Project description:Within the human gut reside diverse microbes coexisting with the host in a mutually advantageous relationship. We comprehensively identified the modulatory effects of phylogenetically diverse human gut microbes on the murine intestinal transcriptome. Gene-expression profiles were generated from the whole-tissue intestinal RNA of mice colonized with various single microbial strains. The selection of microbe-specific effects, from the transcriptional response, yielded only a small number of transcripts, indicating that symbiotic microbes have only limited effects on the gut transcriptome overall. Moreover, none of these microbe-specific transcripts was uniformly induced by all microbes. Interestingly, these responsive transcripts were induced by some microbes but repressed by others, suggesting different microbes can have diametrically opposed consequences.
Project description:Gut microbes elicit specific changes in gene expression in the colon of mice. We colonized germ-free mice with microbial communities from the guts of humans, zebrafish and termites, human skin and tongue, soil and estuarine microbial mats. We used microarrays to detail the differences in global gene expression in colon tissue that are caused by the different microbial communities 28 days after gavage into the germfree animal. Three biological replicates per group, male C57BL/6 mice (12-16 weeks old)
Project description:The factors that govern the retention and abundance of specific microbial lineages within a developing intestinal microbiota remain poorly defined. Human milk oligosaccharides consumed by nursing infnats pass undigested to the distal gut where they may be consumed by microbes. We investigated the transcriptional response of Bacterides fragilis, a prominent gut resident, to the presence of HMOs.
Project description:The factors that govern the retention and abundance of specific microbial lineages within a developing intestinal microbiota remain poorly defined. Human milk oligosaccharides consumed by nursing infnats pass undigested to the distal gut where they may be consumed by microbes. We investigated the transcriptional response of Bacterides fragilis, a prominent gut resident, to the presence of HMOs. In vitro transcriptional profiles of Bacteroides fragilis obtained from biological duplicate cultures taken at middle log phase in minimal media glucose (MM-Glu) and in minimal media with human milk oligosaccharides (MM-HMO).
Project description:Gut microbes elicit specific changes in gene expression in the colon of mice. We colonized germ-free mice with microbial communities from the guts of humans, zebrafish and termites, human skin and tongue, soil and estuarine microbial mats. We used microarrays to detail the differences in global gene expression in colon tissue that are caused by the different microbial communities 28 days after gavage into the germfree animal.
Project description:<p>Findings from recent studies suggest that the community of microbes residing in the human body is important in disease etiology; however, it remains unclear whether personal factors modulate human microbial composition. Studies based on animal models indicate that differences in composition might be attributed to sex-mediated effects. We analyzed the relationship of sex, adiposity, and dietary fiber intake with gut microbial composition using fecal samples from human subjects. We explored the associations of these factors with metrics of community composition and specific taxon abundances. We found that men and women had significantly different microbial community composition and that women had reduced abundance of a major phylum. Adiposity was associated with gut microbiome composition and specifically in women but not in men. Fiber from fruits and vegetables and fiber from beans were each associated with increased abundance of specific bacterial taxa. These findings provide initial indications that sex, adiposity, and dietary fiber might play important roles in influencing the human gut microbiome. Better understanding of these factors may have significant implications for gastrointestinal health and disease prevention.</p>
Project description: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. RNA-Seq analysis of the human gut microbiome during consumption of a plant- or animal-based diet.
Project description:Genome scale metabolic model of Drosophila gut microbe Acetobacter fabarum
Abstract -
An important goal for many nutrition-based microbiome studies is to identify the metabolic function of microbes in complex microbial communities and their impact on host physiology. This research can be confounded by poorly understood effects of community composition and host diet on the metabolic traits of individual taxa. Here, we investigated these multiway interactions by constructing and analyzing metabolic models comprising every combination of five bacterial members of the Drosophila gut microbiome (from single taxa to the five-member community of Acetobacter and Lactobacillus species) under three nutrient regimes. We show that the metabolic function of Drosophila gut bacteria is dynamic, influenced by community composition, and responsive to dietary modulation. Furthermore, we show that ecological interactions such as competition and mutualism identified from the growth patterns of gut bacteria are underlain by a diversity of metabolic interactions, and show that the bacteria tend to compete for amino acids and B vitamins more frequently than for carbon sources. Our results reveal that, in addition to fermentation products such as acetate, intermediates of the tricarboxylic acid (TCA) cycle, including 2-oxoglutarate and succinate, are produced at high flux and cross-fed between bacterial taxa, suggesting important roles for TCA cycle intermediates in modulating Drosophila gut microbe interactions and the potential to influence host traits. These metabolic models provide specific predictions of the patterns of ecological and metabolic interactions among gut bacteria under different nutrient regimes, with potentially important consequences for overall community metabolic function and nutritional interactions with the host.IMPORTANCE Drosophila is an important model for microbiome research partly because of the low complexity of its mostly culturable gut microbiota. Our current understanding of how Drosophila interacts with its gut microbes and how these interactions influence host traits derives almost entirely from empirical studies that focus on individual microbial taxa or classes of metabolites. These studies have failed to capture fully the complexity of metabolic interactions that occur between host and microbe. To overcome this limitation, we reconstructed and analyzed 31 metabolic models for every combination of the five principal bacterial taxa in the gut microbiome of Drosophila This revealed that metabolic interactions between Drosophila gut bacterial taxa are highly dynamic and influenced by cooccurring bacteria and nutrient availability. Our results generate testable hypotheses about among-microbe ecological interactions in the Drosophila gut and the diversity of metabolites available to influence host traits.
Project description:Aberrant CD4+ T cell reactivity against intestinal microbes is considered to drive mucosal inflammation in inflammatory bowel diseases. The disease-relevant microbial species and the corresponding microbe-specific pathogenic T cell phenotypes remain unknown. Here, we identify common gut commensal and food-derived yeasts, as direct activators of aberrant CD4+ T cell reactions in patients with Crohn´s disease (CD). Yeast-responsive CD4+ T cells in CD display a cytotoxic Th1 phenotype and selective clonal expansion of cells highly cross-reactive to several commensal, as well as food-derived, fungal species. This indicates cross-reactive T cell selection by repeated encounter with conserved fungal antigens in the context of chronic intestinal disease. Our results highlight a role of fungi in driving immunopathology in patients with CD and suggest that both, gut-resident fungal commensals, and daily dietary intake of yeasts, may contribute to chronic activation of pathogenic CD4+ T cell responses involved in disease pathophysiology.
Project description:Intestinal microorganisms impact on health maintaining gut homeostasis and shaping the host immunity, while gut dysbiosis associates with many conditions including autism, a complex neurodevelopmental disorder with multifactorial aetiology. In autism, gut dysbiosis correlates with symptom severity and is characterized by a reduced bacterial variability and a diminished beneficial commensal relationship. Microbiota can influence the expression of host microRNAs that, in turn, regulate the growth of intestinal bacteria by means of bidirectional host-gut micro-biota cross-talk. We investigated possible interactions among intestinal microbes and between them and host transcriptional modulators in autism. To this purpose, we analysed, by “omics” technologies, faecal microbiome, mycobiome and small non-coding-RNAs (particularly miRNAs and piRNAs) of children with autism and neurotypical development. Patients displayed gut dysbiosis, related to a reduction of healthy gut micro- and mycobiota, and up-regulated tran-scriptional modulators. The targets of dysregulated non-coding-RNAs are involved in intestinal permeability, inflammation and autism. Furthermore, microbial families, underrepresented in patients, participate to the production of human essential metabolites negatively influencing the health condition. Here, we propose a novel approach to analyse faeces as a whole and, for the first time, we detected miRNAs and piRNAs in faecal samples of patients with autism.