The convergence of carbohydrate active gene repertoires in human gut microbes.
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ABSTRACT:
SUBMITTER: Lozupone CA
PROVIDER: S-EPMC2546442 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC3511707 | biostudies-literature
Project description:Animal microbiomes play an important role in dietary adaptation, yet the extent to which microbiome changes exhibit parallel evolution is unclear. Of particular interest is an adaptation to extreme diets, such as blood, which poses special challenges in its content of proteins and lack of essential nutrients. In this study, we assessed taxonomic signatures (by 16S rRNA amplicon profiling) and potential functional signatures (inferred by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt)) of haematophagy in birds and bats. Our goal was to test three alternative hypotheses: no convergence of microbiomes, convergence in taxonomy and convergence in function. We find a statistically significant effect of haematophagy in terms of microbial taxonomic convergence across the blood-feeding bats and birds, although this effect is small compared to the differences found between haematophagous and non-haematophagous species within the two host clades. We also find some evidence of convergence at the predicted functional level, although it is possible that the lack of metagenomic data and the poor representation of microbial lineages adapted to haematophagy in genome databases limit the power of this approach. The results provide a paradigm for exploring convergent microbiome evolution replicated with independent contrasts in different host lineages. This article is part of the theme issue 'Convergent evolution in the genomics era: new insights and directions'.
| S-EPMC6560276 | biostudies-literature
Project description:MotivationCarbohydrate Active enzyme (CAZyme) families, encoded by human gut microflora, play a crucial role in breakdown of complex dietary carbohydrates into components that can be absorbed by our intestinal epithelium. Since nutritional wellbeing of an individual is dependent on the nutrient harvesting capability of the gut microbiome, it is important to understand how CAZyme repertoire in the gut is influenced by factors like age, geography and food habits.ResultsThis study reports a comprehensive in-silico analysis of CAZyme profiles in the gut microbiomes of 448 individuals belonging to different geographies, using similarity searches of the corresponding gut metagenomic contigs against the carbohydrate active enzymes database. The study identifies a core group of 89 CAZyme families that are present across 85% of the gut microbiomes. The study detects several geography/age-specific trends in gut CAZyme repertoires of the individuals. Notably, a group of CAZymes having a positive correlation with BMI has been identified. Further this group of BMI-associated CAZymes is observed to be specifically abundant in the Firmicutes phyla. One of the major findings from this study is identification of three distinct groups of individuals, referred to as 'CAZotypes', having similar CAZyme profiles. Distinct taxonomic drivers for these CAZotypes as well as the probable dietary basis for such trends have also been elucidated. The results of this study provide a global view of CAZyme profiles across individuals of various geographies and age-groups. These results reiterate the need of a more precise understanding of the role of carbohydrate active enzymes in human nutrition.
| S-EPMC4636310 | biostudies-literature
Project description:Humans have evolved intimate symbiotic relationships with a consortium of gut microbes (microbiome) and individual variations in the microbiome influence host health, may be implicated in disease etiology, and affect drug metabolism, toxicity, and efficacy. However, the molecular basis of these microbe-host interactions and the roles of individual bacterial species are obscure. We now demonstrate a"transgenomic" approach to link gut microbiome and metabolic phenotype (metabotype) variation. We have used a combination of spectroscopic, microbiomic, and multivariate statistical tools to analyze fecal and urinary samples from seven Chinese individuals (sampled twice) and to model the microbial-host metabolic connectivities. At the species level, we found structural differences in the Chinese family gut microbiomes and those reported for American volunteers, which is consistent with population microbial cometabolic differences reported in epidemiological studies. We also introduce the concept of functional metagenomics, defined as "the characterization of key functional members of the microbiome that most influence host metabolism and hence health." For example, Faecalibacterium prausnitzii population variation is associated with modulation of eight urinary metabolites of diverse structure, indicating that this species is a highly functionally active member of the microbiome, influencing numerous host pathways. Other species were identified showing different and varied metabolic interactions. Our approach for understanding the dynamic basis of host-microbiome symbiosis provides a foundation for the development of functional metagenomics as a probe of systemic effects of drugs and diet that are of relevance to personal and public health care solutions.
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Project description:Emerging studies have revealed a strong link between the gut microbiome and several human diseases. Since human gut microbiome mirrors variations in lifestyle and environment, whether associations between disease conditions and gut microbiome are consistent across populations-particularly in communities practicing traditional subsistence strategies whose microbiomes differ markedly from industrialists-remains unknown. Cardiovascular diseases are the leading cause of mortality in India affecting 55 million people, and high blood pressure is one of the primary risk factors for cardiovascular diseases. We examined associations between gut microbiome and blood pressure along with 14 other variables associated with lifestyle, dietary habits, disease conditions, and clinical blood markers in the three Assamese populations. Our analysis reveals a robust link between the gut microbiome diversity and composition and systolic blood pressure. Moreover, several genera previously associated with hypertension in non-Indian populations were also associated with systolic blood pressure in this cohort and these genera were predictors of elevated blood pressure in these populations. These findings confer opportunities to design personalized, preventative, and targeted interventions harnessing the gut microbiome to tackle the burden of cardiovascular diseases in India.
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Project description:We generated from a single blood sample five independent human mAbs that recognized the Sa antigenic site on the head of influenza hemagglutinin and exhibited inhibitory activity against a broad panel of H1N1 strains. All five Abs used the V(H)3-7 and J(H)6 gene segments, but at least four independent clones were identified by junctional analysis. High-throughput sequence analysis of circulating B cells revealed that each of the independent clones were members of complex phylogenetic lineages that had diversified widely using a pattern of progressive diversification through somatic mutation. Unexpectedly, B cells encoding multiple diverging lineages of these clones, including many containing very few mutations in the Ab genes, persisted in the circulation. Conversely, we noted frequent instances of amino acid sequence convergence in the Ag combining sites exhibited by members of independent clones, suggesting a strong selection for optimal binding sites. We suggest that maintenance in circulation of a wide diversity of somatic variants of dominant clones may facilitate recognition of drift variant virus epitopes that occur in rapidly mutating virus Ags, such as influenza hemagglutinin. In fact, these Ab clones recognize an epitope that acquired three glycosylation sites mediating escape from previously isolated human Abs.
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Project description:Human milk contains large amounts of complex oligosaccharides that putatively modulate the intestinal microbiota of breast-fed infants by acting as decoy binding sites for pathogens and as prebiotics for enrichment of beneficial bacteria. Several bifidobacterial species have been shown to grow well on human milk oligosaccharides. However, few data exist on other bacterial species. This work examined 16 bacterial strains belonging to 10 different genera for growth on human milk oligosaccharides. For this propose, a chemically defined medium, ZMB1, was used, which allows vigorous growth of a number of gut-related microorganisms in a fashion similar to complex media. Interestingly, Bifidobacterium longum subsp. infantis, Bacteroides fragilis , and Bacteroides vulgatus strains were able to metabolize milk oligosaccharides with high efficiency, whereas Enterococcus , Streptococcus , Veillonella , Eubacterium , Clostridium , and Escherichia coli strains grew less well or not at all. Mass spectrometry-based glycoprofiling of the oligosaccharide consumption behavior revealed a specific preference for fucosylated oligosaccharides by Bi. longum subsp. infantis and Ba. vulgatus. This work expands the current knowledge of human milk oligosaccharide consumption by gut microbes, revealing bacteroides as avid consumers of this substrate. These results provide insight on how human milk oligosaccharides shape the infant intestinal microbiota.
| S-EPMC2866150 | biostudies-literature
Project description:Inter-individual variability in the microbial gene complement encoding for carbohydrate-active enzymes (CAZymes) can profoundly regulate how the host interacts with diverse carbohydrate sources thereby influencing host health. CAZy-typing, characterizing the microbiota-associated CAZyme-coding genes within a host individual, can be a useful tool to predict carbohydrate pools that the host can metabolize, or identify which CAZyme families are underrepresented requiring supplementation via microbiota transplantation or probiotics. CAZy-typing, moreover, provides a novel framework to search for disease biomarkers. As a proof of concept, we used publicly available metagenomes (935) representing 310 type strain bacterial genomes to establish the link between disease status and CAZymes in the oral and gut microbial ecosystem. The abundance and distribution of 220 recovered CAZyme families in saliva and stool samples from patients with colorectal cancer, rheumatoid arthritis, and type 1 diabetes were compared with healthy subjects. Based on the multivariate discriminant analysis, the disease phenotype did not alter the CAZyme profile suggesting a functional conservation in carbohydrate metabolism in a disease state. When disease and healthy CAZyme profiles were contrasted in differential analysis, CAZyme markers that were underrepresented in type 1 diabetes (15), colorectal cancer (12), and rheumatoid arthritis (5) were identified. Of interest, are the glycosyltransferase which can catalyze the synthesis of glycoconjugates including lipopolysaccharides with the potential to trigger inflammation, a common feature in many diseases. Our analysis has also confirmed the expansive carbohydrate metabolism in the gut as evidenced by the overrepresentation of CAZyme families in the gut compared to the oral site. Nevertheless, each site exhibited specific CAZyme markers. Taken together, our analysis provides an insight into the CAZyme landscape in health and disease and has demonstrated the diversity in carbohydrate metabolism in host-microbiota which can be a sound basis for optimizing the selection of pre, pro, and syn-biotic candidate products.
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Project description: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.
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Project description:Bacterial symbionts of eukaryotes often give up generalist lifestyles to specialize to particular hosts. The eusocial honey bees and bumble bees harbor two such specialized gut symbionts, Snodgrassella alvi and Gilliamella apicola. Not only are these microorganisms specific to bees, but different strains of these bacteria tend to assort according to host species. By using in-vivo microbial transplant experiments, we show that the observed specificity is, at least in part, due to evolved physiological barriers that limit compatibility between a host and a potential gut colonizer. How and why such specialization occurs is largely unstudied for gut microbes, despite strong evidence that it is a general feature in many gut communities. Here, we discuss the potential factors that favor the evolution of host specialization, and the parallels that can be drawn with parasites and other symbiont systems. We also address the potential of the bee gut as a model for exploring gut community evolution.
| S-EPMC4615251 | biostudies-other