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: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.
Project description:Gut microbiome research is rapidly moving towards the functional characterization of the microbiota by means of shotgun meta-omics. Here, we selected a cohort of healthy subjects from an indigenous and monitored Sardinian population to analyze their gut microbiota using both shotgun metagenomics and shotgun metaproteomics. We found a considerable divergence between genetic potential and functional activity of the human healthy gut microbiota, in spite of a quite comparable taxonomic structure revealed by the two approaches. Investigation of inter-individual variability of taxonomic features revealed Bacteroides and Akkermansia as remarkably conserved and variable in abundance within the population, respectively. Firmicutes-driven butyrogenesis (mainly due to Faecalibacterium spp.) was shown to be the functional activity with the higher expression rate and the lower inter-individual variability in the study cohort, highlighting the key importance of the biosynthesis of this microbial by-product for the gut homeostasis. The taxon-specific contribution to functional activities and metabolic tasks was also examined, giving insights into the peculiar role of several gut microbiota members in carbohydrate metabolism (including polysaccharide degradation, glycan transport, glycolysis and short-chain fatty acid production). In conclusion, our results provide useful indications regarding the main functions actively exerted by the gut microbiota members of a healthy human cohort, and support metaproteomics as a valuable approach to investigate the functional role of the gut microbiota in health and disease.
Project description:Omnivorous animals, including mice and humans, tend to prefer energy-dense nutrients rich in fat over plant-based diets, especially for short periods of time. The health consequences of this short-term consumption of energy-dense nutrients remain still unclear. We found that every short-term, reiterated switches to feast diets mimicking our social eating behavior, breached the potential buffering effect of the intestinal microbiota and deeply reorganized the immunological architecture of mucosa-associated lymphoid tissues. The first dietary switch was sufficient to induce transient mucosal immune depression and suppress systemic, antigen-specific immunity leading to higher susceptibility to Salmonella Typhimurium and Listeria monocytogenes infections. This was explained by a reduction of CD4+ T cell metabolic fitness and cytokine production due to impaired mTOR activity in response to withdrawal of microbial provision of fiber metabolites. Reintroducing dietary fiber efficiently rewired T cell metabolism and restored both mucosal and systemic CD4+ T cell functions and immunity. Finally, dietary intervention study in human volunteers confirmed the impact of short-term dietary switches on human CD4+ T cell functionality. This work reveals that short-term nutritional changes cause a drastic yet transient depression of both mucosal and systemic immunity, creating windows of opportunities for pathogenic infections.
Project description:Omnivorous animals, including mice and humans, tend to prefer energy-dense nutrients rich in fat over plant-based diets, especially for short periods of time. The health consequences of this short-term consumption of energy-dense nutrients remain still unclear. We found that every short-term, reiterated switches to feast diets mimicking our social eating behavior, breached the potential buffering effect of the intestinal microbiota and deeply reorganized the immunological architecture of mucosa-associated lymphoid tissues. The first dietary switch was sufficient to induce transient mucosal immune depression and suppress systemic, antigen-specific immunity leading to higher susceptibility to Salmonella Typhimurium and Listeria monocytogenes infections. This was explained by a reduction of CD4+ T cell metabolic fitness and cytokine production due to impaired mTOR activity in response to withdrawal of microbial provision of fiber metabolites. Reintroducing dietary fiber efficiently rewired T cell metabolism and restored both mucosal and systemic CD4+ T cell functions and immunity. Finally, dietary intervention study in human volunteers confirmed the impact of short-term dietary switches on human CD4+ T cell functionality. This work reveals that short-term nutritional changes cause a drastic yet transient depression of both mucosal and systemic immunity, creating windows of opportunities for pathogenic infections.