de Janeiro City. Swabs were obtained from the nares of students attending a non-residential public school and adults from two military quarters. Isolates of staphylococci were tested for the presence of the mecA gene by hybridization with a specific probe. S. epidermidis was the most frequent MRCNS (38 of the total 45 CNS isolated). Twenty-five percent of nasal staphylococcal carriers studied were colonized with MRCNS. Pulsed-field gel electrophoresis (PFGE) of SmaI-digested genomic DNA was carried out to study the clonality of the methicillin-resistant S. epidermidis (MRSE) isolates. In addition to cross-colonization among individuals belonging to the same institution, familial cross-colonization appeared to contribute to the spread of the methicillin-resistant isolates among two inter-communicable institutions. Indeed, the wide genomic diversity among the MRSE flora suggests that the spread of the mecA gene among these isolates might also have occurred via horizontal transmission. Despite the limited number of institutions analysed, it is reasonable to conclude that our data do not represent a situation unique to the three organizations but may reflect other communities in Rio with respect to transmission of MRCNS. PMID:11561975

  8. Holding a grudge: persisting anti-phage CRISPR immunity in multiple human gut microbiomes.

    PubMed

    Mick, Eran; Stern, Adi; Sorek, Rotem

    2013-05-01

    The CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR-associated) system of bacteria and archaea constitutes a mechanism of acquired adaptive immunity against phages, which is based on genome-encoded markers of previously infecting phage sequences ("spacers"). As a repository of phage sequences, these spacers make the system particularly suitable for elucidating phage-bacteria interactions in metagenomic studies. Recent metagenomic analyses of CRISPRs associated with the human microbiome intriguingly revealed conserved "memory spacers" shared by bacteria in multiple unrelated, geographically separated individuals. Here, we discuss possible avenues for explaining this phenomenon by integrating insights from CRISPR biology and phage-bacteria ecology, with a special focus on the human gut. We further explore the growing body of evidence for the role of CRISPR/Cas in regulating the interplay between bacteria and lysogenic phages, which may be intimately related to the presence of memory spacers and sheds new light on the multifaceted biological and ecological modes of action of CRISPR/Cas. PMID:23439321

  9. Bifidobacteria and Their Role as Members of the Human Gut Microbiota.

    PubMed

    O'Callaghan, Amy; van Sinderen, Douwe

    2016-01-01

    Members of the genus Bifidobacterium are among the first microbes to colonize the human gastrointestinal tract and are believed to exert positive health benefits on their host. Due to their purported health-promoting properties, bifidobacteria have been incorporated into many functional foods as active ingredients. Bifidobacteria naturally occur in a range of ecological niches that are either directly or indirectly connected to the animal gastrointestinal tract, such as the human oral cavity, the insect gut and sewage. To be able to survive in these particular ecological niches, bifidobacteria must possess specific adaptations to be competitive. Determination of genome sequences has revealed genetic attributes that may explain bifidobacterial ecological fitness, such as metabolic abilities, evasion of the host adaptive immune system and colonization of the host through specific appendages. However, genetic modification is crucial toward fully elucidating the mechanisms by which bifidobacteria exert their adaptive abilities and beneficial properties. In this review we provide an up to date summary of the general features of bifidobacteria, whilst paying particular attention to the metabolic abilities of this species. We also describe methods that have allowed successful genetic manipulation of bifidobacteria. PMID:27379055

  10. A human volunteer study to assess the impact of confectionery sweeteners on the gut microbiota composition.

    PubMed

    Beards, Emma; Tuohy, Kieran; Gibson, Glenn

    2010-09-01

    Sweeteners are being sourced to lower the energetic value of confectionery including chocolates. Some, especially non-digestible carbohydrates, may possess other benefits for human health upon their fermentation by the colonic microbiota. The present study assessed non-digestible carbohydrate sweeteners, selected for use in low-energy chocolates, for their ability to beneficially modulate faecal bacterial profiles in human volunteers. Forty volunteers consumed a test chocolate (low-energy or experimental chocolate) containing 22.8 g of maltitol (MTL), MTL and polydextrose (PDX), or MTL and resistant starch for fourteen consecutive days. The dose of the test chocolates was doubled every 2 weeks over a 6-week period. Numbers of faecal bifidobacteria significantly increased with all the three test treatments. Chocolate containing the PDX blend also significantly increased faecal lactobacilli (P = 0.00 001) after the 6 weeks. The PDX blend also showed significant increases in faecal propionate and butyrate (P = 0.002 and 0.006, respectively). All the test chocolates were well tolerated with no significant change in bowel habit or intestinal symptoms even at a daily dose of 45.6 g of non-digestible carbohydrate sweetener. This is of importance not only for giving manufacturers a sugar replacement that can reduce energetic content, but also for providing a well-tolerated means of delivering high levels of non-digestible carbohydrates into the colon, bringing about improvements in the biomarkers of gut health.

  11. Extensive personal human gut microbiota culture collections characterized and manipulated in gnotobiotic mice

    PubMed Central

    Goodman, Andrew L.; Kallstrom, George; Faith, Jeremiah J.; Reyes, Alejandro; Moore, Aimee; Dantas, Gautam; Gordon, Jeffrey I.

    2011-01-01

    The proportion of the human gut bacterial community that is recalcitrant to culture remains poorly defined. In this report, we combine high-throughput anaerobic culturing techniques with gnotobiotic animal husbandry and metagenomics to show that the human fecal microbiota consists largely of taxa and predicted functions that are represented in its readily cultured members. When transplanted into gnotobiotic mice, complete and cultured communities exhibit similar colonization dynamics, biogeographical distribution, and responses to dietary perturbations. Moreover, gnotobiotic mice can be used to shape these personalized culture collections to enrich for taxa suited to specific diets. We also demonstrate that thousands of isolates from a single donor can be clonally archived and taxonomically mapped in multiwell format to create personalized microbiota collections. Retrieving components of a microbiota that have coexisted in single donors who have physiologic or disease phenotypes of interest and reuniting them in various combinations in gnotobiotic mice should facilitate preclinical studies designed to determine the degree to which tractable bacterial taxa are able to transmit donor traits or influence host biology. PMID:21436049

  12. Characterisation of inorganic microparticles in pigment cells of human gut associated lymphoid tissue.

    PubMed Central

    Powell, J J; Ainley, C C; Harvey, R S; Mason, I M; Kendall, M D; Sankey, E A; Dhillon, A P; Thompson, R P

    1996-01-01

    Macrophages at the base of human gut associated lymphoid tissue (GALT), become loaded early in life with dark granular pigment that is rich in aluminium, silicon, and titanium. The molecular characteristics, intracellular distribution, and source of this pigment is described. Laser scanning and electron microscopy showed that pigmented macrophages were often closely related to collagen fibres and plasma cells in GALT of both small and large intestine and contained numerous phagolysosomes, previously described as granules, that are rich in electron dense submicron sized particles. Morphological assessment, x ray microanalysis, and image electron energy loss spectroscopy showed three distinct types of microparticle: type I - spheres of titanium dioxide, 100-200 nm diameter, characterised as the synthetic food-additive polymorph anatase; type II - aluminosilicates, < 100-400 nm in length, generally of flaky appearance, often with adsorbed surface iron, and mostly characteristic of the natural clay mineral kaolinite; and type III - mixed environmental silicates without aluminium, 100-700 nm in length and of variable morphology. Thus, this cellular pigment that is partly derived from food additives and partly from the environment is composed of inert inorganic microparticles and loaded into phagolysosomes of macrophages within the GALT of all human subjects. These observations suggest that the pathogenicity of this pigment should be further investigated since, in susceptible individuals, the same intracellular distribution of these three types of submicron particle causes chronic latent granulomatous inflammation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 7 PMID:8675092

  13. Effect of oligosaccharides on the adhesion of gut bacteria to human HT-29 cells.

    PubMed

    Altamimi, M; Abdelhay, O; Rastall, R A

    2016-06-01

    The influence of five oligosaccharides (cellobiose, stachyose, raffinose, lactulose and chito-oligosaccharides) on the adhesion of eight gut bacteria (Bifidobacterium bifidum ATCC 29521, Bacteroides thetaiotaomicron ATCC 29148D-5, Clostridium leptum ATCC 29065, Blautia coccoides ATCC 29236, Faecalibacterium prausnitzii ATCC 27766, Bacteroides fragilis ATCC 23745, Clostridium difficile ATCC 43255 and Lactobacillus casei ATCC 393) to mucous secreting and non-mucous secreting HT-29 human epithelial cells, was investigated. In pure culture, the bacteria showed variations in their ability to adhere to epithelial cells. The effect of oligosaccharides diminished adhesion and the presence of mucus played a major factor in adhesion, likely due to high adhesiveness to mucins present in the native human mucus layer covering the whole cell surface. However, clostridia displayed almost the same level of adhesion either with or without mucus being present. Bl. coccoides adhesion was decreased by stachyose and cellobiose in non-mucus-secreting cells in pure culture, while in mixed faecal culture cellobiose displayed the highest antiadhesive activity with an overall average of 65% inhibition amongst tested oligomers and lactulose displayed the lowest with an average of 47.4%. Bifidobacteria, Bacteroides, lactobacilli and clostridia were inhibited within the following ranges 47-78%, 32-65%, 11.7-58% and 64-85% respectively. This means that clostridia were the most strongly influenced members of the microflora amongst the bacterial groups tested in mixed culture. In conclusion, introducing oligosaccharides which are candidate prebiotics into pure or mixed cultures has affected bacterial adhesion. PMID:27018325

  14. Bifidobacteria and Their Role as Members of the Human Gut Microbiota

    PubMed Central

    O'Callaghan, Amy; van Sinderen, Douwe

    2016-01-01

    Members of the genus Bifidobacterium are among the first microbes to colonize the human gastrointestinal tract and are believed to exert positive health benefits on their host. Due to their purported health-promoting properties, bifidobacteria have been incorporated into many functional foods as active ingredients. Bifidobacteria naturally occur in a range of ecological niches that are either directly or indirectly connected to the animal gastrointestinal tract, such as the human oral cavity, the insect gut and sewage. To be able to survive in these particular ecological niches, bifidobacteria must possess specific adaptations to be competitive. Determination of genome sequences has revealed genetic attributes that may explain bifidobacterial ecological fitness, such as metabolic abilities, evasion of the host adaptive immune system and colonization of the host through specific appendages. However, genetic modification is crucial toward fully elucidating the mechanisms by which bifidobacteria exert their adaptive abilities and beneficial properties. In this review we provide an up to date summary of the general features of bifidobacteria, whilst paying particular attention to the metabolic abilities of this species. We also describe methods that have allowed successful genetic manipulation of bifidobacteria. PMID:27379055

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

    PubMed

    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 (P< 0·05). Increasing the consumption of almonds or pistachios appears to be an effective means of modifying gut microbiota composition.

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

    PubMed

    Hunt, G J; Young, A K; Bonfield, R A

    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 (f1 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 f1 were derived with the aid of literature data for excretion following intravenous administration of technetium-95 m as pertechnetate, and gave averaged data for f1 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. PMID:11281526

  17. Development and Validation of a Microarray for the Investigation of the CAZymes Encoded by the Human Gut Microbiome

    PubMed Central

    Leroy, Quentin; Vialettes, Bernard; Million, Matthieu; Raoult, Didier; Henrissat, Bernard

    2013-01-01

    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. PMID:24391873

  18. Predicting Drug Extraction in the Human Gut Wall: Assessing Contributions from Drug Metabolizing Enzymes and Transporter Proteins using Preclinical Models.

    PubMed

    Peters, Sheila Annie; Jones, Christopher R; Ungell, Anna-Lena; Hatley, Oliver J D

    2016-06-01

    Intestinal metabolism can limit oral bioavailability of drugs and increase the risk of drug interactions. It is therefore important to be able to predict and quantify it in drug discovery and early development. In recent years, a plethora of models-in vivo, in situ and in vitro-have been discussed in the literature. The primary objective of this review is to summarize the current knowledge in the quantitative prediction of gut-wall metabolism. As well as discussing the successes of current models for intestinal metabolism, the challenges in the establishment of good preclinical models are highlighted, including species differences in the isoforms; regional abundances and activities of drug metabolizing enzymes; the interplay of enzyme-transporter proteins; and lack of knowledge on enzyme abundances and availability of empirical scaling factors. Due to its broad specificity and high abundance in the intestine, CYP3A is the enzyme that is frequently implicated in human gut metabolism and is therefore the major focus of this review. A strategy to assess the impact of gut wall metabolism on oral bioavailability during drug discovery and early development phases is presented. Current gaps in the mechanistic understanding and the prediction of gut metabolism are highlighted, with suggestions on how they can be overcome in the future.

  19. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip

    PubMed Central

    Kim, Hyun Jung; Li, Hu; Collins, James J.; Ingber, Donald E.

    2016-01-01

    A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria. By ceasing peristalsis-like motions while maintaining luminal flow, lack of epithelial deformation was shown to trigger bacterial overgrowth similar to that observed in patients with ileus and inflammatory bowel disease. Analysis of intestinal inflammation on-chip revealed that immune cells and lipopolysaccharide endotoxin together stimulate epithelial cells to produce four proinflammatory cytokines (IL-8, IL-6, IL-1β, and TNF-α) that are necessary and sufficient to induce villus injury and compromise intestinal barrier function. Thus, this human gut-on-a-chip can be used to analyze contributions of microbiome to intestinal pathophysiology and dissect disease mechanisms in a controlled manner that is not possible using existing in vitro systems or animal models. PMID:26668389

  20. The human gut microbiome as a screening tool for colorectal cancer.

    PubMed

    Zackular, Joseph P; Rogers, Mary A M; Ruffin, Mack T; Schloss, Patrick D

    2014-11-01

    Recent studies have suggested that the gut microbiome may be an important factor in the development of colorectal cancer. Abnormalities in the gut microbiome have been reported in patients with colorectal cancer; however, this microbial community has not been explored as a potential screen for early-stage disease. We characterized the gut microbiome in patients from three clinical groups representing the stages of colorectal cancer development: healthy, adenoma, and carcinoma. Analysis of the gut microbiome from stool samples revealed both an enrichment and depletion of several bacterial populations associated with adenomas and carcinomas. Combined with known clinical risk factors of colorectal cancer (e.g., BMI, age, race), data from the gut microbiome significantly improved the ability to differentiate between healthy, adenoma, and carcinoma clinical groups relative to risk factors alone. Using Bayesian methods, we determined that using gut microbiome data as a screening tool improved the pretest to posttest probability of adenoma more than 50-fold. For example, the pretest probability in a 65-year-old was 0.17% and, after using the microbiome data, this increased to 10.67% (1 in 9 chance of having an adenoma). Taken together, the results of our study demonstrate the feasibility of using the composition of the gut microbiome to detect the presence of precancerous and cancerous lesions. Furthermore, these results support the need for more cross-sectional studies with diverse populations and linkage to other stool markers, dietary data, and personal health information.

  1. Phytate degradation by human gut isolated Bifidobacterium pseudocatenulatum ATCC27919 and its probiotic potential.

    PubMed

    Haros, Monika; Carlsson, Nils-Gunnar; Almgren, Annette; Larsson-Alminger, Marie; Sandberg, Ann-Sofie; Andlid, Thomas

    2009-09-30

    The growing awareness of the relationship between diet and health has led to an increasing demand for food products that support health above and beyond providing basic nutrition. Probiotics are live organisms present in foods, which yield health benefits related to their interactions with the gastrointestinal tract. Phytases are a subgroup of phosphatases that catalyse the desphosphorylation of phytate, which reduces its negative impact on mineral bioavailability, and generates lower inositol phosphates. The aims of this investigation were to (i) study the ability of the probiotic candidate Bifidobacterium pseudocatenulatum to degrade phytate in synthetic medium, to (ii) identify the lower inositol phosphates generated, to (iii) study its survival under conditions mimicking gastrointestinal passage and finally to (iv) assess adhesion of the bacteria to Caco-2 cells. The first steps of InsP(6) degradation by B. pseudocatenulatum phytate-degrading enzyme/s were preferentially initiated at the DL-6-position and 5-position of the myo-inositol ring. It suggests that the main InsP(6) degradation pathway by B. pseudocatenulatum by sequential removal of phosphate groups was D/L-Ins(1,2,3,4,5)P(5) or D/L-Ins(1,2,3,4,6)P(5); D/L-Ins(1,2,3,4)P(4); to finally Ins(1,2,3)P(3) and D/L-Ins(1,2,4)P(3)/D/L-Ins(1,3,4)P(3). This human strain also showed a notable tolerance to bile as well as a selective adhesion capacity (adhesion to control surfaces was zero), to human intestinal Caco-2 cells comparable to the commercial probiotic B. lactis. The phytate-degrading activity constitutes a novel metabolic trait which could contribute to the improvement of mineral absorption in the intestine as a nutritional probiotic feature with potential trophic effect in human gut. PMID:19674804

  2. The Human Gut Microbiome as a Transporter of Antibiotic Resistance Genes between Continents

    PubMed Central

    Bengtsson-Palme, Johan; Angelin, Martin; Huss, Mikael; Kjellqvist, Sanela; Kristiansson, Erik; Palmgren, Helena; Larsson, D. G. Joakim

    2015-01-01

    Previous studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in Central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL)-producing enterobacteria, and the isolates obtained were genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable before and after travel, but there was an increasing abundance of Proteobacteria in 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7-fold), and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producing Escherichia coli, while none returning from Africa were positive. Despite deep sequencing efforts, the sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics. PMID:26259788

  3. Meta-analyses of human gut microbes associated with obesity and IBD

    PubMed Central

    Walters, William A.; Xu, Zech; Knight, Rob

    2016-01-01

    Recent studies have linked human gut microbes to obesity and inflammatory bowel disease, but consistent signals have been difficult to identify. Here we test for indicator taxa and general features of the microbiota that are generally consistent across studies of obesity and of IBD, focusing on studies involving high-throughput sequencing of the 16S rRNA gene (which we could process using a common computational pipeline). We find that IBD has a consistent signature across studies and allows high classification accuracy of IBD from non-IBD subjects, but that although subjects can be classified as lean or obese within each individual study with statistically significant accuracy, consistent with the ability of the microbiota to experimentally transfer this phenotype, signatures of obesity are not consistent between studies even when the data are analyzed with consistent methods. The results suggest that correlations between microbes and clinical conditions with different effect sizes (e.g. the large effect size of IBD versus the small effect size of obesity) may require different cohort selection and analysis strategies. PMID:25307765

  4. Differential Metabolism of Exopolysaccharides from Probiotic Lactobacilli by the Human Gut Symbiont Bacteroides thetaiotaomicron.

    PubMed

    Lammerts van Bueren, Alicia; Saraf, Aakanksha; Martens, Eric C; Dijkhuizen, Lubbert

    2015-06-15

    Probiotic microorganisms are ingested as food or supplements and impart positive health benefits to consumers. Previous studies have indicated that probiotics transiently reside in the gastrointestinal tract and, in addition to modulating commensal species diversity, increase the expression of genes for carbohydrate metabolism in resident commensal bacterial species. In this study, it is demonstrated that the human gut commensal species Bacteroides thetaiotaomicron efficiently metabolizes fructan exopolysaccharide (EPS) synthesized by probiotic Lactobacillus reuteri strain 121 while only partially degrading reuteran and isomalto/malto-polysaccharide (IMMP) α-glucan EPS polymers. B. thetaiotaomicron metabolized these EPS molecules via the activation of enzymes and transport systems encoded by dedicated polysaccharide utilization loci specific for β-fructans and α-glucans. Reduced metabolism of reuteran and IMMP α-glucan EPS molecules may be due to reduced substrate binding by components of the starch utilization system (sus). This study reveals that microbial EPS substrates activate genes for carbohydrate metabolism in B. thetaiotaomicron and suggests that microbially derived carbohydrates provide a carbohydrate-rich reservoir for B. thetaiotaomicron nutrient acquisition in the gastrointestinal tract. PMID:25841008

  5. Genomic Analysis of the Human Gut Microbiome Suggests Novel Enzymes Involved in Quinone Biosynthesis

    PubMed Central

    Ravcheev, Dmitry A.; Thiele, Ines

    2016-01-01

    Ubiquinone and menaquinone are membrane lipid-soluble carriers of electrons that are essential for cellular respiration. Eukaryotic cells can synthesize ubiquinone but not menaquinone, whereas prokaryotes can synthesize both quinones. So far, most of the human gut microbiome (HGM) studies have been based on metagenomic analysis. Here, we applied an analysis of individual HGM genomes to the identification of ubiquinone and menaquinone biosynthetic pathways. In our opinion, the shift from metagenomics to analysis of individual genomes is a pivotal milestone in investigation of bacterial communities, including the HGM. The key results of this study are as follows. (i) The distribution of the canonical pathways in the HGM genomes was consistent with previous reports and with the distribution of the quinone-dependent reductases for electron acceptors. (ii) The comparative genomics analysis identified four alternative forms of the previously known enzymes for quinone biosynthesis. (iii) Genes for the previously unknown part of the futalosine pathway were identified, and the corresponding biochemical reactions were proposed. We discuss the remaining gaps in the menaquinone and ubiquinone pathways in some of the microbes, which indicate the existence of further alternate genes or routes. Together, these findings provide further insight into the biosynthesis of quinones in bacteria and the physiology of the HGM. PMID:26904004

  6. Mining the human gut microbiota for effector strains that shape the immune system

    PubMed Central

    Ahern, Philip P.; Faith, Jeremiah J.; Gordon, Jeffrey I.

    2014-01-01

    Summary The gut microbiota co-develops with the immune system beginning at birth. Mining the microbiota for bacterial strains responsible for shaping the structure and dynamic operations of the innate and adaptive arms of the immune system represents a formidable combinatorial problem but one that needs to be overcome to advance mechanistic understanding of microbial community-immune system co-regulation, and in order to develop new diagnostic and therapeutic approaches that promote health. Here, we discuss a scalable, less biased approach for identifying effector strains in complex microbial communities that impact immune function. The approach begins by identifying uncultured human fecal microbiota samples that transmit immune phenotypes to germ-free mice. Clonally-arrayed sequenced collections of bacterial strains are constructed from representative donor microbiota. If the collection transmits phenotypes, effector strains are identified by testing randomly generated subsets with overlapping membership in individually-housed germ-free animals. Detailed mechanistic studies of effector strain-host interactions can then be performed. PMID:24950201

  7. Composition and Metabolic Activities of Bacterial Biofilms Colonizing Food Residues in the Human Gut

    PubMed Central

    Macfarlane, Sandra; Macfarlane, George T.

    2006-01-01

    Bacteria growing in the human large intestine live in intimate association with the host and play an important role in host digestive processes, gut physiology, and metabolism. Fecal bacteria have been investigated extensively, but few studies have been done on biofilms that form on digestive wastes in the large bowel. The aims of this investigation were to investigate the composition and metabolic activities of bacterial communities that colonize the surfaces of food residues in fecal material, with respect to their role in the fermentation of complex carbohydrates. Fresh stools were obtained from 15 healthy donors, and food residues were separated by filtration. Adherent bacteria were removed by surfactant treatment for microbiological analysis and fermentation studies. Scanning electron microscopy and fluorescent in situ hybridization in conjunction with confocal laser scanning microscopy (CLSM) were used to visualize intact biofilms. Results showed that bacterial populations strongly adhering to particulate matter were phenotypically similar in composition to unattached communities, with bacteroides and bifidobacteria predominating. Biofilms comprised a mixture of living and dead bacteria, and CLSM showed that bifidobacteria in the biofilms occurred as isolated dispersed cells and in microcolonies near the interface with the substratum. Fermentation experiments with a variety of complex carbohydrates demonstrated that biofilm populations were more efficient in digesting polysaccharides, while nonadhering communities fermented oligosaccharides most rapidly. Acetate was the principal fermentation product formed by biofilm bacteria, whereas higher levels of butyrate were produced by nonadherent populations, showing that the two communities were metabolically distinct. PMID:16957247

  8. Differential Metabolism of Exopolysaccharides from Probiotic Lactobacilli by the Human Gut Symbiont Bacteroides thetaiotaomicron

    PubMed Central

    Saraf, Aakanksha; Martens, Eric C.; Dijkhuizen, Lubbert

    2015-01-01

    Probiotic microorganisms are ingested as food or supplements and impart positive health benefits to consumers. Previous studies have indicated that probiotics transiently reside in the gastrointestinal tract and, in addition to modulating commensal species diversity, increase the expression of genes for carbohydrate metabolism in resident commensal bacterial species. In this study, it is demonstrated that the human gut commensal species Bacteroides thetaiotaomicron efficiently metabolizes fructan exopolysaccharide (EPS) synthesized by probiotic Lactobacillus reuteri strain 121 while only partially degrading reuteran and isomalto/malto-polysaccharide (IMMP) α-glucan EPS polymers. B. thetaiotaomicron metabolized these EPS molecules via the activation of enzymes and transport systems encoded by dedicated polysaccharide utilization loci specific for β-fructans and α-glucans. Reduced metabolism of reuteran and IMMP α-glucan EPS molecules may be due to reduced substrate binding by components of the starch utilization system (sus). This study reveals that microbial EPS substrates activate genes for carbohydrate metabolism in B. thetaiotaomicron and suggests that microbially derived carbohydrates provide a carbohydrate-rich reservoir for B. thetaiotaomicron nutrient acquisition in the gastrointestinal tract. PMID:25841008

  9. The Human Gut Microbiome as a Transporter of Antibiotic Resistance Genes between Continents.

    PubMed

    Bengtsson-Palme, Johan; Angelin, Martin; Huss, Mikael; Kjellqvist, Sanela; Kristiansson, Erik; Palmgren, Helena; Larsson, D G Joakim; Johansson, Anders

    2015-10-01

    Previous studies of antibiotic resistance dissemination by travel have, by targeting only a select number of cultivable bacterial species, omitted most of the human microbiome. Here, we used explorative shotgun metagenomic sequencing to address the abundance of >300 antibiotic resistance genes in fecal specimens from 35 Swedish students taken before and after exchange programs on the Indian peninsula or in Central Africa. All specimens were additionally cultured for extended-spectrum beta-lactamase (ESBL)-producing enterobacteria, and the isolates obtained were genome sequenced. The overall taxonomic diversity and composition of the gut microbiome remained stable before and after travel, but there was an increasing abundance of Proteobacteria in 25/35 students. The relative abundance of antibiotic resistance genes increased, most prominently for genes encoding resistance to sulfonamide (2.6-fold increase), trimethoprim (7.7-fold), and beta-lactams (2.6-fold). Importantly, the increase observed occurred without any antibiotic intake. Of 18 students visiting the Indian peninsula, 12 acquired ESBL-producing Escherichia coli, while none returning from Africa were positive. Despite deep sequencing efforts, the sensitivity of metagenomics was not sufficient to detect acquisition of the low-abundant genes responsible for the observed ESBL phenotype. In conclusion, metagenomic sequencing of the intestinal microbiome of Swedish students returning from exchange programs in Central Africa or the Indian peninsula showed increased abundance of genes encoding resistance to widely used antibiotics.

  10. "Lachnoclostridium bouchesdurhonense," a new bacterial species isolated from human gut microbiota.

    PubMed

    Amadou, T; Hosny, M; La Scola, B; Cassir, N

    2016-09-01

    We report the main characteristics of "Lachnoclostridium bouchesdurhonense" strain AT5(T) (=CSUR P2181), a new bacterial species isolated from the gut microbiota of an obese patient from Marseille. PMID:27493758

  11. 'Lachnoclostridium massiliosenegalense', a new bacterial species isolated from the human gut microbiota.

    PubMed

    Tidjani Alou, M; Lagier, J-C; La Scola, B; Cassir, N

    2016-11-01

    We report the main characteristics of 'Lachnoclostridium massiliosenegalense' strain mt23(T) (=CSUR P299 =DSM 102084), a new bacterial species isolated from the gut microbiota of a healthy young girl from Senegal. PMID:27595004

  12. 'Lachnoclostridium massiliosenegalense', a new bacterial species isolated from the human gut microbiota.

    PubMed

    Tidjani Alou, M; Lagier, J-C; La Scola, B; Cassir, N

    2016-11-01

    We report the main characteristics of 'Lachnoclostridium massiliosenegalense' strain mt23(T) (=CSUR P299 =DSM 102084), a new bacterial species isolated from the gut microbiota of a healthy young girl from Senegal.

  13. Arsenic Metabolism by Human Gut Microbiota upon in Vitro Digestion of Contaminated Soils

    EPA Science Inventory

    Speciation analysis is essential when evaluating risks from, arsenic (As) exposure. In an oral exposure scenario, the importance of presystemic metabolism by gut microorganisms has been evidenced with in vivo animal models and in vitro experiments with animal microbiota. Howeve...

  14. [Metabolic therapy at the edge between human hosts and gut microbes].

    PubMed

    Blasco-Baque, V; Serino, M; Burcelin, R

    2013-01-01

    Personalized medicine is becoming day-after-day more urgent taking into account the great diversity characterizing patients affected by a given pathology, especially metabolic diseases. In fact, antidiabetic/obesity treatments have shown a reduced or no effect at all in some patients, representing a major challenge physicians have to face worldwide. Therefore, efforts have to be put to identify individual factors affecting our susceptibility towards a given medication. In that regard, gut microbiota may stand for the missing piece of the metabolic puzzle regulating host response, since its role in the induction of metabolic diseases has now been achieved. In fact, we firstly provided a bacterial explanation for the low-grade chronic inflammation featuring metabolic diseases, by showing the lipopolysaccharide as a trigger and risk factor of such pathologies. However, despite similar lineages of microbes characterize the gut of people, important differences still remain, which may be responsible for opposite effect of treatments such as pre- or probiotics, whose efficacy seems to be governed by the own gut microbiota of subjects. We have recently shown that gut microbiota is associated to the inclination to resist or not high-fat diet-induced type 2 diabetes in mice. In addition, the direct targeting of gut microbes by dietary fibers reversed the observed metabolic phenotype. These results, together with the literature, strongly suggest gut microbiota as a new target for the development of personalized metabolic therapy. PMID:23348854

  15. Molecular Dissection of Xyloglucan Recognition in a Prominent Human Gut Symbiont

    PubMed Central

    Tauzin, Alexandra S.; Kwiatkowski, Kurt J.; Orlovsky, Nicole I.; Smith, Christopher J.; Creagh, A. Louise; Haynes, Charles A.; Wawrzak, Zdzislaw

    2016-01-01

    ABSTRACT Polysaccharide utilization loci (PUL) within the genomes of resident human gut Bacteroidetes are central to the metabolism of the otherwise indigestible complex carbohydrates known as “dietary fiber.” However, functional characterization of PUL lags significantly behind sequencing efforts, which limits physiological understanding of the human-bacterial symbiosis. In particular, the molecular basis of complex polysaccharide recognition, an essential prerequisite to hydrolysis by cell surface glycosidases and subsequent metabolism, is generally poorly understood. Here, we present the biochemical, structural, and reverse genetic characterization of two unique cell surface glycan-binding proteins (SGBPs) encoded by a xyloglucan utilization locus (XyGUL) from Bacteroides ovatus, which are integral to growth on this key dietary vegetable polysaccharide. Biochemical analysis reveals that these outer membrane-anchored proteins are in fact exquisitely specific for the highly branched xyloglucan (XyG) polysaccharide. The crystal structure of SGBP-A, a SusD homolog, with a bound XyG tetradecasaccharide reveals an extended carbohydrate-binding platform that primarily relies on recognition of the β-glucan backbone. The unique, tetra-modular structure of SGBP-B is comprised of tandem Ig-like folds, with XyG binding mediated at the distal C-terminal domain. Despite displaying similar affinities for XyG, reverse-genetic analysis reveals that SGBP-B is only required for the efficient capture of smaller oligosaccharides, whereas the presence of SGBP-A is more critical than its carbohydrate-binding ability for growth on XyG. Together, these data demonstrate that SGBP-A and SGBP-B play complementary, specialized roles in carbohydrate capture by B. ovatus and elaborate a model of how vegetable xyloglucans are accessed by the Bacteroidetes. PMID:27118585

  16. Spontaneous secretion of interferon γ and interleukin 4 by human intraepithelial and lamina propria gut lymphocytes

    PubMed Central

    Carol, M; Lambrechts, A; Van Gossum, A; Libin, M; Goldman, M; Mascart-Lemone, F

    1998-01-01

    Background—Cytokines secreted by intestinal T lymphocytes probably play a critical role in regulation of the gut associated immune responses. 
Aims—To quantify interferon γ (IFN-γ) and interleukin 4 (IL-4) secreting cells (SC) among human intraepithelial (IEL) and lamina propria (LPL) lymphocytes from the duodenum and right colon in non-pathological situations and in the absence of in vitro stimulation. 
Patients—Duodenal and right colonic biopsy specimens were obtained from patients with no inflammation of the intestinal mucosa. 
Methods—Intraepithelial and lamina propria cell suspensions were assayed for numbers of cells spontaneously secreting IFN-γ and IL-4 by a two site reverse enzyme linked immunospot technique (ELISPOT). 
Results—The relatively high proportion of duodenal lymphocytes spontaneously secreting IFN-γ (IEL 3.6%; LPL 1.9%) and IL-4 (IEL 1.3%; LPL 0.7%) contrasted with the very low numbers of spontaneously IFN-γ SC and the absence of spontaneously IL-4 SC among peripheral blood mononuclear cells. In the basal state, both IFN-γ and IL-4 were mainly produced by CD4+ cells. Within the colon, only 0.2% of IEL and LPL secreted IFN-γ in the basal state, and 0.1% secreted IL-4. 
Conclusions—Compared with peripheral lymphocytes substantial proportions of intestinal epithelial and lamina propria lymphocytes spontaneously secrete IFN-γ and/or IL-4. These cytokines are probably involved in the normal homoeostasis of the human intestinal mucosa. Disturbances in their secretion could play a role in the pathogenesis of gastrointestinal diseases. 

 Keywords: intestinal lymphocytes; ELISPOT; interferon γ; interleukin 4 PMID:9659157

  17. The Influence of Staphylococcus aureus on Gut Microbial Ecology in an In Vitro Continuous Culture Human Colonic Model System

    PubMed Central

    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). Furtheremore, 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. PMID:21858036

  18. The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes.

    PubMed

    Kostic, Aleksandar D; Gevers, Dirk; Siljander, Heli; Vatanen, Tommi; Hyötyläinen, Tuulia; Hämäläinen, Anu-Maaria; Peet, Aleksandr; Tillmann, Vallo; Pöhö, Päivi; Mattila, Ismo; Lähdesmäki, Harri; Franzosa, Eric A; Vaarala, Outi; de Goffau, Marcus; Harmsen, Hermie; Ilonen, Jorma; Virtanen, Suvi M; Clish, Clary B; Orešič, Matej; Huttenhower, Curtis; Knip, Mikael; Xavier, Ramnik J

    2015-02-11

    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 infants genetically predisposed to T1D. Modeling trajectories of microbial abundances through infancy revealed a subset of microbial relationships shared across most subjects. Although strain composition of a given species was highly variable between individuals, it was stable within individuals throughout infancy. Metabolic composition and metabolic pathway abundance remained constant across time. A marked drop in alpha-diversity was observed in T1D progressors in the time window between seroconversion and T1D diagnosis, accompanied by spikes in inflammation-favoring organisms, gene functions, and serum and stool metabolites. This work identifies trends in the development of the human infant gut microbiome along with specific alterations that precede T1D onset and distinguish T1D progressors from nonprogressors. PMID:25662751

  19. The Dynamics of the Human Infant Gut Microbiome in Development and in Progression towards Type 1 Diabetes

    PubMed Central

    Kostic, Aleksandar D.; Gevers, Dirk; Siljander, Heli; Vatanen, Tommi; Hyötyläinen, Tuulia; Hämäläinen, Anu-Maaria; Peet, Aleksandr; Tillmann, Vallo; Pöhö, Päivi; Mattila, Ismo; Lähdesmäki, Harri; Franzosa, Eric A.; Vaarala, Outi; de Goffau, Marcus; Harmsen, Hermie; Ilonen, Jorma; Virtanen, Suvi M.; Clish, Clary B.; Orešič, Matej; Huttenhower, Curtis; Knip, Mikael

    2015-01-01

    SUMMARY 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 infants genetically predisposed to T1D. Modeling trajectories of microbial abundances through infancy revealed a subset of microbial relationships shared across most subjects. Although strain composition of a given species was highly variable between individuals, it was stable within individuals throughout infancy. Metabolic composition and metabolic pathway abundance remained constant across time. A marked drop in alpha-diversity was observed in T1D progressors in the time-window between seroconversion and T1D diagnosis, accompanied by spikes in inflammation-favoring organisms, gene functions, and serum and stool metabolites. This work identifies trends in the development of the human infant gut microbiome along with specific alterations that precede T1D onset and distinguish T1D progressors from non-progressors. PMID:25662751

  20. Folic acid handling by the human gut: implications for food fortification and supplementation123

    PubMed Central

    Patanwala, Imran; King, Maria J; Barrett, David A; Rose, John; Jackson, Ralph; Hudson, Mark; Philo, Mark; Dainty, Jack R; Wright, Anthony JA; Finglas, Paul M; Jones, David E

    2014-01-01

    Background: Current thinking, which is based mainly on rodent studies, is that physiologic doses of folic acid (pterylmonoglutamic acid), such as dietary vitamin folates, are biotransformed in the intestinal mucosa and transferred to the portal vein as the natural circulating plasma folate, 5-methyltetrahydrofolic acid (5-MTHF) before entering the liver and the wider systemic blood supply. Objective: We tested the assumption that, in humans, folic acid is biotransformed (reduced and methylated) to 5-MTHF in the intestinal mucosa. Design: We conducted a crossover study in which we sampled portal and peripheral veins for labeled folate concentrations after oral ingestion with physiologic doses of stable-isotope–labeled folic acid or the reduced folate 5-formyltetrahydrofolic acid (5-FormylTHF) in 6 subjects with a transjugular intrahepatic porto systemic shunt (TIPSS) in situ. The TIPSS allowed blood samples to be taken from the portal vein. Results: Fifteen minutes after a dose of folic acid, 80 ± 12% of labeled folate in the hepatic portal vein was unmodified folic acid. In contrast, after a dose of labeled 5-FormylTHF, only 4 ± 18% of labeled folate in the portal vein was unmodified 5-FormylTHF, and the rest had been converted to 5-MTHF after 15 min (postdose). Conclusions: The human gut appears to have a very efficient capacity to convert reduced dietary folates to 5-MTHF but limited ability to reduce folic acid. Therefore, large amounts of unmodified folic acid in the portal vein are probably attributable to an extremely limited mucosal cell dihydrofolate reductase (DHFR) capacity that is necessary to produce tetrahydrofolic acid before sequential methylation to 5-MTHF. This process would suggest that humans are reliant on the liver for folic acid reduction even though it has a low and highly variable DHFR activity. Therefore, chronic liver exposure to folic acid in humans may induce saturation, which would possibly explain reports of systemic circulation of

  1. Correlation network analysis reveals relationships between diet-induced changes in human gut microbiota and metabolic health

    PubMed Central

    Kelder, T; Stroeve, J H M; Bijlsma, S; Radonjic, M; Roeselers, G

    2014-01-01

    Background: Recent evidence suggests that the gut microbiota plays an important role in human metabolism and energy homeostasis and is therefore a relevant factor in the assessment of metabolic health and flexibility. Understanding of these host–microbiome interactions aids the design of nutritional strategies that act via modulation of the microbiota. Nevertheless, relating gut microbiota composition to host health states remains challenging because of the sheer complexity of these ecosystems and the large degrees of interindividual variation in human microbiota composition. Methods: We assessed fecal microbiota composition and host response patterns of metabolic and inflammatory markers in 10 apparently healthy men subjected to a high-fat high-caloric diet (HFHC, 1300 kcal/day extra) for 4 weeks. DNA was isolated from stool and barcoded 16S rRNA gene amplicons were sequenced. Metabolic health parameters, including anthropomorphic and blood parameters, where determined at t=0 and t=4 weeks. Results: A correlation network approach revealed diet-induced changes in Bacteroides levels related to changes in carbohydrate oxidation rates, whereas the change in Firmicutes correlates with changes in fat oxidation. These results were confirmed by multivariate models. We identified correlations between microbial diversity indices and several inflammation-related host parameters that suggest a relation between diet-induced changes in gut microbiota diversity and inflammatory processes. Conclusions: This approach allowed us to identify significant correlations between abundances of microbial taxa and diet-induced shifts in several metabolic health parameters. Constructed correlation networks provide an overview of these relations, revealing groups of correlations that are of particular interest for explaining host health aspects through changes in the gut microbiota. PMID:24979151

  2. Prebiotic Potential of a Maize-Based Soluble Fibre and Impact of Dose on the Human Gut Microbiota

    PubMed Central

    Costabile, Adele; Deaville, Eddie R.; Morales, Agustin Martin; Gibson, Glenn R.

    2016-01-01

    Dietary management of the human gut microbiota towards a more beneficial composition is one approach that may improve host health. To date, a large number of human intervention studies have demonstrated that dietary consumption of certain food products can result in significant changes in the composition of the gut microbiota i.e. the prebiotic concept. Thus the prebiotic effect is now established as a dietary approach to increase beneficial gut bacteria and it has been associated with modulation of health biomarkers and modulation of the immune system. Promitor™ Soluble Corn Fibre (SCF) is a well-known maize-derived source of dietary fibre with potential selective fermentation properties. Our aim was to determine the optimum prebiotic dose of tolerance, desired changes to microbiota and fermentation of SCF in healthy adult subjects. A double-blind, randomised, parallel study was completed where volunteers (n = 8/treatment group) consumed 8, 14 or 21 g from SCF (6, 12 and 18 g/fibre delivered respectively) over 14-d. Over the range of doses studied, SCF was well tolerated Numbers of bifidobacteria were significantly higher for the 6 g/fibre/day compared to 12g and 18g/fibre delivered/day (mean 9.25 and 9.73 Log10 cells/g fresh faeces in the pre-treatment and treatment periods respectively). Such a numerical change of 0.5 Log10 bifidobacteria/g fresh faeces is consistent with those changes observed for inulin-type fructans, which are recognised prebiotics. A possible prebiotic effect of SCF was therefore demonstrated by its stimulation of bifidobacteria numbers in the overall gut microbiota during a short-term intervention. PMID:26731113

  3. Diversity of the cultivable human gut microbiome involved in gluten metabolism: isolation of microorganisms with potential interest for coeliac disease.

    PubMed

    Caminero, Alberto; Herrán, Alexandra R; Nistal, Esther; Pérez-Andrés, Jenifer; Vaquero, Luis; Vivas, Santiago; Ruiz de Morales, José María G; Albillos, Silvia M; Casqueiro, Javier

    2014-05-01

    Gluten, a common component in the human diet, is capable of triggering coeliac disease pathogenesis in genetically predisposed individuals. Although the function of human digestive proteases in gluten proteins is quite well known, the role of intestinal microbiota in the metabolism of proteins is frequently underestimated. The aim of this study was the isolation and characterisation of the human gut bacteria involved in the metabolism of gluten proteins. Twenty-two human faecal samples were cultured with gluten as the principal nitrogen source, and 144 strains belonging to 35 bacterial species that may be involved in gluten metabolism in the human gut were isolated. Interestingly, 94 strains were able to metabolise gluten, 61 strains showed an extracellular proteolytic activity against gluten proteins, and several strains showed a peptidasic activity towards the 33-mer peptide, an immunogenic peptide in patients with coeliac disease. Most of the strains were classified within the phyla Firmicutes and Actinobacteria, mainly from the genera Lactobacillus, Streptococcus, Staphylococcus, Clostridium and Bifidobacterium. In conclusion, the human intestine exhibits a large variety of bacteria capable of utilising gluten proteins and peptides as nutrients. These bacteria could have an important role in gluten metabolism and could offer promising new treatment modalities for coeliac disease.

  4. The Complex Exogenous RNA Spectra in Human Plasma: An Interface with Human Gut Biota?

    PubMed Central

    Wang, Kai; Li, Hong; Yuan, Yue; Etheridge, Alton; Zhou, Yong; Huang, David; Wilmes, Paul; Galas, David

    2012-01-01

    Human plasma has long been a rich source for biomarker discovery. It has recently become clear that plasma RNA molecules, such as microRNA, in addition to proteins are common and can serve as biomarkers. Surveying human plasma for microRNA biomarkers using next generation sequencing technology, we observed that a significant fraction of the circulating RNA appear to originate from exogenous species. With careful analysis of sequence error statistics and other controls, we demonstrated that there is a wide range of RNA from many different organisms, including bacteria and fungi as well as from other species. These RNAs may be associated with protein, lipid or other molecules protecting them from RNase activity in plasma. Some of these RNAs are detected in intracellular complexes and may be able to influence cellular activities under in vitro conditions. These findings raise the possibility that plasma RNAs of exogenous origin may serve as signaling molecules mediating for example the human-microbiome interaction and may affect and/or indicate the state of human health. PMID:23251414

  5. Gordonibacter urolithinfaciens sp. nov., a urolithin-producing bacterium isolated from the human gut.

    PubMed

    Selma, María V; Tomás-Barberán, Francisco A; Beltrán, David; García-Villalba, Rocio; Espín, Juan C

    2014-07-01

    Urolithins are dibenzopyranone metabolites that exert anti-inflammatory activity in vivo and are produced by the gut microbiota from the dietary polyphenols ellagic acid (EA) and ellagitannins. However, the bacteria involved in this process remain unknown. We report here a novel bacterium, strain CEBAS 1/15P(T), capable of metabolizing EA to urolithins, that was isolated from healthy human faeces and characterized by determining phenotypic, biochemical and molecular methods. The strain was related to Gordonibacter pamelaeae 7-10-1-b(T), the type and only reported strain of the only species of the genus Gordonibacter, with about 97% 16S rRNA gene sequence similarity; they were both obligately anaerobic, non-spore-forming, Gram-stain-positive, short-rods/coccobacilli and metabolized only small numbers of carbon sources. L-Fucose, D-fructose, turanose, D-galacturonic acid and α-ketobutyric acid were metabolized by strain CEBAS 1/15P(T), while G. pamelaeae was negative for metabolism of these compounds. The whole-cell fatty acids consisted predominantly of saturated fatty acids (70%); strain CEBAS 1/15P(T) differed significantly from G. pamelaeae in the major fatty acid, which was C18 : 1ω9c, while anteiso-C15 : 0 was the major component for G. pamelaeae. The presence of a number of different fatty acid peaks, especially C19 : 0 cyclo and C18 : 1ω6c, was also indicative of distinct species. Six glycolipids (GL1-6) were recognized, while, in G. pamelaeae, only four glycolipids were described. On the basis of these data, the novel species Gordonibacter urolithinfaciens sp. nov. is described, with strain CEBAS 1/15P(T) ( = DSM 27213(T) = CCUG 64261(T)) as the type strain.

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

    PubMed

    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.

  7. A possible link of gut microbiota alteration in type 2 diabetes and Alzheimer's disease pathogenicity: an update.

    PubMed

    Alam, Mohammad Z; Alam, Qamre; Kamal, Mohammad A; Abuzenadah, Adel M; Haque, Absarul

    2014-04-01

    Imbalances in gut microbiota are associated with metabolic disorder, which are a group of obesity-related metabolic abnormalities that increase an individual's risk of developing type 2 diabetes (T2D) and Alzheimer's disease (AD). Although a number of risk factors have been postulated that may trigger the development of AD, the root cause of this disease is still a matter of debate. This review further investigates the etiology of AD by accumulating the current role played by gut microbiota in human, and trying to establish an inter-link between T2D and AD pathogenesis. There is a growing body of evidence which suggests that obesity is associated with alteration in the normal gut flora, reduced bacterial diversity, metabolic pathways and altered representation of bacterial genes. Obesity and T2D are considered to be induced as a result of changes within the composition of gut microbiota. The evidence gathered so far clearly advocates the involvement of gut microbes in causing obesity, a state of chronic and low-grade inflammation. Hence, understanding the microbiota of the gut is significant in relation to inflammation, as it is a key contributor for diabetes which has a direct relation to the AD pathogenesis. Comparative analysis of gut microbiota may enable further novel insight into the complex biology of AD, which is very important in order to take preventive measure such as early diagnosis, identification of new therapeutic targets and development of novel drugs.

  8. Active and secreted IgA-coated bacterial fractions from the human gut reveal an under-represented microbiota core

    PubMed Central

    D'Auria, Giuseppe; Peris-Bondia, Francesc; Džunková, Mária; Mira, Alex; Collado, Maria Carmen; Latorre, Amparo; Moya, Andrés

    2013-01-01

    Host-associated microbiota varies in distribution depending on the body area inhabited. Gut microbes are known to interact with the human immune system, maintaining gut homoeostasis. Thus, we studied whether secreted-IgA (S-IgA) coat specific microbial taxa without inducing strong immune responses. To do so, we fractionated gut microbiota by flow cytometry. We found that active and S-IgA-coated bacterial fractions were characterized by a higher diversity than those observed in raw faecal suspensions. A long-tail effect was observed in family distribution, revealing that rare bacteria represent up to 20% of total diversity. While Firmicutes was the most abundant phylum, the majority of its sequences were not assigned at the genus level. Finally, the single-cell-based approach enabled us to focus on active and S-IgA-coated bacteria. Thus, we revealed a microbiota core common to the healthy volunteers participating in the study. Interestingly, this core was composed mainly of low frequency taxa (e.g. Sphingomonadaceae). PMID:24343271

  9. Going viral: next generation sequencing applied to human gut phage populations

    PubMed Central

    Reyes, Alejandro; Semenkovich, Nicholas P.; Whiteson, Katrine; Rohwer, Forest; Gordon, Jeffrey I.

    2013-01-01

    Over the past decade researchers have begun to characterize viral diversity using metagenomic methods. These studies have shown that viruses, the majority of which infect bacteria (bacteriophages), are likely the most genetically diverse components of the biosphere. Here we briefly review the incipient rise of a phage biology renaissance catalyzed by recent advances in next generation sequencing. We explore how work characterizing phage diversity and their lifestyles in the gut is changing our view of ourselves as supra-organisms. Finally, we discuss how a new appreciation of phage dynamics may yield new applications for phage therapies designed to manipulate the structure and functions of our gut microbiomes. PMID:22864264

  10. Dysbiosis gut microbiota associated with inflammation and impaired mucosal immune function in intestine of humans with non-alcoholic fatty liver disease

    PubMed Central

    Jiang, Weiwei; Wu, Na; Wang, Xuemei; Chi, Yujing; Zhang, Yuanyuan; Qiu, Xinyun; Hu, Ying; Li, Jing; Liu, Yulan

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) has recently been considered to be under the influence of the gut microbiota, which might exert toxic effects on the human host after intestinal absorption and delivery to the liver via the portal vein. In this study, the composition of the gut microbiota in NAFLD patients and healthy subjects was determined via 16S ribosomal RNA Illumina next-generation sequencing. Among those taxa displaying greater than 0.1% average abundance in all samples, five genera, including Alistipes and Prevotella, were significantly more abundant in the gut microbiota of healthy subjects compared to NAFLD patients. Alternatively, Escherichia, Anaerobacter, Lactobacillus and Streptococcus were increased in the gut microbiota of NAFLD patients compared to healthy subjects. In addition, decreased numbers of CD4+ and CD8+ T lymphocytes and increased levels of TNF-α, IL-6 and IFN-γ were detected in the NAFLD group compared to the healthy group. Furthermore, irregularly arranged microvilli and widened tight junctions were observed in the gut mucosa of the NAFLD patients via transmission electron microscopy. We postulate that aside from dysbiosis of the gut microbiota, gut microbiota-mediated inflammation of the intestinal mucosa and the related impairment in mucosal immune function play an important role in the pathogenesis of NAFLD. PMID:25644696

  11. Related actions of probiotics and antibiotics on gut microbiota and weight modification.

    PubMed

    Angelakis, Emmanouil; Merhej, Vicky; Raoult, Didier

    2013-10-01

    Antibiotics and probiotics are widely used as growth promoters in agriculture. Most antibiotics prescribed in clinical practice are natural products that originate from Streptomyces spp, which were first used as agricultural probiotics. Antibiotics and probiotics both modify the gut microbiota. The effect of a probiotic species on the digestive flora depends on the strain and is largely determined by bacteriocin production. In human beings, as in animals, specific probiotics are associated with weight gain or loss. Improved understanding of the ability of specific probiotics to harvest energy from the host diet might lead to development of new treatments for obesity and malnutrition. In this Review, we present the effects of probiotics and antibiotics on the gut microbiota of human beings and animals and discuss their potential therapeutic use as interventions for weight gain and loss in human beings.

  12. Methods for Improving Human Gut Microbiome Data by Reducing Variability through Sample Processing and Storage of Stool.

    PubMed

    Gorzelak, Monika A; Gill, Sandeep K; Tasnim, Nishat; Ahmadi-Vand, Zahra; Jay, Michael; Gibson, Deanna L

    2015-01-01

    Gut microbiome community analysis is used to understand many diseases like inflammatory bowel disease, obesity, and diabetes. Sampling methods are an important consideration for human microbiome research, yet are not emphasized in many studies. In this study, we demonstrate that the preparation, handling, and storage of human faeces are critical processes that alter the outcomes of downstream DNA-based bacterial community analyses via qPCR. We found that stool subsampling resulted in large variability of gut microbiome data due to different microenvironments harbouring various taxa within an individual stool. However, we reduced intra-sample variability by homogenizing the entire stool sample in liquid nitrogen and subsampling from the resulting crushed powder prior to DNA extraction. We experimentally determined that the bacterial taxa varied with room temperature storage beyond 15 minutes and beyond three days storage in a domestic frost-free freezer. While freeze thawing only had an effect on bacterial taxa abundance beyond four cycles, the use of samples stored in RNAlater should be avoided as overall DNA yields were reduced as well as the detection of bacterial taxa. Overall we provide solutions for processing and storing human stool samples that reduce variability of microbiome data. We recommend that stool is frozen within 15 minutes of being defecated, stored in a domestic frost-free freezer for less than three days, and homogenized prior to DNA extraction. Adoption of these simple protocols will have a significant and positive impact on future human microbiome research. PMID:26252519

  13. Methods for Improving Human Gut Microbiome Data by Reducing Variability through Sample Processing and Storage of Stool.

    PubMed

    Gorzelak, Monika A; Gill, Sandeep K; Tasnim, Nishat; Ahmadi-Vand, Zahra; Jay, Michael; Gibson, Deanna L

    2015-01-01

    Gut microbiome community analysis is used to understand many diseases like inflammatory bowel disease, obesity, and diabetes. Sampling methods are an important consideration for human microbiome research, yet are not emphasized in many studies. In this study, we demonstrate that the preparation, handling, and storage of human faeces are critical processes that alter the outcomes of downstream DNA-based bacterial community analyses via qPCR. We found that stool subsampling resulted in large variability of gut microbiome data due to different microenvironments harbouring various taxa within an individual stool. However, we reduced intra-sample variability by homogenizing the entire stool sample in liquid nitrogen and subsampling from the resulting crushed powder prior to DNA extraction. We experimentally determined that the bacterial taxa varied with room temperature storage beyond 15 minutes and beyond three days storage in a domestic frost-free freezer. While freeze thawing only had an effect on bacterial taxa abundance beyond four cycles, the use of samples stored in RNAlater should be avoided as overall DNA yields were reduced as well as the detection of bacterial taxa. Overall we provide solutions for processing and storing human stool samples that reduce variability of microbiome data. We recommend that stool is frozen within 15 minutes of being defecated, stored in a domestic frost-free freezer for less than three days, and homogenized prior to DNA extraction. Adoption of these simple protocols will have a significant and positive impact on future human microbiome research.

  14. Species-function relationships shape ecological properties of the human gut microbiome.

    PubMed

    Vieira-Silva, Sara; Falony, Gwen; Darzi, Youssef; Lima-Mendez, Gipsi; Garcia Yunta, Roberto; Okuda, Shujiro; Vandeputte, Doris; Valles-Colomer, Mireia; Hildebrand, Falk; Chaffron, Samuel; Raes, Jeroen

    2016-01-01

    Despite recent progress, the organization and ecological properties of the intestinal microbial ecosystem remain under-investigated. Here, using a manually curated metabolic module framework for (meta-)genomic data analysis, we studied species-function relationships in gut microbial genomes and microbiomes. Half of gut-associated species were found to be generalists regarding overall substrate preference, but we observed significant genus-level metabolic diversification linked to bacterial life strategies. Within each genus, metabolic consistency varied significantly, being low in Firmicutes genera and higher in Bacteroides. Differentiation of fermentable substrate degradation potential contributed to metagenomic functional repertoire variation between individuals, with different enterotypes showing distinct saccharolytic/proteolytic/lipolytic profiles. Finally, we found that module-derived functional redundancy was reduced in the low-richness Bacteroides enterotype, potentially indicating a decreased resilience to perturbation, in line with its frequent association to dysbiosis. These results provide insights into the complex structure of gut microbiome-encoded metabolic properties and emphasize the importance of functional and ecological assessment of gut microbiome variation in clinical studies.

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

    PubMed Central

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

    2014-01-01

    Traditionally bacteria have been considered as either pathogens, commensals or symbionts. The mammal gut harbors 1014 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. PMID:25548471

  16. Arsenic Metabolism by Human Gut Microbiota upon In Vitro Digestion of Contaminated Soils

    EPA Science Inventory

    Background: Speciation analysis is essential when evaluating risks from arsenic (As) exposure. In an oral exposure scenario, the importance of presystemic metabolism by gut microorganisms has been evidenced with in vivo animal models and in vitro experiments with ...

  17. Species-function relationships shape ecological properties of the human gut microbiome.

    PubMed

    Vieira-Silva, Sara; Falony, Gwen; Darzi, Youssef; Lima-Mendez, Gipsi; Garcia Yunta, Roberto; Okuda, Shujiro; Vandeputte, Doris; Valles-Colomer, Mireia; Hildebrand, Falk; Chaffron, Samuel; Raes, Jeroen

    2016-01-01

    Despite recent progress, the organization and ecological properties of the intestinal microbial ecosystem remain under-investigated. Here, using a manually curated metabolic module framework for (meta-)genomic data analysis, we studied species-function relationships in gut microbial genomes and microbiomes. Half of gut-associated species were found to be generalists regarding overall substrate preference, but we observed significant genus-level metabolic diversification linked to bacterial life strategies. Within each genus, metabolic consistency varied significantly, being low in Firmicutes genera and higher in Bacteroides. Differentiation of fermentable substrate degradation potential contributed to metagenomic functional repertoire variation between individuals, with different enterotypes showing distinct saccharolytic/proteolytic/lipolytic profiles. Finally, we found that module-derived functional redundancy was reduced in the low-richness Bacteroides enterotype, potentially indicating a decreased resilience to perturbation, in line with its frequent association to dysbiosis. These results provide insights into the complex structure of gut microbiome-encoded metabolic properties and emphasize the importance of functional and ecological assessment of gut microbiome variation in clinical studies. PMID:27573110

  18. MetaQuery: a web server for rapid annotation and quantitative analysis of specific genes in the human gut microbiome

    PubMed Central

    Nayfach, Stephen; Fischbach, Michael A.; Pollard, Katherine S.

    2015-01-01

    Summary: Microbiome researchers frequently want to know how abundant a particular microbial gene or pathway is across different human hosts, including its association with disease and its co-occurrence with other genes or microbial taxa. With thousands of publicly available metagenomes, these questions should be easy to answer. However, computational barriers prevent most researchers from conducting such analyses. We address this problem with MetaQuery, a web application for rapid and quantitative analysis of specific genes in the human gut microbiome. The user inputs one or more query genes, and our software returns the estimated abundance of these genes across 1267 publicly available fecal metagenomes from American, European and Chinese individuals. In addition, our application performs downstream statistical analyses to identify features that are associated with gene variation, including other query genes (i.e. gene co-variation), taxa, clinical variables (e.g. inflammatory bowel disease and diabetes) and average genome size. The speed and accessibility of MetaQuery are a step toward democratizing metagenomics research, which should allow many researchers to query the abundance and variation of specific genes in the human gut microbiome. Availability and implementation: http://metaquery.docpollard.org. Contact: snayfach@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26104745

  19. Hot topics in gut microbiota

    PubMed Central

    Simrén, Magnus; Buttle, Lisa; Guarner, Francisco

    2013-01-01

    The study of gut microbiota is a rapidly moving field of research, and the impact of gut microbial communities on human health is widely perceived as one of the most exciting advancements in biomedicine in recent years. The gut microbiota plays a key role in digestion, metabolism and immune function, and has widespread impact beyond the gastrointestinal tract. Changes in the biodiversity of the gut microbiota are associated with far reaching consequences on host health and development. Further understanding of the importance of developing and maintaining gut microbiota diversity may lead to targeted interventions for health promotion, disease prevention and management. Diet, functional foods and gut microbiota transplantation are areas that have yielded some therapeutic success in modulating the gut microbiota, and warrant further investigation of their effects on various disease states. PMID:24917977

  20. Hot topics in gut microbiota.

    PubMed

    Doré, Joël; Simrén, Magnus; Buttle, Lisa; Guarner, Francisco

    2013-10-01

    The study of gut microbiota is a rapidly moving field of research, and the impact of gut microbial communities on human health is widely perceived as one of the most exciting advancements in biomedicine in recent years. The gut microbiota plays a key role in digestion, metabolism and immune function, and has widespread impact beyond the gastrointestinal tract. Changes in the biodiversity of the gut microbiota are associated with far reaching consequences on host health and development. Further understanding of the importance of developing and maintaining gut microbiota diversity may lead to targeted interventions for health promotion, disease prevention and management. Diet, functional foods and gut microbiota transplantation are areas that have yielded some therapeutic success in modulating the gut microbiota, and warrant further investigation of their effects on various disease states.

  1. Bacillus rubiinfantis sp. nov. strain mt2T, a new bacterial species isolated from human gut

    PubMed Central

    Tidjiani Alou, M.; Rathored, J.; Khelaifia, S.; Michelle, C.; Brah, S.; Diallo, B.A.; Raoult, D.; Lagier, J.-C.

    2015-01-01

    Bacillus rubiinfantis sp. nov. strain mt2T is the type strain of B. rubiinfantis sp. nov., isolated from the fecal flora of a child with kwashiorkor in Niger. It is Gram-positive facultative anaerobic rod belonging to the Bacillaceae family. We describe the features of this organism alongside the complete genome sequence and annotation. The 4 311 083 bp long genome (one chromosome but no plasmid) contains 4028 protein-coding gene and 121 RNA genes including nine rRNA genes. PMID:27076912

  2. Bacillus niameyensis sp. nov., a new bacterial species isolated from human gut

    PubMed Central

    Tidjani Alou, M.; Rathored, J.; Traore, S.I.; Khelaifia, S.; Michelle, C.; Brah, S.; Diallo, B.A.; Raoult, D.; Lagier, J.-C.

    2015-01-01

    Bacillus niameyensis sp. nov. strain SIT3T (= CSUR P1266 = DSM 29725) is the type strain of B. niameyensis sp. nov. This Gram-positive strain was isolated from the digestive flora of a child with kwashiorkor and is a facultative anaerobic rod and a member of the Bacillaceae family. This organism is hereby described alongside its complete genome sequence and annotation. The 4  286  116 bp long genome (one chromosome but no plasmid) contains 4130 protein-coding and 66 RNA genes including five rRNA genes. PMID:27076913

  3. Vegetable microbiomes: is there a connection among opportunistic infections, human health and our ‘gut feeling'?

    PubMed Central

    Berg, Gabriele; Erlacher, Armin; Smalla, Kornelia; Krause, Robert

    2014-01-01

    The highly diverse microbiomes of vegetables are reservoirs for opportunistic and emerging pathogens. In recent years, an increased consumption, larger scale production and more efficient distribution of vegetables together with an increased number of immunocompromised individuals resulted in an enhanced number of documented outbreaks of human infections associated with the consumption of vegetables. Here we discuss the occurrence of potential pathogens in vegetable microbiomes, the impact of farming and processing practices, and plant and human health issues. Based on these results, we discuss the question if vegetables can serve as a source of infection for immunocompromised individuals as well as possible solutions to avoid outbreaks. Moreover, the potentially positive aspects of the vegetables microbiome for the gut microbiota and human health are presented. PMID:25186140

  4. Is it who you are or what you do that is important in the human gut?

    PubMed

    Avershina, E; Rudi, K

    2013-09-01

    The current leading view is that functionality and not phylotype is the most important determinant for the services provided by the gut microbiota. Here we present an alternative opinion, advocating the importance of phylotype in addition to function. We believe the literature is misled by technical artifacts in defining operational taxonomic units (OTUs), which are binned groups of bacteria based on sequence homology. Furthermore, the current metagenomic approaches where the total DNA in a sample is mixed prior to sequencing and subsequently resolved by a bioinformatics approach, are highly error prone with respect to both functional and phylotype assignments. We argue that the directions of the OTU and metagenome errors are such that stable phylotypes are overlooked, while functional stability is overestimated. Taking these errors into account, we propose that phylotype represents an interface for functionality, and is for this reason an important determinant for the services provided by the gut microbiota to the host.

  5. Impact of demographics on human gut microbial diversity in a US Midwest population.

    PubMed

    Chen, Jun; Ryu, Euijung; Hathcock, Matthew; Ballman, Karla; Chia, Nicholas; Olson, Janet E; Nelson, Heidi

    2016-01-01

    The clinical utility of microbiome biomarkers depends on the reliable and reproducible nature of comparative results. Underappreciation of the variation associated with common demographic, health, and behavioral factors may confound associations of interest and generate false positives. Here, we present the Midwestern Reference Panel (MWRP), a resource for comparative gut microbiome studies conducted in the Midwestern United States. We analyzed the relationships between demographic and health behavior-related factors and the microbiota in this cohort, and estimated their effect sizes. Most variables investigated were associated with the gut microbiota. Specifically, body mass index (BMI), race, sex, and alcohol use were significantly associated with microbial β-diversity (P < 0.05, unweighted UniFrac). BMI, race and alcohol use were also significantly associated with microbial α-diversity (P < 0.05, species richness). Tobacco use showed a trend toward association with the microbiota (P < 0.1, unweighted UniFrac). The effect sizes of the associations, as quantified by adjusted R(2) values based on unweighted UniFrac distances, were small (< 1% for all variables), indicating that these factors explain only a small percentage of overall microbiota variability. Nevertheless, the significant associations between these variables and the gut microbiota suggest that they could still be potential confounders in comparative studies and that controlling for these variables in study design, which is the main objective of the MWRP, is important for increasing reproducibility in comparative microbiome studies. PMID:26839739

  6. Isolation and gut microbiota modulation of antibiotic-resistant probiotics from human feces.

    PubMed

    Tian, Peng; Xu, Bo; Sun, Hanxiao; Li, Xiuying; Li, Zhi; Wei, Pijin

    2014-08-01

    Antibiotic-resistant probiotics may be advantageous for antibiotic-induced gut microbiota imbalance. In this article, we aimed to isolate antibiotic-resistant bacteria as potential probiotics. Feces from 3 healthy adults and 2 infants were used to isolate the antibiotic-resistant bacteria. Then we established gut microbiota imbalance mice model by antibiotics treatment and used it to assess the effect of the probiotics. Finally, we identified 8 isolates, and 6 of them were used as probiotics cocktail. Number of anaerobe, lactobacilli, and Bifidobacterium in feces were higher in the probiotic group (9.47±0.35 log10CFU/g, 8.74±0.18 log10CFU/g, 7.24±0.38 log10CFU/g, respectively) compared with model group (P<0.05). Richness and diversity index of probiotic group (19.79±0.29 and 2.95±0.06, respectively) were larger than model group (P<0.05). Diarrhea and mucosal edema had been alleviated during probiotic treatment. Our results validated that bacteriotherapy was available to treat gut microbiota imbalance.

  7. Impact of demographics on human gut microbial diversity in a US Midwest population

    PubMed Central

    Chen, Jun; Ryu, Euijung; Hathcock, Matthew; Ballman, Karla; Chia, Nicholas; Olson, Janet E

    2016-01-01

    The clinical utility of microbiome biomarkers depends on the reliable and reproducible nature of comparative results. Underappreciation of the variation associated with common demographic, health, and behavioral factors may confound associations of interest and generate false positives. Here, we present the Midwestern Reference Panel (MWRP), a resource for comparative gut microbiome studies conducted in the Midwestern United States. We analyzed the relationships between demographic and health behavior-related factors and the microbiota in this cohort, and estimated their effect sizes. Most variables investigated were associated with the gut microbiota. Specifically, body mass index (BMI), race, sex, and alcohol use were significantly associated with microbial β-diversity (P < 0.05, unweighted UniFrac). BMI, race and alcohol use were also significantly associated with microbial α-diversity (P < 0.05, species richness). Tobacco use showed a trend toward association with the microbiota (P < 0.1, unweighted UniFrac). The effect sizes of the associations, as quantified by adjusted R2 values based on unweighted UniFrac distances, were small (< 1% for all variables), indicating that these factors explain only a small percentage of overall microbiota variability. Nevertheless, the significant associations between these variables and the gut microbiota suggest that they could still be potential confounders in comparative studies and that controlling for these variables in study design, which is the main objective of the MWRP, is important for increasing reproducibility in comparative microbiome studies. PMID:26839739

  8. Suppression of inflammation by helminths: a role for the gut microbiota?

    PubMed Central

    Giacomin, Paul; Croese, John; Krause, Lutz; Loukas, Alex; Cantacessi, Cinzia

    2015-01-01

    Multiple recent investigations have highlighted the promise of helminth-based therapies for the treatment of inflammatory disorders of the intestinal tract of humans, including inflammatory bowel disease and coeliac disease. However, the mechanisms by which helminths regulate immune responses, leading to the amelioration of symptoms of chronic inflammation are unknown. Given the pivotal roles of the intestinal microbiota in the pathogenesis of these disorders, it has been hypothesized that helminth-induced modifications of the gut commensal flora may be responsible for the therapeutic properties of gastrointestinal parasites. In this article, we review recent progress in the elucidation of host–parasite–microbiota interactions in both animal models of chronic inflammation and humans, and provide a working hypothesis of the role of the gut microbiota in helminth-induced suppression of inflammation. PMID:26150662

  9. Suppression of inflammation by helminths: a role for the gut microbiota?

    PubMed

    Giacomin, Paul; Croese, John; Krause, Lutz; Loukas, Alex; Cantacessi, Cinzia

    2015-08-19

    Multiple recent investigations have highlighted the promise of helminth-based therapies for the treatment of inflammatory disorders of the intestinal tract of humans, including inflammatory bowel disease and coeliac disease. However, the mechanisms by which helminths regulate immune responses, leading to the amelioration of symptoms of chronic inflammation are unknown. Given the pivotal roles of the intestinal microbiota in the pathogenesis of these disorders, it has been hypothesized that helminth-induced modifications of the gut commensal flora may be responsible for the therapeutic properties of gastrointestinal parasites. In this article, we review recent progress in the elucidation of host-parasite-microbiota interactions in both animal models of chronic inflammation and humans, and provide a working hypothesis of the role of the gut microbiota in helminth-induced suppression of inflammation.

  10. Prebiotic inulin: Useful dietary adjuncts to manipulate the livestock gut microflora.

    PubMed

    Samanta, A K; Jayapal, Natasha; Senani, S; Kolte, A P; Sridhar, Manpal

    2013-05-07

    In recent years, there has been a growing appreciation on the relevance of gastrointestinal microflora in both ruminants and non-ruminants owing to revelation of their role in several physiological functions including digestion, nutrient utilization, pathogen exclusion, gastrointestinal development, immunity system, gut gene expression and quality of animal products. The ban imposed on the use of antibiotics and hormones in feed has compelled animal researchers in finding an alternative which could overcome the issues of conventional feed additives. Though the concept of prebiotic was evolved keeping in mind the gastrointestinal flora of human beings, presently animal researchers are exploring the efficiency of prebiotic (inulin) for modulating the gut ecosystem of both ruminants and non-ruminants. It was revealed that prebiotic inulin is found to exhibit desirable changes in the gut of non-ruminants like poultry, swine, rabbit etc for augmenting gut health and improvement of product quality. Similarly, in ruminants the prebiotic reduces rumen ammonia nitrogen, methane production, increase microbial protein synthesis and live weight gains in calves. Unlike other feed additives, prebiotic exhibits its effect in multipronged ways for overall increase in the performances of the animals. In coming days, it is expected that prebiotics could be the part of diets in both ruminants and non-ruminants for enabling modulation of gut microflora vis a vis animals productivity in ecological ways.

  11. Prebiotic inulin: Useful dietary adjuncts to manipulate the livestock gut microflora

    PubMed Central

    Samanta, A.K.; Jayapal, Natasha; Senani, S.; Kolte, A.P.; Sridhar, Manpal

    2013-01-01

    In recent years, there has been a growing appreciation on the relevance of gastrointestinal microflora in both ruminants and non-ruminants owing to revelation of their role in several physiological functions including digestion, nutrient utilization, pathogen exclusion, gastrointestinal development, immunity system, gut gene expression and quality of animal products. The ban imposed on the use of antibiotics and hormones in feed has compelled animal researchers in finding an alternative which could overcome the issues of conventional feed additives. Though the concept of prebiotic was evolved keeping in mind the gastrointestinal flora of human beings, presently animal researchers are exploring the efficiency of prebiotic (inulin) for modulating the gut ecosystem of both ruminants and non-ruminants. It was revealed that prebiotic inulin is found to exhibit desirable changes in the gut of non-ruminants like poultry, swine, rabbit etc for augmenting gut health and improvement of product quality. Similarly, in ruminants the prebiotic reduces rumen ammonia nitrogen, methane production, increase microbial protein synthesis and live weight gains in calves. Unlike other feed additives, prebiotic exhibits its effect in multipronged ways for overall increase in the performances of the animals. In coming days, it is expected that prebiotics could be the part of diets in both ruminants and non-ruminants for enabling modulation of gut microflora vis a vis animals productivity in ecological ways. PMID:24159277

  12. big bang gene modulates gut immune tolerance in Drosophila

    PubMed Central

    Bonnay, François; Cohen-Berros, Eva; Hoffmann, Martine; Kim, Sabrina Y.; Boulianne, Gabrielle L.; Hoffmann, Jules A.; Matt, Nicolas; Reichhart, Jean-Marc

    2013-01-01

    Chronic inflammation of the intestine is detrimental to mammals. Similarly, constant activation of the immune response in the gut by the endogenous flora is suspected to be harmful to Drosophila. Therefore, the innate immune response in the gut of Drosophila melanogaster is tightly balanced to simultaneously prevent infections by pathogenic microorganisms and tolerate the endogenous flora. Here we describe the role of the big bang (bbg) gene, encoding multiple membrane-associated PDZ (PSD-95, Discs-large, ZO-1) domain-containing protein isoforms, in the modulation of the gut immune response. We show that in the adult Drosophila midgut, BBG is present at the level of the septate junctions, on the apical side of the enterocytes. In the absence of BBG, these junctions become loose, enabling the intestinal flora to trigger a constitutive activation of the anterior midgut immune response. This chronic epithelial inflammation leads to a reduced lifespan of bbg mutant flies. Clearing the commensal flora by antibiotics prevents the abnormal activation of the gut immune response and restores a normal lifespan. We now provide genetic evidence that Drosophila septate junctions are part of the gut immune barrier, a function that is evolutionarily conserved in mammals. Collectively, our data suggest that septate junctions are required to maintain the subtle balance between immune tolerance and immune response in the Drosophila gut, which represents a powerful model to study inflammatory bowel diseases. PMID:23378635

  13. big bang gene modulates gut immune tolerance in Drosophila.

    PubMed

    Bonnay, François; Cohen-Berros, Eva; Hoffmann, Martine; Kim, Sabrina Y; Boulianne, Gabrielle L; Hoffmann, Jules A; Matt, Nicolas; Reichhart, Jean-Marc

    2013-02-19

    Chronic inflammation of the intestine is detrimental to mammals. Similarly, constant activation of the immune response in the gut by the endogenous flora is suspected to be harmful to Drosophila. Therefore, the innate immune response in the gut of Drosophila melanogaster is tightly balanced to simultaneously prevent infections by pathogenic microorganisms and tolerate the endogenous flora. Here we describe the role of the big bang (bbg) gene, encoding multiple membrane-associated PDZ (PSD-95, Discs-large, ZO-1) domain-containing protein isoforms, in the modulation of the gut immune response. We show that in the adult Drosophila midgut, BBG is present at the level of the septate junctions, on the apical side of the enterocytes. In the absence of BBG, these junctions become loose, enabling the intestinal flora to trigger a constitutive activation of the anterior midgut immune response. This chronic epithelial inflammation leads to a reduced lifespan of bbg mutant flies. Clearing the commensal flora by antibiotics prevents the abnormal activation of the gut immune response and restores a normal lifespan. We now provide genetic evidence that Drosophila septate junctions are part of the gut immune barrier, a function that is evolutionarily conserved in mammals. Collectively, our data suggest that septate junctions are required to maintain the subtle balance between immune tolerance and immune response in the Drosophila gut, which represents a powerful model to study inflammatory bowel diseases.

  14. big bang gene modulates gut immune tolerance in Drosophila.

    PubMed

    Bonnay, François; Cohen-Berros, Eva; Hoffmann, Martine; Kim, Sabrina Y; Boulianne, Gabrielle L; Hoffmann, Jules A; Matt, Nicolas; Reichhart, Jean-Marc

    2013-02-19

    Chronic inflammation of the intestine is detrimental to mammals. Similarly, constant activation of the immune response in the gut by the endogenous flora is suspected to be harmful to Drosophila. Therefore, the innate immune response in the gut of Drosophila melanogaster is tightly balanced to simultaneously prevent infections by pathogenic microorganisms and tolerate the endogenous flora. Here we describe the role of the big bang (bbg) gene, encoding multiple membrane-associated PDZ (PSD-95, Discs-large, ZO-1) domain-containing protein isoforms, in the modulation of the gut immune response. We show that in the adult Drosophila midgut, BBG is present at the level of the septate junctions, on the apical side of the enterocytes. In the absence of BBG, these junctions become loose, enabling the intestinal flora to trigger a constitutive activation of the anterior midgut immune response. This chronic epithelial inflammation leads to a reduced lifespan of bbg mutant flies. Clearing the commensal flora by antibiotics prevents the abnormal activation of the gut immune response and restores a normal lifespan. We now provide genetic evidence that Drosophila septate junctions are part of the gut immune barrier, a function that is evolutionarily conserved in mammals. Collectively, our data suggest that septate junctions are required to maintain the subtle balance between immune tolerance and immune response in the Drosophila gut, which represents a powerful model to study inflammatory bowel diseases. PMID:23378635

  15. Assessment of bacterial antibiotic resistance transfer in the gut.

    PubMed

    Schjørring, Susanne; Krogfelt, Karen A

    2011-01-01

    We assessed horizontal gene transfer between bacteria in the gastrointestinal (GI) tract. During the last decades, the emergence of antibiotic resistant strains and treatment failures of bacterial infections have increased the public awareness of antibiotic usage. The use of broad spectrum antibiotics creates a selective pressure on the bacterial flora, thus increasing the emergence of multiresistant bacteria, which results in a vicious circle of treatments and emergence of new antibiotic resistant bacteria. The human gastrointestinal tract is a massive reservoir of bacteria with a potential for both receiving and transferring antibiotic resistance genes. The increased use of fermented food products and probiotics, as food supplements and health promoting products containing massive amounts of bacteria acting as either donors and/or recipients of antibiotic resistance genes in the human GI tract, also contributes to the emergence of antibiotic resistant strains. This paper deals with the assessment of antibiotic resistance gene transfer occurring in the gut. PMID:21318188

  16. The host and the flora.

    PubMed

    Nuding, S; Antoni, L; Stange, E F

    2013-01-01

    To prevent bacterial overgrowth, colonization of the epithelium and subsequent translocation, the gastrointestinal tract maintains an effective mucosal barrier. Besides mucus the most important components of this protective system are epithelial antimicrobial peptides such as defensins, the cathelicidin LL-37, lysozyme, phospholipase A, and proteins with additional antimicrobial properties such as ubiquicidin, ribosomal proteins or histones. Commensal species may tolerate intestinal antimicrobial peptides, for example Bacteroides ssp. or Parabacteroides ssp. as major species in the human colon were highly resistant to the constitutive defensin HBD-1 and only susceptible to the inducible defensin HBD-3. Reduction of disulfide bonds is an important mechanism activating HBD-1. As several studies show, alterations in the expression of antimicrobial peptides directly influence the composition of the intestinal flora. Correspondingly, an increased production of defensins or inhibition of the processing of mouse defensins to their active form led to a quantitative shift of luminal and mucosal bacterial species. On the other hand, microorganisms also modulate the synthesis of host defensins by induction or inhibition of specific peptides. Lactobacilli, the probiotic strain Escherichia coli Nissle and Salmonella enteritica stimulate HBD-2 expression, whereas Shigella flexneri downregulates the synthesis of HBD-1, HBD-3 and LL-37. Thus, the proper balance between the luminal flora and the mucosa is a permanently dynamic, sensitive and host-specific relationship. PMID:24246976

  17. Complete Genome Sequence of Clostridium septicum Strain CSUR P1044, Isolated from the Human Gut Microbiota.

    PubMed

    Benamar, Samia; Cassir, Nadim; Caputo, Aurélia; Cadoret, Frédéric; La Scola, Bernard

    2016-01-01

    Clostridium septicum is one of the first pathogenic anaerobes to be identified. Here, we announce the genome draft sequence of C. septicum strain CSUR P1044 isolated from the gut of a healthy adult. Its chromosome genome consists of 3.2 Mbp with a plasmid of 32 Kbp. C. septicum strain CSUR P1044 has a G+C content of 27.5%, and is composed of 3,125 protein-coding genes together with 103 RNA genes, including 22 rRNA genes. PMID:27609912

  18. Complete Genome Sequence of Clostridium septicum Strain CSUR P1044, Isolated from the Human Gut Microbiota.

    PubMed

    Benamar, Samia; Cassir, Nadim; Caputo, Aurélia; Cadoret, Frédéric; La Scola, Bernard

    2016-01-01

    Clostridium septicum is one of the first pathogenic anaerobes to be identified. Here, we announce the genome draft sequence of C. septicum strain CSUR P1044 isolated from the gut of a healthy adult. Its chromosome genome consists of 3.2 Mbp with a plasmid of 32 Kbp. C. septicum strain CSUR P1044 has a G+C content of 27.5%, and is composed of 3,125 protein-coding genes together with 103 RNA genes, including 22 rRNA genes.

  19. Massilibacterium senegalense gen. nov., sp. nov., a new bacterial genus isolated from the human gut

    PubMed Central

    Tidjani Alou, M.; Rathored, J.; Lagier, J.-C.; Khelaifia, S.; Labas, N.; Sokhna, C.; Diallo, A.; Raoult, D.; Dubourg, G.

    2016-01-01

    Massilibacterium senegalense gen. nov., sp. nov., strain mt8T, is the type strain of Massilibacterium gen. nov., a new genus within the Bacillaceae family. This Gram-negative facultative anaerobic rod was isolated from the gut microbiota of a severely malnourished boy. Its phenotypic description is hereby presented with a complete annotation of its genome sequence. This genome is 5 697 950 bp long and contains 5615 protein-coding genes and 178 RNA genes, among which are 40 rRNA genes. PMID:26933503

  20. Complete Genome Sequence of Clostridium septicum Strain CSUR P1044, Isolated from the Human Gut Microbiota

    PubMed Central

    Benamar, Samia; Cassir, Nadim; Caputo, Aurélia; Cadoret, Frédéric

    2016-01-01

    Clostridium septicum is one of the first pathogenic anaerobes to be identified. Here, we announce the genome draft sequence of C. septicum strain CSUR P1044 isolated from the gut of a healthy adult. Its chromosome genome consists of 3.2 Mbp with a plasmid of 32 Kbp. C. septicum strain CSUR P1044 has a G+C content of 27.5%, and is composed of 3,125 protein-coding genes together with 103 RNA genes, including 22 rRNA genes. PMID:27609912

  1. The networks of human gut microbe-metabolite associations are different between health and irritable bowel syndrome.

    PubMed

    Shankar, Vijay; Homer, Daniel; Rigsbee, Laura; Khamis, Harry J; Michail, Sonia; Raymer, Michael; Reo, Nicholas V; Paliy, Oleg

    2015-08-01

    The goal of this study was to determine if fecal metabolite and microbiota profiles can serve as biomarkers of human intestinal diseases, and to uncover possible gut microbe-metabolite associations. We employed proton nuclear magnetic resonance to measure fecal metabolites of healthy children and those diagnosed with diarrhea-predominant irritable bowel syndrome (IBS-D). Metabolite levels were associated with fecal microbial abundances. Using several ordination techniques, healthy and irritable bowel syndrome (IBS) samples could be distinguished based on the metabolite profiles of fecal samples, and such partitioning was congruent with the microbiota-based sample separation. Measurements of individual metabolites indicated that the intestinal environment in IBS-D was characterized by increased proteolysis, incomplete anaerobic fermentation and possible change in methane production. By correlating metabolite levels with abundances of microbial genera, a number of statistically significant metabolite-genus associations were detected in stools of healthy children. No such associations were evident for IBS children. This finding complemented the previously observed reduction in the number of microbe-microbe associations in the distal gut of the same cohort of IBS-D children.

  2. The human gut microbiota: a dynamic interplay with the host from birth to senescence settled during childhood.

    PubMed

    Putignani, Lorenza; Del Chierico, Federica; Petrucca, Andrea; Vernocchi, Pamela; Dallapiccola, Bruno

    2014-07-01

    The microbiota "organ" is the central bioreactor of the gastrointestinal tract, populated by a total of 10(14) bacteria and characterized by a genomic content (microbiome), which represents more than 100 times the human genome. The microbiota plays an important role in child health by acting as a barrier against pathogens and their invasion with a highly dynamic modality, exerting metabolic multistep functions and stimulating the development of the host immune system, through well-organized programming, which influences all of the growth and aging processes. The advent of "omics" technologies (genomics, proteomics, metabolomics), characterized by complex technological platforms and advanced analytical and computational procedures, has opened new avenues to the knowledge of the gut microbiota ecosystem, clarifying some aspects on the establishment of microbial communities that constitute it, their modulation and active interaction with external stimuli as well as food, within the host genetic variability. With a huge interdisciplinary effort and an interface work between basic, translational, and clinical research, microbiologists, specialists in "-omics" disciplines, and clinicians are now clarifying the role of the microbiota in the programming process of several gut-related diseases, from the physiological symbiosis to the microbial dysbiosis stage, through an integrated systems biology approach.

  3. High protective efficacy of rice bran against human rotavirus diarrhea via enhancing probiotic growth, gut barrier function, and innate immunity.

    PubMed

    Yang, Xingdong; Twitchell, Erica; Li, Guohua; Wen, Ke; Weiss, Mariah; Kocher, Jacob; Lei, Shaohua; Ramesh, Ashwin; Ryan, Elizabeth P; Yuan, Lijuan

    2015-01-01

    Previously, we showed that rice bran (RB) was able to reduce human rotavirus (HRV) diarrhea in gnotobiotic pigs. Here, we investigated its effect on the growth of diarrhea-reducing probiotic Lactobacillus rhamnosus GG (LGG) and Escherichia coli Nissle (EcN), and the resulting effects on HRV diarrhea, gut epithelial health, permeability and innate immune responses during virulent HRV challenge. On 3, 5, and 7 days of age pigs were inoculated with 2 × 10(4) colony-forming-units LGG+EcN to initiate colonization. Daily RB supplementation (replacing 10% calorie intake) was started at 5 days of age and continued until euthanasia. A subset of pigs in each group was challenged orally with 10(5) focus-forming-units of virulent HRV at 33 days of age. RB completely prevented HRV diarrhea in LGG+EcN colonized pigs. RB significantly promoted the growth of both probiotic strains in the gut (~5 logs) and increased the body-weight-gain at 4-5 weeks of age compared to non-RB group. After HRV challenge, RB-fed pigs had significantly lower ileal mitotic index and villus width, and significantly increased intestinal IFN-γ and total IgA levels compared to non-RB group. Therefore, RB plus LGG+EcN colonization may represent a highly effective therapeutic approach against HRV and potentially a variety of other diarrhea-inducing enteric pathogens. PMID:26459937

  4. High protective efficacy of rice bran against human rotavirus diarrhea via enhancing probiotic growth, gut barrier function, and innate immunity

    PubMed Central

    Yang, Xingdong; Twitchell, Erica; Li, Guohua; Wen, Ke; Weiss, Mariah; Kocher, Jacob; Lei, Shaohua; Ramesh, Ashwin; Ryan, Elizabeth P.; Yuan, Lijuan

    2015-01-01

    Previously, we showed that rice bran (RB) was able to reduce human rotavirus (HRV) diarrhea in gnotobiotic pigs. Here, we investigated its effect on the growth of diarrhea-reducing probiotic Lactobacillus rhamnosus GG (LGG) and Escherichia coli Nissle (EcN), and the resulting effects on HRV diarrhea, gut epithelial health, permeability and innate immune responses during virulent HRV challenge. On 3, 5, and 7 days of age pigs were inoculated with 2 × 104 colony-forming-units LGG+EcN to initiate colonization. Daily RB supplementation (replacing 10% calorie intake) was started at 5 days of age and continued until euthanasia. A subset of pigs in each group was challenged orally with 105 focus-forming-units of virulent HRV at 33 days of age. RB completely prevented HRV diarrhea in LGG+EcN colonized pigs. RB significantly promoted the growth of both probiotic strains in the gut (~5 logs) and increased the body-weight-gain at 4–5 weeks of age compared to non-RB group. After HRV challenge, RB-fed pigs had significantly lower ileal mitotic index and villus width, and significantly increased intestinal IFN-γ and total IgA levels compared to non-RB group. Therefore, RB plus LGG+EcN colonization may represent a highly effective therapeutic approach against HRV and potentially a variety of other diarrhea-inducing enteric pathogens. PMID:26459937

  5. Gut epithelial barrier dysfunction in human immunodeficiency virus-hepatitis C virus coinfected patients: Influence on innate and acquired immunity

    PubMed Central

    Márquez, Mercedes; Fernández Gutiérrez del Álamo, Clotilde; Girón-González, José Antonio

    2016-01-01

    Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus (HIV)-infected patients have several non-acquired immunodeficiency syndrome (AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus (HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed. PMID:26819512

  6. Obesity and the gut microbiota.

    PubMed

    Flint, Harry J

    2011-11-01

    Gut microorganisms have the potential to influence weight gain and fat deposition through a variety of mechanisms. One factor is the ability of microorganisms in the large intestine to release energy by fermenting otherwise indigestible components of the diet ("energy harvest"). This energy becomes available to the host indirectly through the absorption of microbially produced short-chain fatty acids. Energy recovery from fiber will be largely determined by dietary intake and gut transit, but can also depend on the makeup of the gut microbiota. The species composition of the gut microbiota changes with diet composition, as has been shown in studies with obese individuals after reduced carbohydrate weight loss diets, or diets containing different nondigestible carbohydrates. There is conflicting evidence, however, on the extent to which gut microbiota composition differs between obese and nonobese humans. In contrast, there is increasing evidence to suggest that gut microorganisms and their metabolic products can influence gut hormones, inflammation, and gut motility. Any changes in gut microbiota composition that influence energy expenditure, satiety, and food intake have the potential to alter weight gain and weight loss, but a better understanding of the impact of different members of the gut microbial community upon host physiology is needed to establish these relationships. PMID:21992951

  7. Xylan utilization in human gut commensal bacteria is orchestrated by unique modular organization of polysaccharide-degrading enzymes

    PubMed Central

    Zhang, Meiling; Chekan, Jonathan R.; Dodd, Dylan; Hong, Pei-Ying; Radlinski, Lauren; Revindran, Vanessa; Nair, Satish K.; Mackie, Roderick I.; Cann, Isaac

    2014-01-01

    Enzymes that degrade dietary and host-derived glycans represent the most abundant functional activities encoded by genes unique to the human gut microbiome. However, the biochemical activities of a vast majority of the glycan-degrading enzymes are poorly understood. Here, we use transcriptome sequencing to understand the diversity of genes expressed by the human gut bacteria Bacteroides intestinalis and Bacteroides ovatus grown in monoculture with the abundant dietary polysaccharide xylan. The most highly induced carbohydrate active genes encode a unique glycoside hydrolase (GH) family 10 endoxylanase (BiXyn10A or BACINT_04215 and BACOVA_04390) that is highly conserved in the Bacteroidetes xylan utilization system. The BiXyn10A modular architecture consists of a GH10 catalytic module disrupted by a 250 amino acid sequence of unknown function. Biochemical analysis of BiXyn10A demonstrated that such insertion sequences encode a new family of carbohydrate-binding modules (CBMs) that binds to xylose-configured oligosaccharide/polysaccharide ligands, the substrate of the BiXyn10A enzymatic activity. The crystal structures of CBM1 from BiXyn10A (1.8 Å), a cocomplex of BiXyn10A CBM1 with xylohexaose (1.14 Å), and the CBM from its homolog in the Prevotella bryantii B14 Xyn10C (1.68 Å) reveal an unanticipated mode for ligand binding. A minimal enzyme mix, composed of the gene products of four of the most highly up-regulated genes during growth on wheat arabinoxylan, depolymerizes the polysaccharide into its component sugars. The combined biochemical and biophysical studies presented here provide a framework for understanding fiber metabolism by an important group within the commensal bacterial population known to influence human health. PMID:25136124

  8. Superantigen properties of a human sialoprotein involved in gut-associated immunity.

    PubMed Central

    Silverman, G J; Roben, P; Bouvet, J P; Sasano, M

    1995-01-01

    Protein Fv (pFv) is a recently described 175-kD gut-associated sialoprotein with a potent capacity for augmentation of antibody-dependent immune functions. To investigate the molecular basis for Fab-mediated binding of pFv, we evaluated a panel of 52 monoclonal IgM and found that approximately 40% bound pFv. Whereas the majority (> or = 75%) of V H3 and V H6 IgM strongly bound pFv, only a small minority (< 20%) of IgM from other V H families bound pFv, and these antibodies had weaker binding interactions. Inhibition studies suggested that all binding occurred at the same (or overlapping) site(s) on pFv. Surface plasmon resonance studies demonstrated binding affinity constants up to 6.7 x 10(8) M-1 for pFv. Biopanning of IgM and IgG Fab phage-display libraries with pFv preferentially selected for V H3 and V H6 antibodies, but also obtained certain V H4 IgM. V H sequence analyses of 36 pFv-binding antibodies revealed that binding did not correlate with CDR sequence, JH, or L chain usage. However, there was preferential selection of pFv binders with V H CDR3 of small size. These studies demonstrate that a protein which enhances immune defense in the gut has structural and functional properties similar to known superantigens. PMID:7615813

  9. Early life dynamics of the human gut virome and bacterial microbiome in infants

    PubMed Central

    Lim, Efrem S.; Zhou, Yanjiao; Zhao, Guoyan; Bauer, Irma K.; Droit, Lindsay; Ndao, I. Malick; Warner, Barbara B.; Tarr, Phillip I.; Wang, David; Holtz, Lori R.

    2016-01-01

    The early years of life are important for immune development and influences health in adulthood. While it has been established that the gut bacterial microbiome is rapidly acquired after birth, less is known about the viral microbiome (or, virome), consisting of bacteriophages and eukaryotic RNA and DNA viruses, during the first years of life. Here, we characterized the gut virome and bacterial microbiome in a longitudinal cohort of healthy infant twins. The virome and bacterial microbiome are more similar between co-twins than between non-related infants. From birth to two years of age, the eukaryotic virome and the bacterial microbiome expanded, but this was accompanied by a contraction of and shift in the bacteriophage virome composition. The bacteriophage-bacteria relationship begins from birth with a high predator-low prey dynamic, consistent with the Lotka-Volterra predator-prey model. Thus, in contrast to the stable microbiome observed in adults, the infant microbiome is highly dynamic and associated with early life changes in the composition of bacteria, viruses and bacteriophage with age. PMID:26366711

  10. Early life dynamics of the human gut virome and bacterial microbiome in infants.

    PubMed

    Lim, Efrem S; Zhou, Yanjiao; Zhao, Guoyan; Bauer, Irma K; Droit, Lindsay; Ndao, I Malick; Warner, Barbara B; Tarr, Phillip I; Wang, David; Holtz, Lori R

    2015-10-01

    The early years of life are important for immune development and influence health in adulthood. Although it has been established that the gut bacterial microbiome is rapidly acquired after birth, less is known about the viral microbiome (or 'virome'), consisting of bacteriophages and eukaryotic RNA and DNA viruses, during the first years of life. Here, we characterized the gut virome and bacterial microbiome in a longitudinal cohort of healthy infant twins. The virome and bacterial microbiome were more similar between co-twins than between unrelated infants. From birth to 2 years of age, the eukaryotic virome and the bacterial microbiome expanded, but this was accompanied by a contraction of and shift in the bacteriophage virome composition. The bacteriophage-bacteria relationship begins from birth with a high predator-low prey dynamic, consistent with the Lotka-Volterra prey model. Thus, in contrast to the stable microbiome observed in adults, the infant microbiome is highly dynamic and associated with early life changes in the composition of bacteria, viruses and bacteriophages with age. PMID:26366711

  11. The initial state of the human gut microbiome determines its reshaping by antibiotics.

    PubMed

    Raymond, Frédéric; Ouameur, Amin A; Déraspe, Maxime; Iqbal, Naeem; Gingras, Hélène; Dridi, Bédis; Leprohon, Philippe; Plante, Pier-Luc; Giroux, Richard; Bérubé, Ève; Frenette, Johanne; Boudreau, Dominique K; Simard, Jean-Luc; Chabot, Isabelle; Domingo, Marc-Christian; Trottier, Sylvie; Boissinot, Maurice; Huletsky, Ann; Roy, Paul H; Ouellette, Marc; Bergeron, Michel G; Corbeil, Jacques

    2016-03-01

    Microbiome studies have demonstrated the high inter-individual diversity of the gut microbiota. However, how the initial composition of the microbiome affects the impact of antibiotics on microbial communities is relatively unexplored. To specifically address this question, we administered a second-generation cephalosporin, cefprozil, to healthy volunteers. Stool samples gathered before antibiotic exposure, at the end of the treatment and 3 months later were analysed using shotgun metagenomic sequencing. On average, 15 billion nucleotides were sequenced for each sample. We show that standard antibiotic treatment can alter the gut microbiome in a specific, reproducible and predictable manner. The most consistent effect of the antibiotic was the increase of Lachnoclostridium bolteae in 16 out of the 18 cefprozil-exposed participants. Strikingly, we identified a subgroup of participants who were enriched in the opportunistic pathogen Enterobacter cloacae after exposure to the antibiotic, an effect linked to lower initial microbiome diversity and to a Bacteroides enterotype. Although the resistance gene content of participants' microbiomes was altered by the antibiotic, the impact of cefprozil remained specific to individual participants. Resistance genes that were not detectable prior to treatment were observed after a 7-day course of antibiotic administration. Specifically, point mutations in beta-lactamase blaCfxA-6 were enriched after antibiotic treatment in several participants. This suggests that monitoring the initial composition of the microbiome before treatment could assist in the prevention of some of the adverse effects associated with antibiotics or other treatments.

  12. Early life dynamics of the human gut virome and bacterial microbiome in infants.

    PubMed

    Lim, Efrem S; Zhou, Yanjiao; Zhao, Guoyan; Bauer, Irma K; Droit, Lindsay; Ndao, I Malick; Warner, Barbara B; Tarr, Phillip I; Wang, David; Holtz, Lori R

    2015-10-01

    The early years of life are important for immune development and influence health in adulthood. Although it has been established that the gut bacterial microbiome is rapidly acquired after birth, less is known about the viral microbiome (or 'virome'), consisting of bacteriophages and eukaryotic RNA and DNA viruses, during the first years of life. Here, we characterized the gut virome and bacterial microbiome in a longitudinal cohort of healthy infant twins. The virome and bacterial microbiome were more similar between co-twins than between unrelated infants. From birth to 2 years of age, the eukaryotic virome and the bacterial microbiome expanded, but this was accompanied by a contraction of and shift in the bacteriophage virome composition. The bacteriophage-bacteria relationship begins from birth with a high predator-low prey dynamic, consistent with the Lotka-Volterra prey model. Thus, in contrast to the stable microbiome observed in adults, the infant microbiome is highly dynamic and associated with early life changes in the composition of bacteria, viruses and bacteriophages with age.

  13. Gut microbiota and liver diseases

    PubMed Central

    Minemura, Masami; Shimizu, Yukihiro

    2015-01-01

    Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases. PMID:25684933

  14. Arabinoxylans and inulin differentially modulate the mucosal and luminal gut microbiota and mucin-degradation in humanized rats.

    PubMed

    Van den Abbeele, Pieter; Gérard, Philippe; Rabot, Sylvie; Bruneau, Aurélia; El Aidy, Sahar; Derrien, Muriel; Kleerebezem, Michiel; Zoetendal, Erwin G; Smidt, Hauke; Verstraete, Willy; Van de Wiele, Tom; Possemiers, Sam

    2011-10-01

    The endogenous gut microbiota affects the host in many ways. Prebiotics should favour beneficial intestinal microbes and thus improve host health. In this study, we investigated how a novel class of potential prebiotic long-chain arabinoxylans (LC-AX) and the well-established prebiotic inulin (IN) modulate the gut microbiota of humanized rats. Six weeks after axenic rats were inoculated with a human faecal microbiota, their colonic microbiota was similar to this inoculum (∼ 70%), whereas their caecal microbiota was enriched with Verrucomicrobia and Firmicutes concomitant with lower abundance of Bacteroidetes. Moreover, different Bifidobacterium species colonized the lumen (B. adolescentis) and mucus (B. longum and B. bifidum). Both LC-AX and IN increased SCFA levels and induced a shift from acetate towards health-promoting propionate and butyrate respectively. By applying a high-resolution phylogenetic micro-array (HITChip) at the site of fermentation (caecum), IN and LC-AX were shown to stimulate bacterial groups with known butyrate-producers (Roseburia intestinalis, Eubacterium rectale, Anaerostipes caccae) and bifidobacteria (B. longum) respectively. Prebiotic administration also resulted in lower caecal abundances of the mucin-degrading Akkermansia muciniphila and potentially more mucin production by the host. Both factors might explain the increased caecal mucin levels for LC-AX (threefold) and IN (sixfold). These mucins were degraded along the colon, resulting in high faecal abundances of Akkermansia muciniphila for LC-AX and especially IN-treated rats. Finally, the microbial changes caused an adaptation period for the host with less weight gain, after which the host fine-tuned the interaction with this altered microbiota. Our results demonstrate that next to IN, LC-AX are promising prebiotic compounds by stimulating production of health-promoting metabolites by specific microbes in the proximal regions. Further, prebiotic supplementation shifted mucin

  15. Minireview: Linking genetic variation in human Toll-like receptor 5 genes to the gut microbiome’s potential to cause inflammation

    PubMed Central

    Leifer, Cynthia A.; McConkey, Cameron; Li, Sha; Chassaing, Benoit; Gewirtz, Andrew T.; Ley, Ruth E.

    2014-01-01

    Immunodeficiencies can lead to alterations of the gut microbiome that render it pathogenic and capable of transmitting disease to naïve hosts. Here we review the role of Toll-like receptor (TLR) 5, the innate receptor for bacterial flagellin, in immune responses to the normal gut microbiota with a focus its role on adaptive immunity. Loss of TLR5 has profound effects on the microbiota that include greater temporal instability of major lineages and upregulation of flagellar motility genes that may be linked to the reduced levels of anti-flagellin antibodies in the TLR5−/− host. A variety of human TLR5 gene alleles exist that also associated with inflammatory conditions and may do so via effects on the gut microbiome and altered host-microbial crosstalk. PMID:25284610

  16. The human gut microbial ecology associated with overweight and obesity determines ellagic acid metabolism.

    PubMed

    Selma, María V; Romo-Vaquero, María; García-Villalba, Rocío; González-Sarrías, Antonio; Tomás-Barberán, Francisco A; Espín, Juan C

    2016-04-01

    We recently identified three metabotypes (0, A and B) that depend on the metabolic profile of urolithins produced from polyphenol ellagic acid (EA). The gut microbiota and Gordonibacter spp. recently were identified as species able to produce urolithins. A higher percentage of metabotype B was found in patients with metabolic syndrome or colorectal cancer in comparison with healthy individuals. The aim of the present study was to analyse differences in EA metabolism between healthy overweight-obese and normoweight individuals and evaluate the role of gut microbial composition including Gordonibacter. Although the three metabotypes were confirmed in both groups, metabotype B prevailed in overweight-obese (31%) versus normoweight (20%) individuals while metabotype A was higher in normoweight (70%) than the overweight-obese group (57%). This suggests that weight gain favours the growth of bacteria capable of producing urolithin B and/or isourolithin A with respect to urolithin A-producing bacteria. Gordonibacter spp. levels were not significantly different between normoweight and overweight-obese groups but higher Gordonibacter levels were found in metabotype A individuals than in those with metabotype B. Other bacterial species have been reported to show a much closer relationship to obesity and dysbiosis than Gordonibacter. However, Gordonibacter levels are negatively correlated with metabotype B, which prevails in metabolic syndrome and colorectal cancer. This is the first report that links overweight and obesity with an alteration in the catabolism of EA, and where the correlation of Gordonibacter to this alteration is shown. Future investigation of Gordonibacter and urolithin metabotypes as potential biomarkers or therapeutic targets of obesity-related diseases is warranted.

  17. Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model.

    PubMed

    Yu, Yueyue; Lu, Lei; Sun, Jun; Petrof, Elaine O; Claud, Erika C

    2016-09-01

    Development of the infant small intestine is influenced by bacterial colonization. To promote establishment of optimal microbial communities in preterm infants, knowledge of the beneficial functions of the early gut microbiota on intestinal development is needed. The purpose of this study was to investigate the impact of early preterm infant microbiota on host gut development using a gnotobiotic mouse model. Histological assessment of intestinal development was performed. The differentiation of four epithelial cell lineages (enterocytes, goblet cells, Paneth cells, enteroendocrine cells) and tight junction (TJ) formation was examined. Using weight gain as a surrogate marker for health, we found that early microbiota from a preterm infant with normal weight gain (MPI-H) induced increased villus height and crypt depth, increased cell proliferation, increased numbers of goblet cells and Paneth cells, and enhanced TJs compared with the changes induced by early microbiota from a poor weight gain preterm infant (MPI-L). Laser capture microdissection (LCM) plus qRT-PCR further revealed, in MPI-H mice, a higher expression of stem cell marker Lgr5 and Paneth cell markers Lyz1 and Cryptdin5 in crypt populations, along with higher expression of the goblet cell and mature enterocyte marker Muc3 in villus populations. In contrast, MPI-L microbiota failed to induce the aforementioned changes and presented intestinal characteristics comparable to a germ-free host. Our data demonstrate that microbial communities have differential effects on intestinal development. Future studies to identify pioneer settlers in neonatal microbial communities necessary to induce maturation may provide new insights for preterm infant microbial ecosystem therapeutics. PMID:27492329

  18. Impact of increasing fruit and vegetables and flavonoid intake on the human gut microbiota.

    PubMed

    Klinder, Annett; Shen, Qing; Heppel, Susanne; Lovegrove, Julie A; Rowland, Ian; Tuohy, Kieran M

    2016-04-01

    Epidemiological studies have shown protective effects of fruits and vegetables (F&V) in lowering the risk of developing cardiovascular diseases (CVD) and cancers. Plant-derived dietary fibre (non-digestible polysaccharides) and/or flavonoids may mediate the observed protective effects particularly through their interaction with the gut microbiota. The aim of this study was to assess the impact of fruit and vegetable (F&V) intake on gut microbiota, with an emphasis on the role of flavonoids, and further to explore relationships between microbiota and factors associated with CVD risk. In the study, a parallel design with 3 study groups, participants in the two intervention groups representing high-flavonoid (HF) and low flavonoid (LF) intakes were asked to increase their daily F&V intake by 2, 4 and 6 portions for a duration of 6 weeks each, while a third (control) group continued with their habitual diet. Faecal samples were collected at baseline and after each dose from 122 subjects. Faecal bacteria enumeration was performed by fluorescence in situ hybridisation (FISH). Correlations of dietary components, flavonoid intake and markers of CVD with bacterial numbers were also performed. A significant dose X treatment interaction was only found for Clostidium leptum-Ruminococcus bromii/flavefaciens with a significant increase after intake of 6 additional portions in the LF group. Correlation analysis of the data from all 122 subjects independent from dietary intervention indicated an inhibitory role of F&V intake, flavonoid content and sugars against the growth of potentially pathogenic clostridia. Additionally, we observed associations between certain bacterial populations and CVD risk factors including plasma TNF-α, plasma lipids and BMI/waist circumference. PMID:26757793

  19. Preterm infant gut microbiota affects intestinal epithelial development in a humanized microbiome gnotobiotic mouse model.

    PubMed

    Yu, Yueyue; Lu, Lei; Sun, Jun; Petrof, Elaine O; Claud, Erika C

    2016-09-01

    Development of the infant small intestine is influenced by bacterial colonization. To promote establishment of optimal microbial communities in preterm infants, knowledge of the beneficial functions of the early gut microbiota on intestinal development is needed. The purpose of this study was to investigate the impact of early preterm infant microbiota on host gut development using a gnotobiotic mouse model. Histological assessment of intestinal development was performed. The differentiation of four epithelial cell lineages (enterocytes, goblet cells, Paneth cells, enteroendocrine cells) and tight junction (TJ) formation was examined. Using weight gain as a surrogate marker for health, we found that early microbiota from a preterm infant with normal weight gain (MPI-H) induced increased villus height and crypt depth, increased cell proliferation, increased numbers of goblet cells and Paneth cells, and enhanced TJs compared with the changes induced by early microbiota from a poor weight gain preterm infant (MPI-L). Laser capture microdissection (LCM) plus qRT-PCR further revealed, in MPI-H mice, a higher expression of stem cell marker Lgr5 and Paneth cell markers Lyz1 and Cryptdin5 in crypt populations, along with higher expression of the goblet cell and mature enterocyte marker Muc3 in villus populations. In contrast, MPI-L microbiota failed to induce the aforementioned changes and presented intestinal characteristics comparable to a germ-free host. Our data demonstrate that microbial communities have differential effects on intestinal development. Future studies to identify pioneer settlers in neonatal microbial communities necessary to induce maturation may provide new insights for preterm infant microbial ecosystem therapeutics.

  20. Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut.

    PubMed

    Rivière, Audrey; Selak, Marija; Lantin, David; Leroy, Frédéric; De Vuyst, Luc

    2016-01-01

    With the increasing amount of evidence linking certain disorders of the human body to a disturbed gut microbiota, there is a growing interest for compounds that positively influence its composition and activity through diet. Besides the consumption of probiotics to stimulate favorable bacterial communities in the human gastrointestinal tract, prebiotics such as inulin-type fructans (ITF) and arabinoxylan-oligosaccharides (AXOS) can be consumed to increase the number of bifidobacteria in the colon. Several functions have been attributed to bifidobacteria, encompassing degradation of non-digestible carbohydrates, protection against pathogens, production of vitamin B, antioxidants, and conjugated linoleic acids, and stimulation of the immune system. During life, the numbers of bifidobacteria decrease from up to 90% of the total colon microbiota in vaginally delivered breast-fed infants to <5% in the colon of adults and they decrease even more in that of elderly as well as in patients with certain disorders such as antibiotic-associated diarrhea, inflammatory bowel disease, irritable bowel syndrome, obesity, allergies, and regressive autism. It has been suggested that the bifidogenic effects of ITF and AXOS are the result of strain-specific yet complementary carbohydrate degradation mechanisms within cooperating bifidobacterial consortia. Except for a bifidogenic effect, ITF and AXOS also have shown to cause a butyrogenic effect in the human colon, i.e., an enhancement of colon butyrate production. Butyrate is an essential metabolite in the human colon, as it is the preferred energy source for the colon epithelial cells, contributes to the maintenance of the gut barrier functions, and has immunomodulatory and anti-inflammatory properties. It has been shown that the butyrogenic effects of ITF and AXOS are the result of cross-feeding interactions between bifidobacteria and butyrate-producing colon bacteria, such as Faecalibacterium prausnitzii (clostridial cluster IV

  1. Bifidobacteria and Butyrate-Producing Colon Bacteria: Importance and Strategies for Their Stimulation in the Human Gut

    PubMed Central

    Rivière, Audrey; Selak, Marija; Lantin, David; Leroy, Frédéric; De Vuyst, Luc

    2016-01-01

    With the increasing amount of evidence linking certain disorders of the human body to a disturbed gut microbiota, there is a growing interest for compounds that positively influence its composition and activity through diet. Besides the consumption of probiotics to stimulate favorable bacterial communities in the human gastrointestinal tract, prebiotics such as inulin-type fructans (ITF) and arabinoxylan-oligosaccharides (AXOS) can be consumed to increase the number of bifidobacteria in the colon. Several functions have been attributed to bifidobacteria, encompassing degradation of non-digestible carbohydrates, protection against pathogens, production of vitamin B, antioxidants, and conjugated linoleic acids, and stimulation of the immune system. During life, the numbers of bifidobacteria decrease from up to 90% of the total colon microbiota in vaginally delivered breast-fed infants to <5% in the colon of adults and they decrease even more in that of elderly as well as in patients with certain disorders such as antibiotic-associated diarrhea, inflammatory bowel disease, irritable bowel syndrome, obesity, allergies, and regressive autism. It has been suggested that the bifidogenic effects of ITF and AXOS are the result of strain-specific yet complementary carbohydrate degradation mechanisms within cooperating bifidobacterial consortia. Except for a bifidogenic effect, ITF and AXOS also have shown to cause a butyrogenic effect in the human colon, i.e., an enhancement of colon butyrate production. Butyrate is an essential metabolite in the human colon, as it is the preferred energy source for the colon epithelial cells, contributes to the maintenance of the gut barrier functions, and has immunomodulatory and anti-inflammatory properties. It has been shown that the butyrogenic effects of ITF and AXOS are the result of cross-feeding interactions between bifidobacteria and butyrate-producing colon bacteria, such as Faecalibacterium prausnitzii (clostridial cluster IV

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

    PubMed Central

    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

  3. Anticancer Drugs from Marine Flora: An Overview

    PubMed Central

    Sithranga Boopathy, N.; Kathiresan, K.

    2010-01-01

    Marine floras, such as bacteria, actinobacteria, cyanobacteria, fungi, microalgae, seaweeds, mangroves, and other halophytes are extremely important oceanic resources, constituting over 90% of the oceanic biomass. They are taxonomically diverse, largely productive, biologically active, and chemically unique offering a great scope for discovery of new anticancer drugs. The marine floras are rich in medicinally potent chemicals predominantly belonging to polyphenols and sulphated polysaccharides. The chemicals have displayed an array of pharmacological properties especially antioxidant, immunostimulatory, and antitumour activities. The phytochemicals possibly activate macrophages, induce apoptosis, and prevent oxidative damage of DNA, thereby controlling carcinogenesis. In spite of vast resources enriched with chemicals, the marine floras are largely unexplored for anticancer lead compounds. Hence, this paper reviews the works so far conducted on this aspect with a view to provide a baseline information for promoting the marine flora-based anticancer research in the present context of increasing cancer incidence, deprived of the cheaper, safer, and potent medicines to challenge the dreadful human disease. PMID:21461373

  4. Study of the Aminoglycoside Subsistence Phenotype of Bacteria Residing in the Gut of Humans and Zoo Animals

    PubMed Central

    Bello González, Teresita de J.; Zuidema, Tina; Bor, Gerrit; Smidt, Hauke; van Passel, Mark W. J.

    2016-01-01

    Recent studies indicate that next to antibiotic resistance, bacteria are able to subsist on antibiotics as a carbon source. Here we evaluated the potential of gut bacteria from healthy human volunteers and zoo animals to subsist on antibiotics. Nine gut isolates of Escherichia coli and Cellulosimicrobium sp. displayed increases in colony forming units (CFU) during incubations in minimal medium with only antibiotics added, i.e., the antibiotic subsistence phenotype. Furthermore, laboratory strains of E. coli and Pseudomonas putida equipped with the aminoglycoside 3′ phosphotransferase II gene also displayed the subsistence phenotype on aminoglycosides. In order to address which endogenous genes could be involved in these subsistence phenotypes, the broad-range glycosyl-hydrolase inhibiting iminosugar deoxynojirimycin (DNJ) was used. Addition of DNJ to minimal medium containing glucose showed initial growth retardation of resistant E. coli, which was rapidly recovered to normal growth. In contrast, addition of DNJ to minimal medium containing kanamycin arrested resistant E. coli growth, suggesting that glycosyl-hydrolases were involved in the subsistence phenotype. However, antibiotic degradation experiments showed no reduction in kanamycin, even though the number of CFUs increased. Although antibiotic subsistence phenotypes are readily observed in bacterial species, and are even found in susceptible laboratory strains carrying standard resistance genes, we conclude there is a discrepancy between the observed antibiotic subsistence phenotype and actual antibiotic degradation. Based on these results we can hypothesize that aminoglycoside modifying enzymes might first inactivate the antibiotic (i.e., by acetylation of amino groups, modification of hydroxyl groups by adenylation and phosphorylation respectively), before the subsequent action of catabolic enzymes. Even though we do not dispute that antibiotics could be used as a single carbon source, our observations

  5. Study of the Aminoglycoside Subsistence Phenotype of Bacteria Residing in the Gut of Humans and Zoo Animals.

    PubMed

    Bello González, Teresita de J; Zuidema, Tina; Bor, Gerrit; Smidt, Hauke; van Passel, Mark W J

    2015-01-01

    Recent studies indicate that next to antibiotic resistance, bacteria are able to subsist on antibiotics as a carbon source. Here we evaluated the potential of gut bacteria from healthy human volunteers and zoo animals to subsist on antibiotics. Nine gut isolates of Escherichia coli and Cellulosimicrobium sp. displayed increases in colony forming units (CFU) during incubations in minimal medium with only antibiotics added, i.e., the antibiotic subsistence phenotype. Furthermore, laboratory strains of E. coli and Pseudomonas putida equipped with the aminoglycoside 3' phosphotransferase II gene also displayed the subsistence phenotype on aminoglycosides. In order to address which endogenous genes could be involved in these subsistence phenotypes, the broad-range glycosyl-hydrolase inhibiting iminosugar deoxynojirimycin (DNJ) was used. Addition of DNJ to minimal medium containing glucose showed initial growth retardation of resistant E. coli, which was rapidly recovered to normal growth. In contrast, addition of DNJ to minimal medium containing kanamycin arrested resistant E. coli growth, suggesting that glycosyl-hydrolases were involved in the subsistence phenotype. However, antibiotic degradation experiments showed no reduction in kanamycin, even though the number of CFUs increased. Although antibiotic subsistence phenotypes are readily observed in bacterial species, and are even found in susceptible laboratory strains carrying standard resistance genes, we conclude there is a discrepancy between the observed antibiotic subsistence phenotype and actual antibiotic degradation. Based on these results we can hypothesize that aminoglycoside modifying enzymes might first inactivate the antibiotic (i.e., by acetylation of amino groups, modification of hydroxyl groups by adenylation and phosphorylation respectively), before the subsequent action of catabolic enzymes. Even though we do not dispute that antibiotics could be used as a single carbon source, our observations

  6. A galectin-specific signature in the gut delineates Crohn's disease and ulcerative colitis from other human inflammatory intestinal disorders.

    PubMed

    Papa Gobbi, Rodrigo; De Francesco, Nicolás; Bondar, Constanza; Muglia, Cecilia; Chirdo, Fernando; Rumbo, Martín; Rocca, Andrés; Toscano, Marta A; Sambuelli, Alicia; Rabinovich, Gabriel A; Docena, Guillermo H

    2016-01-01

    Inflammatory bowel diseases (IBD) are chronic and relapsing inflammatory conditions of the gastrointestinal tract including Crohn's disease (CD) and ulcerative colitis (UC). Galectins, defined by shared consensus amino acid sequence and affinity for β-galactosides, are critical modulators of the inflammatory response. However, the relevance of the galectin network in the pathogenesis of human IBD has not yet been explored. Here, we analyzed the expression of relevant members of the galectin family in intestinal biopsies, and identified their contribution as novel mucosal markers in IBD. Colonic biopsies were obtained from 59 IBD patients (22 CD and 37 UC), 9 patients with gut rejection after transplantation, 8 adult celiac patients, and 32 non-IBD donors. Galectin mRNA expression was analyzed by RT-PCR and qPCR using specific primers for individual galectins. A linear discriminant analysis (LDA) was used to analyze galectin expression in individual intestinal samples. Expression of common mucosal-associated galectins (Gal-1, -3, -4, -9) is dysregulated in inflamed tissues of IBD patients compared with non-inflamed IBD or control samples. LDA discriminated between different inflammation grades in active IBD and showed that remission IBD samples were clusterized with control samples. Galectin profiling could not distinguish CD and UC. Furthermore, inflamed IBD was discriminated from inflamed tissue of rejected gut in transplanted patients and duodenum of celiac patients, which could not be distinguished from control duodenum samples. The integrative analysis of galectins discriminated IBD from other intestinal inflammatory conditions and could be used as potential mucosal biomarker.

  7. Influence of H7N9 virus infection and associated treatment on human gut microbiota

    PubMed Central

    Qin, Nan; Zheng, Beiwen; Yao, Jian; Guo, Lihua; Zuo, Jian; Wu, Lingjiao; Zhou, Jiawei; Liu, Lin; Guo, Jing; Ni, Shujun; Li, Ang; Zhu, Yixin; Liang, Weifeng; Xiao, Yonghong; Ehrlich, S. Dusko; Li, Lanjuan

    2015-01-01

    Between March and June, 2013, forty H7N9 patients were hospitalized in our hospital. Next-generation sequencing technologies have been used to sequence the fecal DNA samples of the patient, the within sample diversity analysis, enterotyping, functional gene and metagenomic species analysis have been carried on both the patients and healthy controls. The influence of associated treatment in H7N9 infected patients is dramatic and was firstly revealed in species level due to deep sequencing technology. We found that most of the MetaGenomic Species (MGS) enriched in the control samples were Roseburia inulinivorans DSM 16841, butyrate producing bacterium SS3/4 and most of MGS enriched in the H7N9 patients were Clostridium sp. 7 2 43FAA and Enterococcus faecium. It was concluded that H7N9 viral infection and antibiotic administration have a significant effect on the microbiota community with decreased diversity and overgrowth of the bacteria such as Escherichia coli and Enterococcus faecium. Enterotype analysis showed that the communities were unstable. Treatment including antivirals, probiotics and antibiotics helps to improve the microbiota diversity and the abundance of beneficial bacteria in the gut. PMID:26490635

  8. Recent advances in the role of probiotics in human inflammation and gut health.

    PubMed

    Rupa, Prithy; Mine, Yoshinori

    2012-08-29

    The gastrointestinal (GI) tract provides residence to an astounding number of bacterial species, which have profound effects on host biology, function, physiology, and immune response. Discovery of "symbiosis factors" from symbionts that facilitate the peaceful coexistence of microbiota and the host immune system are of interest. Symbionts synthesize immunomodulatory molecules that guide maturation of the immune system and have pivotal roles in many biological processes; however, individuals differ in the makeup of their GI microbiota, which is influenced by many external and internal factors such as diet, antibiotic use, and host genetics, which in turn influences health and disease outcomes. Various endogenous, genetic, and environmental factors influence GI development including species composition and health status of neonates, resulting in interactions that occur between the bacteria and the host. Mechanisms of probiotics involved in homeostasis of a balanced immune system have been inconclusive. The probable mechanism of action may be postulated as direct competition between pathogenic bacteria in the gut and/or immune modulation. This review focuses on probiotics in health and disease prevention, especially the biological importance of intestinal regulation of inflammatory processes that may be beneficial in a multitude of disorders both inside and outside the GI tract.

  9. Recent advances in the role of probiotics in human inflammation and gut health.

    PubMed

    Rupa, Prithy; Mine, Yoshinori

    2012-08-29

    The gastrointestinal (GI) tract provides residence to an astounding number of bacterial species, which have profound effects on host biology, function, physiology, and immune response. Discovery of "symbiosis factors" from symbionts that facilitate the peaceful coexistence of microbiota and the host immune system are of interest. Symbionts synthesize immunomodulatory molecules that guide maturation of the immune system and have pivotal roles in many biological processes; however, individuals differ in the makeup of their GI microbiota, which is influenced by many external and internal factors such as diet, antibiotic use, and host genetics, which in turn influences health and disease outcomes. Various endogenous, genetic, and environmental factors influence GI development including species composition and health status of neonates, resulting in interactions that occur between the bacteria and the host. Mechanisms of probiotics involved in homeostasis of a balanced immune system have been inconclusive. The probable mechanism of action may be postulated as direct competition between pathogenic bacteria in the gut and/or immune modulation. This review focuses on probiotics in health and disease prevention, especially the biological importance of intestinal regulation of inflammatory processes that may be beneficial in a multitude of disorders both inside and outside the GI tract. PMID:22897745

  10. Villification of the gut

    NASA Astrophysics Data System (ADS)

    Tallinen, Tuomas; Shyer, Amy E.; Tabin, Clifford J.; Mahadevan, L.

    2014-03-01

    The villi of the human and chick gut are formed in similar stepwise progressions, wherein the mesenchyme and attached epithelium first fold into longitudinal ridges, then a zigzag pattern, and lastly individual villi. We combine biological manipulations and quantitative modeling to show that these steps of villification depend on the sequential differentiation of the distinct smooth muscle layers of the gut, which restrict the expansion of the growing endoderm and mesenchyme, generating compressive stresses that lead to their buckling and folding. Our computational model incorporates measured elastic properties and growth rates in the developing gut, recapitulating the morphological patterns seen during villification in a variety of species. Our study provides a mechanical basis for the genesis of these epithelial protrusions that are essential for providing sufficient surface area for nutrient absorption.

  11. Gut microbiota and allogeneic transplantation.

    PubMed

    Wang, Weilin; Xu, Shaoyan; Ren, Zhigang; Jiang, Jianwen; Zheng, Shusen

    2015-08-23

    The latest high-throughput sequencing technologies show that there are more than 1000 types of microbiota in the human gut. These microbes are not only important to maintain human health, but also closely related to the occurrence and development of various diseases. With the development of transplantation technologies, allogeneic transplantation has become an effective therapy for a variety of end-stage diseases. However, complications after transplantation still restrict its further development. Post-transplantation complications are closely associated with a host's immune system. There is also an interaction between a person's gut microbiota and immune system. Recently, animal and human studies have shown that gut microbial populations and diversity are altered after allogeneic transplantations, such as liver transplantation (LT), small bowel transplantation (SBT), kidney transplantation (KT) and hematopoietic stem cell transplantation (HTCT). Moreover, when complications, such as infection, rejection and graft versus host disease (GVHD) occur, gut microbial populations and diversity present a significant dysbiosis. Several animal and clinical studies have demonstrated that taking probiotics and prebiotics can effectively regulate gut microbiota and reduce the incidence of complications after transplantation. However, the role of intestinal decontamination in allogeneic transplantation is controversial. This paper reviews gut microbial status after transplantation and its relationship with complications. The role of intervention methods, including antibiotics, probiotics and prebiotics, in complications after transplantation are also discussed. Further research in this new field needs to determine the definite relationship between gut microbial dysbiosis and complications after transplantation. Additionally, further research examining gut microbial intervention methods to ameliorate complications after transplantation is warranted. A better understanding of the

  12. Colorectal Cancer and the Human Gut Microbiome: Reproducibility with Whole-Genome Shotgun Sequencing

    PubMed Central

    Hua, Xing; Zeller, Georg; Sunagawa, Shinichi; Voigt, Anita Y.; Hercog, Rajna; Goedert, James J.; Shi, Jianxin; Bork, Peer; Sinha, Rashmi

    2016-01-01

    Accumulating evidence indicates that the gut microbiota affects colorectal cancer development, but previous studies have varied in population, technical methods, and associations with cancer. Understanding these variations is needed for comparisons and for potential pooling across studies. Therefore, we performed whole-genome shotgun sequencing on fecal samples from 52 pre-treatment colorectal cancer cases and 52 matched controls from Washington, DC. We compared findings from a previously published 16S rRNA study to the metagenomics-derived taxonomy within the same population. In addition, metagenome-predicted genes, modules, and pathways in the Washington, DC cases and controls were compared to cases and controls recruited in France whose specimens were processed using the same platform. Associations between the presence of fecal Fusobacteria, Fusobacterium, and Porphyromonas with colorectal cancer detected by 16S rRNA were reproduced by metagenomics, whereas higher relative abundance of Clostridia in cancer cases based on 16S rRNA was merely borderline based on metagenomics. This demonstrated that within the same sample set, most, but not all taxonomic associations were seen with both methods. Considering significant cancer associations with the relative abundance of genes, modules, and pathways in a recently published French metagenomics dataset, statistically significant associations in the Washington, DC population were detected for four out of 10 genes, three out of nine modules, and seven out of 17 pathways. In total, colorectal cancer status in the Washington, DC study was associated with 39% of the metagenome-predicted genes, modules, and pathways identified in the French study. More within and between population comparisons are needed to identify sources of variation and disease associations that can be reproduced despite these variations. Future studies should have larger sample sizes or pool data across studies to have sufficient power to detect

  13. MALDI-TOF Identification of the Human Gut Microbiome in People with and without Diarrhea in Senegal

    PubMed Central

    Samb-Ba, Bissoume; Mazenot, Catherine; Gassama-Sow, Amy; Dubourg, Grégory; Richet, Hervé; Hugon, Perrine; Lagier, Jean-Christophe; Raoult, Didier; Fenollar, Florence

    2014-01-01

    Background In Africa, there are several problems with the specific identification of bacteria. Recently, MALDI-TOF mass spectrometry has become a powerful tool for the routine microbial identification in many clinical laboratories. Methodology/Principal Findings This study was conducted using feces from 347 individuals (162 with diarrhea and 185 without diarrhea) sampled in health centers in Dakar, Senegal. Feces were transported from Dakar to Marseille, France, where they were cultured using different culture conditions. The isolated colonies were identified using MALDI-TOF. If a colony was unidentified, 16S rRNA sequencing was performed. Overall, 2,753 isolates were tested, allowing for the identification of 189 bacteria from 5 phyla, including 2 previously unknown species, 11 species not previously reported in the human gut, 10 species not previously reported in humans, and 3 fungi. 2,718 bacterial isolates (98.8%) out of 2,750 yielded an accurate identification using mass spectrometry, as did the 3 Candida albicans isolates. Thirty-two bacterial isolates not identified by MALDI-TOF (1.2%) were identified by sequencing, allowing for the identification of 2 new species. The number of bacterial species per fecal sample was significantly higher among patients without diarrhea (8.6±3) than in those with diarrhea (7.3±3.4; P = 0.0003). A modification of the gut microbiota was observed between the two groups. In individuals with diarrhea, major commensal bacterial species such as E. coli were significantly decreased (85% versus 64%), as were several Enterococcus spp. (E. faecium and E. casseliflavus) and anaerobes, such as Bacteroides spp. (B. uniformis and B. vulgatus) and Clostridium spp. (C. bifermentans, C. orbiscindens, C. perfringens, and C. symbosium). Conversely, several Bacillus spp. (B. licheniformis, B. mojavensis, and B. pumilus) were significantly more frequent among patients with diarrhea. Conclusions/Significance MALDI-TOF is a potentially

  14. [Role of intestinal flora in inflammatory bowel disease and probiotics place in their management].

    PubMed

    Belkahla, Néziha; Maamouri, Nadia; Ouerghi, Hajer; Ben Ammar, Ahmed

    2005-03-01

    The pathogenic role of certain microorganism of intestinal flora has been demonstrated in experimental colitis in animals and strongly suspected in inflammatory bowel disease in human, especially in Crohn's disease and pouchitis. Probiotics are living non pathogenic microorganisms that, upon oral ingestion exert benefits on human health by modulating enteric flora or by stimulation of local immune system. The aim of this article is to remind the role of intestinal flora in inflammatory bowel disease, the mechanism of inflammation induced by this flora and to review through the literature, the different clinical studies performed with probiotics in human.

  15. CHARACTERIZATION OF MICROBIAL GUT FLORA OF HETEROPTEROUS INSECTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many insects harbor a robust complement of prokaryotes in their alimentary canals. These microorganisms may facilitate nutrient availability and utilization, detoxification of environmental toxins, or play other important roles in the insect's life history. Understanding insect-microorganism inter...

  16. Food and human gut as reservoirs of transferable antibiotic resistance encoding genes

    PubMed Central

    Rolain, Jean-Marc

    2013-01-01

    The increase and spread of antibiotic resistance (AR) over the past decade in human pathogens has become a worldwide health concern. Recent genomic and metagenomic studies in humans, animals, in food and in the environment have led to the discovery of a huge reservoir of AR genes called the resistome that could be mobilized and transferred from these sources to human pathogens. AR is a natural phenomenon developed by bacteria to protect antibiotic-producing bacteria from their own products and also to increase their survival in highly competitive microbial environments. Although antibiotics are used extensively in humans and animals, there is also considerable usage of antibiotics in agriculture, especially in animal feeds and aquaculture. The aim of this review is to give an overview of the sources of AR and the use of antibiotics in these reservoirs as selectors for emergence of AR bacteria in humans via the food chain. PMID:23805136

  17. Strand-specific community RNA-seq reveals prevalent and dynamic antisense transcription in human gut microbiota

    PubMed Central

    Bao, Guanhui; Wang, Mingjie; Doak, Thomas G.; Ye, Yuzhen

    2015-01-01

    Metagenomics and other meta-omics approaches (including metatranscriptomics) provide insights into the composition and function of microbial communities living in different environments or animal hosts. Metatranscriptomics research provides an unprecedented opportunity to examine gene regulation for many microbial species simultaneously, and more importantly, for the majority that are unculturable microbial species, in their natural environments (or hosts). Current analyses of metatranscriptomic datasets focus on the detection of gene expression levels and the study of the relationship between changes of gene expression and changes of environment. As a demonstration of utilizing metatranscriptomics beyond these common analyses, we developed a computational and statistical procedure to analyze the antisense transcripts in strand-specific metatranscriptomic datasets. Antisense RNAs encoded on the DNA strand opposite a gene’s CDS have the potential to form extensive base-pairing interactions with the corresponding sense RNA, and can have important regulatory functions. Most studies of antisense RNAs in bacteria are rather recent, are mostly based on transcriptome analysis, and have been applied mainly to single bacterial species. Application of our approaches to human gut-associated metatranscriptomic datasets allowed us to survey antisense transcription for a large number of bacterial species associated with human beings. The ratio of protein coding genes with antisense transcription ranges from 0 to 35.8% (median = 10.0%) among 47 species. Our results show that antisense transcription is dynamic, varying between human individuals. Functional enrichment analysis revealed a preference of certain gene functions for antisense transcription, and transposase genes are among the most prominent ones (but we also observed antisense transcription in bacterial house-keeping genes). PMID:26388849

  18. Cospeciation of gut microbiota with hominids.

    PubMed

    Moeller, Andrew H; Caro-Quintero, Alejandro; Mjungu, Deus; Georgiev, Alexander V; Lonsdorf, Elizabeth V; Muller, Martin N; Pusey, Anne E; Peeters, Martine; Hahn, Beatrice H; Ochman, Howard

    2016-07-22

    The evolutionary origins of the bacterial lineages that populate the human gut are unknown. Here we show that multiple lineages of the predominant bacterial taxa in the gut arose via cospeciation with humans, chimpanzees, bonobos, and gorillas over the past 15 million years. Analyses of strain-level bacterial diversity within hominid gut microbiomes revealed that clades of Bacteroidaceae and Bifidobacteriaceae have been maintained exclusively within host lineages across hundreds of thousands of host generations. Divergence times of these cospeciating gut bacteria are congruent with those of hominids, indicating that nuclear, mitochondrial, and gut bacterial genomes diversified in concert during hominid evolution. This study identifies human gut bacteria descended from ancient symbionts that speciated simultaneously with humans and the African apes. PMID:27463672

  19. Cospeciation of gut microbiota with hominids.

    PubMed

    Moeller, Andrew H; Caro-Quintero, Alejandro; Mjungu, Deus; Georgiev, Alexander V; Lonsdorf, Elizabeth V; Muller, Martin N; Pusey, Anne E; Peeters, Martine; Hahn, Beatrice H; Ochman, Howard

    2016-07-22

    The evolutionary origins of the bacterial lineages that populate the human gut are unknown. Here we show that multiple lineages of the predominant bacterial taxa in the gut arose via cospeciation with humans, chimpanzees, bonobos, and gorillas over the past 15 million years. Analyses of strain-level bacterial diversity within hominid gut microbiomes revealed that clades of Bacteroidaceae and Bifidobacteriaceae have been maintained exclusively within host lineages across hundreds of thousands of host generations. Divergence times of these cospeciating gut bacteria are congruent with those of hominids, indicating that nuclear, mitochondrial, and gut bacterial genomes diversified in concert during hominid evolution. This study identifies human gut bacteria descended from ancient symbionts that speciated simultaneously with humans and the African apes.

  20. Crystal structure and activity studies of the C11 cysteine peptidase from Parabacteroides merdae in the human gut microbiome

    DOE PAGES

    McLuskey, Karen; Grewal, Jaspreet S.; Das, Debanu; Godzik, Adam; Lesley, Scott A.; Deacon, Ashley M.; Coombs, Graham H.; Elsliger, Marc-André; Wilson, Ian A.; Mottram, Jeremy C.

    2016-03-03

    Clan CD cysteine peptidases, a structurally related group of peptidases that include mammalian caspases, exhibit a wide range of important functions, along with a variety of specificities and activation mechanisms. However, for the clostripain family (denoted C11), little is currently known. Here, we describe the first crystal structure of a C11 protein from the human gut bacterium, Parabacteroides merdae (PmC11), determined to 1.7-Å resolution. PmC11 is a monomeric cysteine peptidase that comprises an extended caspase-like α/β/α sandwich and an unusual C-terminal domain. It shares core structural elements with clan CD cysteine peptidases but otherwise structurally differs from the other familiesmore » in the clan. These studies also revealed a well ordered break in the polypeptide chain at Lys147, resulting in a large conformational rearrangement close to the active site. Biochemical and kinetic analysis revealed Lys147 to be an intramolecular processing site at which cleavage is required for full activation of the enzyme, suggesting an autoinhibitory mechanism for self-preservation. PmC11 has an acidic binding pocket and a preference for basic substrates, and accepts substrates with Arg and Lys in P1 and does not require Ca2+ for activity. Altogether, these data provide insights into the mechanism and activity of PmC11 and a detailed framework for studies on C11 peptidases from other phylogenetic kingdoms.« less

  1. The human gut and groundwater harbor non-photosynthetic bacteria belonging to a new candidate phylum sibling to Cyanobacteria.

    PubMed

    Di Rienzi, Sara C; Sharon, Itai; Wrighton, Kelly C; Koren, Omry; Hug, Laura A; Thomas, Brian C; Goodrich, Julia K; Bell, Jordana T; Spector, Timothy D; Banfield, Jillian F; Ley, Ruth E

    2013-10-01

    Cyanobacteria were responsible for the oxygenation of the ancient atmosphere; however, the evolution of this phylum is enigmatic, as relatives have not been characterized. Here we use whole genome reconstruction of human fecal and subsurface aquifer metagenomic samples to obtain complete genomes for members of a new candidate phylum sibling to Cyanobacteria, for which we propose the designation 'Melainabacteria'. Metabolic analysis suggests that the ancestors to both lineages were non-photosynthetic, anaerobic, motile, and obligately fermentative. Cyanobacterial light sensing may have been facilitated by regulators present in the ancestor of these lineages. The subsurface organism has the capacity for nitrogen fixation using a nitrogenase distinct from that in Cyanobacteria, suggesting nitrogen fixation evolved separately in the two lineages. We hypothesize that Cyanobacteria split from Melainabacteria prior or due to the acquisition of oxygenic photosynthesis. Melainabacteria remained in anoxic zones and differentiated by niche adaptation, including for symbiosis in the mammalian gut. DOI:http://dx.doi.org/10.7554/eLife.01102.001.

  2. Crystal Structure and Activity Studies of the C11 Cysteine Peptidase from Parabacteroides merdae in the Human Gut Microbiome*

    PubMed Central

    Das, Debanu; Godzik, Adam; Lesley, Scott A.; Deacon, Ashley M.; Coombs, Graham H.; Elsliger, Marc-André; Wilson, Ian A.

    2016-01-01

    Clan CD cysteine peptidases, a structurally related group of peptidases that include mammalian caspases, exhibit a wide range of important functions, along with a variety of specificities and activation mechanisms. However, for the clostripain family (denoted C11), little is currently known. Here, we describe the first crystal structure of a C11 protein from the human gut bacterium, Parabacteroides merdae (PmC11), determined to 1.7-Å resolution. PmC11 is a monomeric cysteine peptidase that comprises an extended caspase-like α/β/α sandwich and an unusual C-terminal domain. It shares core structural elements with clan CD cysteine peptidases but otherwise structurally differs from the other families in the clan. These studies also revealed a well ordered break in the polypeptide chain at Lys147, resulting in a large conformational rearrangement close to the active site. Biochemical and kinetic analysis revealed Lys147 to be an intramolecular processing site at which cleavage is required for full activation of the enzyme, suggesting an autoinhibitory mechanism for self-preservation. PmC11 has an acidic binding pocket and a preference for basic substrates, and accepts substrates with Arg and Lys in P1 and does not require Ca2+ for activity. Collectively, these data provide insights into the mechanism and activity of PmC11 and a detailed framework for studies on C11 peptidases from other phylogenetic kingdoms. PMID:26940874

  3. Crystal Structure and Activity Studies of the C11 Cysteine Peptidase from Parabacteroides merdae in the Human Gut Microbiome.

    PubMed

    McLuskey, Karen; Grewal, Jaspreet S; Das, Debanu; Godzik, Adam; Lesley, Scott A; Deacon, Ashley M; Coombs, Graham H; Elsliger, Marc-André; Wilson, Ian A; Mottram, Jeremy C

    2016-04-29

    Clan CD cysteine peptidases, a structurally related group of peptidases that include mammalian caspases, exhibit a wide range of important functions, along with a variety of specificities and activation mechanisms. However, for the clostripain family (denoted C11), little is currently known. Here, we describe the first crystal structure of a C11 protein from the human gut bacterium, Parabacteroides merdae (PmC11), determined to 1.7-Å resolution. PmC11 is a monomeric cysteine peptidase that comprises an extended caspase-like α/β/α sandwich and an unusual C-terminal domain. It shares core structural elements with clan CD cysteine peptidases but otherwise structurally differs from the other families in the clan. These studies also revealed a well ordered break in the polypeptide chain at Lys(147), resulting in a large conformational rearrangement close to the active site. Biochemical and kinetic analysis revealed Lys(147) to be an intramolecular processing site at which cleavage is required for full activation of the enzyme, suggesting an autoinhibitory mechanism for self-preservation. PmC11 has an acidic binding pocket and a preference for basic substrates, and accepts substrates with Arg and Lys in P1 and does not require Ca(2+) for activity. Collectively, these data provide insights into the mechanism and activity of PmC11 and a detailed framework for studies on C11 peptidases from other phylogenetic kingdoms. PMID:26940874

  4. The human gut and groundwater harbor non-photosynthetic bacteria belonging to a new candidate phylum sibling to Cyanobacteria

    PubMed Central

    Di Rienzi, Sara C; Sharon, Itai; Wrighton, Kelly C; Koren, Omry; Hug, Laura A; Thomas, Brian C; Goodrich, Julia K; Bell, Jordana T; Spector, Timothy D; Banfield, Jillian F; Ley, Ruth E

    2013-01-01

    Cyanobacteria were responsible for the oxygenation of the ancient atmosphere; however, the evolution of this phylum is enigmatic, as relatives have not been characterized. Here we use whole genome reconstruction of human fecal and subsurface aquifer metagenomic samples to obtain complete genomes for members of a new candidate phylum sibling to Cyanobacteria, for which we propose the designation ‘Melainabacteria’. Metabolic analysis suggests that the ancestors to both lineages were non-photosynthetic, anaerobic, motile, and obligately fermentative. Cyanobacterial light sensing may have been facilitated by regulators present in the ancestor of these lineages. The subsurface organism has the capacity for nitrogen fixation using a nitrogenase distinct from that in Cyanobacteria, suggesting nitrogen fixation evolved separately in the two lineages. We hypothesize that Cyanobacteria split from Melainabacteria prior or due to the acquisition of oxygenic photosynthesis. Melainabacteria remained in anoxic zones and differentiated by niche adaptation, including for symbiosis in the mammalian gut. DOI: http://dx.doi.org/10.7554/eLife.01102.001 PMID:24137540

  5. The human gut microbiome in health: establishment and resilience of microbiota over a lifetime.

    PubMed

    Greenhalgh, Kacy; Meyer, Kristen M; Aagaard, Kjersti M; Wilmes, Paul

    2016-07-01

    With technological advances in culture-independent molecular methods, we are uncovering a new facet of our natural history by accounting for the vast diversity of microbial life which colonizes the human body. The human microbiome contributes functional genes and metabolites which affect human physiology and are, therefore, considered an important factor for maintaining health. Much has been described in the past decade based primarily on 16S rRNA gene amplicon sequencing regarding the diversity, structure, stability and dynamics of human microbiota in their various body habitats, most notably within the gastrointestinal tract (GIT). Relatively high levels of variation have been described across different stages of life and geographical locations for the GIT microbiome. These observations may prove helpful for the future contextualization of patterns in other body habitats especially in relation to identifying generalizable trends over human lifetime. Given the large degree of complexity and variability, a key challenge will be how to define baseline healthy microbiomes and how to identify features which reflect deviations therefrom in the future. In this context, metagenomics and functional omics will likely play a central role as they will allow resolution of microbiome-conferred functionalities associated with health. Such information will be vital for formulating therapeutic interventions aimed at managing microbiota-mediated health particularly in the GIT over the course of a human lifetime. PMID:27059297

  6. The human gut microbiome in health: establishment and resilience of microbiota over a lifetime.

    PubMed

    Greenhalgh, Kacy; Meyer, Kristen M; Aagaard, Kjersti M; Wilmes, Paul

    2016-07-01

    With technological advances in culture-independent molecular methods, we are uncovering a new facet of our natural history by accounting for the vast diversity of microbial life which colonizes the human body. The human microbiome contributes functional genes and metabolites which affect human physiology and are, therefore, considered an important factor for maintaining health. Much has been described in the past decade based primarily on 16S rRNA gene amplicon sequencing regarding the diversity, structure, stability and dynamics of human microbiota in their various body habitats, most notably within the gastrointestinal tract (GIT). Relatively high levels of variation have been described across different stages of life and geographical locations for the GIT microbiome. These observations may prove helpful for the future contextualization of patterns in other body habitats especially in relation to identifying generalizable trends over human lifetime. Given the large degree of complexity and variability, a key challenge will be how to define baseline healthy microbiomes and how to identify features which reflect deviations therefrom in the future. In this context, metagenomics and functional omics will likely play a central role as they will allow resolution of microbiome-conferred functionalities associated with health. Such information will be vital for formulating therapeutic interventions aimed at managing microbiota-mediated health particularly in the GIT over the course of a human lifetime.

  7. Dynamic In Vitro Models of the Human Gastrointestinal Tract as Relevant Tools to Assess the Survival of Probiotic Strains and Their Interactions with Gut Microbiota

    PubMed Central

    Cordonnier, Charlotte; Thévenot, Jonathan; Etienne-Mesmin, Lucie; Denis, Sylvain; Alric, Monique; Livrelli, Valérie; Blanquet-Diot, Stéphanie

    2015-01-01

    The beneficial effects of probiotics are conditioned by their survival during passage through the human gastrointestinal tract and their ability to favorably influence gut microbiota. The main objective of this study was to use dynamic in vitro models of the human digestive tract to investigate the effect of fasted or fed state on the survival kinetics of the new probiotic Saccharomyces cerevisiae strain CNCM I-3856 and to assess its influence on intestinal microbiota composition and activity. The probiotic yeast showed a high survival rate in the upper gastrointestinal tract whatever the route of admistration, i.e., within a glass of water or a Western-type meal. S. cerevisiae CNCM I-3856 was more sensitive to colonic conditions, as the strain was not able to colonize within the bioreactor despite a twice daily administration. The main bacterial populations of the gut microbiota, as well as the production of short chain fatty acids were not influenced by the probiotic treatment. However, the effect of the probiotic on the gut microbiota was found to be individual dependent. This study shows that dynamic in vitro models can be advantageously used to provide useful insight into the behavior of probiotic strains in the human digestive environment.

  8. Dynamic In Vitro Models of the Human Gastrointestinal Tract as Relevant Tools to Assess the Survival of Probiotic Strains and Their Interactions with Gut Microbiota

    PubMed Central

    Cordonnier, Charlotte; Thévenot, Jonathan; Etienne-Mesmin, Lucie; Denis, Sylvain; Alric, Monique; Livrelli, Valérie; Blanquet-Diot, Stéphanie

    2015-01-01

    The beneficial effects of probiotics are conditioned by their survival during passage through the human gastrointestinal tract and their ability to favorably influence gut microbiota. The main objective of this study was to use dynamic in vitro models of the human digestive tract to investigate the effect of fasted or fed state on the survival kinetics of the new probiotic Saccharomyces cerevisiae strain CNCM I-3856 and to assess its influence on intestinal microbiota composition and activity. The probiotic yeast showed a high survival rate in the upper gastrointestinal tract whatever the route of admistration, i.e., within a glass of water or a Western-type meal. S. cerevisiae CNCM I-3856 was more sensitive to colonic conditions, as the strain was not able to colonize within the bioreactor despite a twice daily administration. The main bacterial populations of the gut microbiota, as well as the production of short chain fatty acids were not influenced by the probiotic treatment. However, the effect of the probiotic on the gut microbiota was found to be individual dependent. This study shows that dynamic in vitro models can be advantageously used to provide useful insight into the behavior of probiotic strains in the human digestive environment. PMID:27682114

  9. Human gut Bacteroidetes can utilize yeast mannan through a selfish mechanism

    PubMed Central

    Zhu, Yanping; Cameron, Elizabeth; Pudlo, Nicholas A.; Porter, Nathan T.; Urs, Karthik; Thompson, Andrew J.; Cartmell, Alan; Rogowski, Artur; Hamilton, Brian S.; Chen, Rui; Tolbert, Thomas J.; Piens, Kathleen; Bracke, Debby; Vervecken, Wouter; Hakki, Zalihe; Speciale, Gaetano; Munōz-Munōz, Jose L.; Day, Andrew; Peña, Maria J.; McLean, Richard; Suits, Michael D.; Boraston, Alisdair B.; Atherly, Todd; Ziemer, Cherie J.; Williams, Spencer J.; Davies, Gideon J.; Abbott, D. Wade; Martens, Eric C.; Gilbert, Harry J.

    2016-01-01

    Yeasts, which have been a component of the human diet for at least 7000 years, possess an elaborate cell wall α-mannan. The influence of yeast mannan on the ecology of the human microbiota is unknown. Here we show that yeast α-mannan is a viable food source for Bacteroides thetaiotaomicron (Bt), a dominant member of the microbiota. Detailed biochemical analysis and targeted gene disruption studies support a model whereby limited cleavage of α-mannan on the surface generates large oligosaccharides that are subsequently depolymerized to mannose by the action of periplasmic enzymes. Co-culturing studies showed that metabolism of yeast mannan by Bt presents a ‘selfish’ model for the catabolism of this recalcitrant polysaccharide. This report shows how a cohort of highly successful members of the microbiota has evolved to consume sterically-restricted yeast glycans, an adaptation that may reflect the incorporation of eukaryotic microorganisms into the human diet. PMID:25567280

  10. A Prebiotic Formula Improves the Gastrointestinal Bacterial Flora in Toddlers

    PubMed Central

    Chen, Ya-Ling; Liao, Fang-Hsuean

    2016-01-01

    We aimed to investigate the effect of enriched 3-prebiotic formula (including inulin, fructooligosaccharides, and galactooligosaccharides) on toddler gut health by measuring fecal microbiota. Our results revealed that the consumption of 3-prebiotic formula three times per day giving total intake of 1.8 g prebiotic ingredients significantly showed the increased number of probiotic Bifidobacterium spp. colonies and the reduced populations of both C. perfringens and total anaerobic bacteria on the fecal bacterial flora in toddlers at 18~36 months. In addition, total organic acids in the fecal samples significantly increased which improves the utilization of bifidus under acidic conditions after consumption of the 3-prebiotic formula. Therefore, using the formula enriched with prebiotic may maintain gut health in toddlers. PMID:27403155

  11. A Prebiotic Formula Improves the Gastrointestinal Bacterial Flora in Toddlers.

    PubMed

    Chen, Ya-Ling; Liao, Fang-Hsuean; Lin, Shyh-Hsiang; Chien, Yi-Wen

    2016-01-01

    We aimed to investigate the effect of enriched 3-prebiotic formula (including inulin, fructooligosaccharides, and galactooligosaccharides) on toddler gut health by measuring fecal microbiota. Our results revealed that the consumption of 3-prebiotic formula three times per day giving total intake of 1.8 g prebiotic ingredients significantly showed the increased number of probiotic Bifidobacterium spp. colonies and the reduced populations of both C. perfringens and total anaerobic bacteria on the fecal bacterial flora in toddlers at 18~36 months. In addition, total organic acids in the fecal samples significantly increased which improves the utilization of bifidus under acidic conditions after consumption of the 3-prebiotic formula. Therefore, using the formula enriched with prebiotic may maintain gut health in toddlers.

  12. Variability of arsenic bioaccessibility and metabolism in soils by human gut microbiota using different in vitro methods combined with SHIME.

    PubMed

    Yin, Naiyi; Du, Huili; Zhang, Zhennan; Cai, Xiaolin; Li, Zejiao; Sun, Guoxin; Cui, Yanshan

    2016-10-01

    Arsenic (As) speciation analysis is essential when evaluating the risks upon oral exposure to As-contaminated soils. In this study, we first investigated the variability in the As bioaccessibility and speciation using a combination of five common in vitro methods (SBRC, PBET, DIN, UBM and IVG) (gastric and small intestinal phases) and the SHIME model (colon phase). Our results indicate that the As bioaccessibility varies in the colon phase. An increase in the As bioaccessibility for SBRC and PBET, and a decrease for UBM and IVG were observed in the colon phase. In addition, we found different extents of methylation and large amounts of arsenite [As(III)] due to microbial reduction in the colon digests. The UBM-SHIME method displayed a higher methylation percentage of 13.5-82.1%, but a lower methylation percentage of 0.2-21.8% was observed in the SBRC-SHIME method. Besides, The MMA(V) levels in the colon digests were positively correlated with those of As(III) and DMA(V), so DMA(V) can be considered an indicator to evaluate the As metabolic speed of in vitro cultured human gut microbiota. Based on the standard reference soil of NIST 2710a, the As bioaccessibility in the colon phase of PBET-SHIME and SBRC-SHIME were the closest to the in vivo results. Combining in vitro methods and SHIME will remarkably affect the accurate assessment of potential risks to human health associated with oral exposure to soil As. PMID:27320743

  13. Production of butyrate from lysine and the Amadori product fructoselysine by a human gut commensal.

    PubMed

    Bui, Thi Phuong Nam; Ritari, Jarmo; Boeren, Sjef; de Waard, Pieter; Plugge, Caroline M; de Vos, Willem M

    2015-12-01

    Human intestinal bacteria produce butyrate, which has signalling properties and can be used as energy source by enterocytes thus influencing colonic health. However, the pathways and the identity of bacteria involved in this process remain unclear. Here we describe the isolation from the human intestine of Intestinimonas strain AF211, a bacterium that can convert lysine stoichiometrically into butyrate and acetate when grown in a synthetic medium. Intestinimonas AF211 also converts the Amadori product fructoselysine, which is abundantly formed in heated foods via the Maillard reaction, into butyrate. The butyrogenic pathway includes a specific CoA transferase that is overproduced during growth on lysine. Bacteria related to Intestinimonas AF211 as well as the genetic coding capacity for fructoselysine conversion are abundantly present in colonic samples from some healthy human subjects. Our results indicate that protein can serve as a source of butyrate in the human colon, and its conversion by Intestinimonas AF211 and related butyrogens may protect the host from the undesired side effects of Amadori reaction products.

  14. Production of butyrate from lysine and the Amadori product fructoselysine by a human gut commensal

    PubMed Central

    Bui, Thi Phuong Nam; Ritari, Jarmo; Boeren, Sjef; de Waard, Pieter; Plugge, Caroline M.; de Vos, Willem M.

    2015-01-01

    Human intestinal bacteria produce butyrate, which has signalling properties and can be used as energy source by enterocytes thus influencing colonic health. However, the pathways and the identity of bacteria involved in this process remain unclear. Here we describe the isolation from the human intestine of Intestinimonas strain AF211, a bacterium that can convert lysine stoichiometrically into butyrate and acetate when grown in a synthetic medium. Intestinimonas AF211 also converts the Amadori product fructoselysine, which is abundantly formed in heated foods via the Maillard reaction, into butyrate. The butyrogenic pathway includes a specific CoA transferase that is overproduced during growth on lysine. Bacteria related to Intestinimonas AF211 as well as the genetic coding capacity for fructoselysine conversion are abundantly present in colonic samples from some healthy human subjects. Our results indicate that protein can serve as a source of butyrate in the human colon, and its conversion by Intestinimonas AF211 and related butyrogens may protect the host from the undesired side effects of Amadori reaction products. PMID:26620920

  15. Gut microbiota in autism and mood disorders

    PubMed Central

    Mangiola, Francesca; Ianiro, Gianluca; Franceschi, Francesco; Fagiuoli, Stefano; Gasbarrini, Giovanni; Gasbarrini, Antonio

    2016-01-01

    The hypothesis of an important role of gut microbiota in the maintenance of physiological state into the gastrointestinal (GI) system is supported by several studies that have shown a qualitative and quantitative alteration of the intestinal flora in a number of gastrointestinal and extra-gastrointestinal diseases. In the last few years, the importance of gut microbiota impairment in the etiopathogenesis of pathology such as autism, dementia and mood disorder, has been raised. The evidence of the inflammatory state alteration, highlighted in disorders such as schizophrenia, major depressive disorder and bipolar disorder, strongly recalls the microbiota alteration, highly suggesting an important role of the alteration of GI system also in neuropsychiatric disorders. Up to now, available evidences display that the impairment of gut microbiota plays a key role in the development of autism and mood disorders. The application of therapeutic modulators of gut microbiota to autism and mood disorders has been experienced only in experimental settings to date, with few but promising results. A deeper assessment of the role of gut microbiota in the development of autism spectrum disorder (ASD), as well as the advancement of the therapeutic armamentarium for the modulation of gut microbiota is warranted for a better management of ASD and mood disorders. PMID:26755882

  16. The flora of Oktibbeha County, Mississippi

    USGS Publications Warehouse

    Leidolf, A.; McDaniel, S.; Nuttle, T.

    2002-01-01

    We surveyed the flora of Oktibbeha County, Mississippi, U.S.A., from February 1994 to 1996. Occupying 118 square kilometers in east-central Mississippi, Oktibbeha County lies among 3 physiographic regions that include, from west to east, Interior Flatwoods, Pontotoc Ridge, and Black Prairie. Accordingly, the county harbors a diverse flora. Based on field work, as well as an extensive review of published literature and herbarium records at IBE and MISSA, we recorded a total of 1,148 taxa (1,125 species, 7 hybrids, 16 infraspecific taxa) belonging to 514 genera in 160 families, over 85% of all taxa documented were native. Compared to 3 other counties in east-central Mississippi, Oktibbeha County has the second largest recorded flora. The number of state-listed (endangered, threatened, or of special concern) taxa (67) documented in this survey far exceeds that reported from any other county in the region. Three introduced species, Ilex cornuta Lindl. & Paxton, Mahonia bealei (Fortune) Carrie??re, and Nandina domestica Thunb., are reported in a naturalized state for the first time from Mississippi. We also describe 16 different plant communities belonging to 5 broad habitat categories: bottomland forests, upland forests and prairies, aquatic habitats, seepage areas, and human-influenced habitats. A detailed description of the vegetation associated with each of these communities is provided.

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

    PubMed

    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

    2016-07-12

    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. Vancomycin, but not amoxicillin, decreased bacterial diversity and reduced Firmicutes involved in short-chain fatty acid and bile acid metabolism, concomitant with altered plasma and/or fecal metabolite concentrations. Adipose tissue gene expression of oxidative pathways was upregulated by antibiotics, whereas immune-related pathways were downregulated by vancomycin. Antibiotics did not affect tissue-specific insulin sensitivity, energy/substrate metabolism, postprandial hormones and metabolites, systemic inflammation, gut permeability, and adipocyte size. Importantly, energy harvest, adipocyte size, and whole-body insulin sensitivity were not altered at 8-week follow-up, despite a still considerably altered microbial composition, indicating that interference with adult microbiota by 7-day antibiotic treatment has no clinically relevant impact on metabolic health in obese humans. PMID:27411009

  18. Structural dissection of a complex Bacteroides ovatus gene locus conferring xyloglucan metabolism in the human gut.

    PubMed

    Hemsworth, Glyn R; Thompson, Andrew J; Stepper, Judith; Sobala, Łukasz F; Coyle, Travis; Larsbrink, Johan; Spadiut, Oliver; Goddard-Borger, Ethan D; Stubbs, Keith A; Brumer, Harry; Davies, Gideon J

    2016-07-01

    The human gastrointestinal tract harbours myriad bacterial species, collectively termed the microbiota, that strongly influence human health. Symbiotic members of our microbiota play a pivotal role in the digestion of complex carbohydrates that are otherwise recalcitrant to assimilation. Indeed, the intrinsic human polysaccharide-degrading enzyme repertoire is limited to various starch-based substrates; more complex polysaccharides demand microbial degradation. Select Bacteroidetes are responsible for the degradation of the ubiquitous vegetable xyloglucans (XyGs), through the concerted action of cohorts of enzymes and glycan-binding proteins encoded by specific xyloglucan utilization loci (XyGULs). Extending recent (meta)genomic, transcriptomic and biochemical analyses, significant questions remain regarding the structural biology of the molecular machinery required for XyG saccharification. Here, we reveal the three-dimensional structures of an α-xylosidase, a β-glucosidase, and two α-l-arabinofuranosidases from the Bacteroides ovatus XyGUL. Aided by bespoke ligand synthesis, our analyses highlight key adaptations in these enzymes that confer individual specificity for xyloglucan side chains and dictate concerted, stepwise disassembly of xyloglucan oligosaccharides. In harness with our recent structural characterization of the vanguard endo-xyloglucanse and cell-surface glycan-binding proteins, the present analysis provides a near-complete structural view of xyloglucan recognition and catalysis by XyGUL proteins. PMID:27466444

  19. Genome sequence of Oceanobacillus picturae strain S1, an halophilic bacterium first isolated in human gut.

    PubMed

    Lagier, Jean-Christophe; Khelaifia, Saber; Azhar, Esam Ibraheem; Croce, Olivier; Bibi, Fehmida; Jiman-Fatani, Asif Ahmad; Yasir, Muhammad; Helaby, Huda Ben; Robert, Catherine; Fournier, Pierre-Edouard; Raoult, Didier

    2015-01-01

    Oceanobacillus picturae is a strain of a moderately halophilic bacterium, first isolated from a mural painting. We demonstrate, for the first time, the culture of human Oceanobacillus picturae, strain S1(T), whose genome is described here, from a stool sample collected from a 25-year-old Saoudian healthy individual. We used a slightly modified standard culture medium adding 100 g/L of NaCl. We provide a short description of this strain including its MALDI-TOF spectrum, the main identification tool currently used in clinical microbiology. The 3,675,175 bp long genome exhibits a G + C content of 39.15 % and contains 3666 protein-coding and 157 RNA genes. The draft genome sequence of Oceanobacillus picturae has a similar size to the Oceanobacillus kimchii (respectively 3.67 Mb versus 3.83 Mb). The G + C content was higher compared with Oceanobacillus kimchii (respectively 39.15 % and 35.2 %). Oceanobacillus picturae shared almost identical number of genes (3823 genes versus 3879 genes), with a similar ratio of genes per Mb (1041 genes/Mb versus 1012 genes/Mb). The genome sequencing of Oceanobacillus picturae strain S1 isolated for the first time in a human, will be added to the 778 genome projects from the gastrointestinal tract listed by the international consortium Human Microbiome Project.

  20. Structural dissection of a complex Bacteroides ovatus gene locus conferring xyloglucan metabolism in the human gut

    PubMed Central

    Thompson, Andrew J.; Stepper, Judith; Sobala, Łukasz F.; Coyle, Travis; Larsbrink, Johan; Spadiut, Oliver; Goddard-Borger, Ethan D.; Stubbs, Keith A.; Brumer, Harry; Davies, Gideon J.

    2016-01-01

    The human gastrointestinal tract harbours myriad bacterial species, collectively termed the microbiota, that strongly influence human health. Symbiotic members of our microbiota play a pivotal role in the digestion of complex carbohydrates that are otherwise recalcitrant to assimilation. Indeed, the intrinsic human polysaccharide-degrading enzyme repertoire is limited to various starch-based substrates; more complex polysaccharides demand microbial degradation. Select Bacteroidetes are responsible for the degradation of the ubiquitous vegetable xyloglucans (XyGs), through the concerted action of cohorts of enzymes and glycan-binding proteins encoded by specific xyloglucan utilization loci (XyGULs). Extending recent (meta)genomic, transcriptomic and biochemical analyses, significant questions remain regarding the structural biology of the molecular machinery required for XyG saccharification. Here, we reveal the three-dimensional structures of an α-xylosidase, a β-glucosidase, and two α-l-arabinofuranosidases from the Bacteroides ovatus XyGUL. Aided by bespoke ligand synthesis, our analyses highlight key adaptations in these enzymes that confer individual specificity for xyloglucan side chains and dictate concerted, stepwise disassembly of xyloglucan oligosaccharides. In harness with our recent structural characterization of the vanguard endo-xyloglucanse and cell-surface glycan-binding proteins, the present analysis provides a near-complete structural view of xyloglucan recognition and catalysis by XyGUL proteins. PMID:27466444

  1. Transcarboxylase mRNA: a marker which evidences P. freudenreichii survival and metabolic activity during its transit in the human gut.

    PubMed

    Hervé, Christophe; Fondrevez, Marc; Chéron, Angélique; Barloy-Hubler, Frédérique; Jan, Gwénaël

    2007-02-15

    Dairy propionibacteria have recently been considered as probiotics which may beneficially modulate the intestinal ecosystem. However, appropriate vectors (food matrices containing the probiotic) which preserve their viability and offer good tolerance towards digestive stresses need to be developed. In addition, the development of efficient non-invasive methods which specifically monitor Propionibacterium freudenreichii concentration and activity within the human gut is required. To address this latter need, an enzyme involved in propionic fermentation, transcarboxylase, was evaluated in this study as molecular marker in P. freudenreichii. In vitro, the three transcarboxylase subunits were shown to be encoded by an operon and their expression regulated. It occurred during propionic fermentation, ceased in starved cells and was not affected by digestive stresses. The 5S subunit gene of transcarboxylase allowed specific detection of P. freudenreichii by real time PCR in the complex human faecal microbiota. A dairy vector harbouring P. freudenreichii was developed and afforded elevated probiotic faecal concentrations in humans. In vivo, this PCR method allowed rapid quantification of faecal P. freudenreichii in agreement with the cultural method (cfu counting). Moreover, real time Reverse Transcription (RT) -PCR evidenced transcription of the 5S subunit gene during transit through the human digestive tract. This work constitutes a methodological advance for survival and activity evaluation in human trials of the probiotics belonging to the P. freudenreichii species. It strongly suggests that this bacterium not only survives but remains metabolically active in the human gut. PMID:17156879

  2. Gut microbiota and metabolic syndrome.

    PubMed

    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.

  3. Gut microbiota and metabolic syndrome

    PubMed Central

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

    2014-01-01

    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. PMID:25473159

  4. Mining metagenomic whole genome sequences revealed subdominant but constant Lactobacillus population in the human gut microbiota.

    PubMed

    Rossi, Maddalena; Martínez-Martínez, Daniel; Amaretti, Alberto; Ulrici, Alessandro; Raimondi, Stefano; Moya, Andrés

    2016-06-01

    The genus Lactobacillus includes over 215 species that colonize plants, foods, sewage and the gastrointestinal tract (GIT) of humans and animals. In the GIT, Lactobacillus population can be made by true inhabitants or by bacteria occasionally ingested with fermented or spoiled foods, or with probiotics. This study longitudinally surveyed Lactobacillus species and strains in the feces of a healthy subject through whole genome sequencing (WGS) data-mining, in order to identify members of the permanent or transient populations. In three time-points (0, 670 and 700 d), 58 different species were identified, 16 of them being retrieved for the first time in human feces. L. rhamnosus, L. ruminis, L. delbrueckii, L. plantarum, L. casei and L. acidophilus were the most represented, with estimated amounts ranging between 6 and 8 Log (cells g(-1) ), while the other were detected at 4 or 5 Log (cells g(-1) ). 86 Lactobacillus strains belonging to 52 species were identified. 43 seemingly occupied the GIT as true residents, since were detected in a time span of almost 2 years in all the three samples or in 2 samples separated by 670 or 700 d. As a whole, a stable community of lactobacilli was disclosed, with wide and understudied biodiversity.

  5. Mining metagenomic whole genome sequences revealed subdominant but constant Lactobacillus population in the human gut microbiota.

    PubMed

    Rossi, Maddalena; Martínez-Martínez, Daniel; Amaretti, Alberto; Ulrici, Alessandro; Raimondi, Stefano; Moya, Andrés

    2016-06-01

    The genus Lactobacillus includes over 215 species that colonize plants, foods, sewage and the gastrointestinal tract (GIT) of humans and animals. In the GIT, Lactobacillus population can be made by true inhabitants or by bacteria occasionally ingested with fermented or spoiled foods, or with probiotics. This study longitudinally surveyed Lactobacillus species and strains in the feces of a healthy subject through whole genome sequencing (WGS) data-mining, in order to identify members of the permanent or transient populations. In three time-points (0, 670 and 700 d), 58 different species were identified, 16 of them being retrieved for the first time in human feces. L. rhamnosus, L. ruminis, L. delbrueckii, L. plantarum, L. casei and L. acidophilus were the most represented, with estimated amounts ranging between 6 and 8 Log (cells g(-1) ), while the other were detected at 4 or 5 Log (cells g(-1) ). 86 Lactobacillus strains belonging to 52 species were identified. 43 seemingly occupied the GIT as true residents, since were detected in a time span of almost 2 years in all the three samples or in 2 samples separated by 670 or 700 d. As a whole, a stable community of lactobacilli was disclosed, with wide and understudied biodiversity. PMID:27043715