Project description:β-Mannans are plant cell wall polysaccharides that are commonly found in human diets. However, a mechanistic understanding into the key populations that degrade this glycan is absent, especially for the dominant Firmicutes phylum. Here, we show that the prominent butyrate-producing Firmicute Roseburia intestinalis expresses two loci conferring metabolism of β-mannans. We combine multi-“omic” analyses and detailed biochemical studies to comprehensively characterize loci-encoded proteins that are involved in β-mannan capturing, importation, de-branching and degradation into monosaccharides. In mixed cultures, R. intestinalis shares the available β-mannan with Bacteroides ovatus, demonstrating that the apparatus allows coexistence in a competitive environment. In murine experiments, β-mannan selectively promotes beneficial gut bacteria, exemplified by increased R. intestinalis, and reduction of mucus-degraders. Our findings highlight that R. intestinalis is a primary degrader of this dietary fiber and that this metabolic capacity could be exploited to selectively promote key members of the healthy microbiota using β-mannan-based therapeutic interventions.
Project description:Background: Humans with metabolic and inflammatory diseases frequently harbor lower levels of butyrate-producing bacteria in their gut. However, it is not known whether variation in the levels of these organisms is causally linked with disease development and whether diet modifies the impact of these bacteria on health. Results: We use germ-free apolipoprotein E-deficient mice colonized with synthetic microbial communities that differ in their capacity to generate butyrate to demonstrate that Roseburia intestinalis interacts with dietary components to (i) impact gene expression in the intestine, directing metabolism away from glycolysis and toward fatty acid utilization, (ii) improve intestinal barrier function, (iii) lower systemic inflammation and (iv) ameliorate atherosclerosis. Furthermore, intestinal administration of butyrate improves gut barrier function and reduces atherosclerosis development. Conclusions: Altogether, our results illustrate how modifiable diet-by-microbiota interactions impact cardiovascular disease, and suggest that interventions aimed at increasing the representation of butyrate-producing bacteria may provide protection against atherosclerosis.
Project description:Strain Roseburia intestinalis TSDC19.2-1.1 (species Roseburia intestinalis) was isolated from the fecal microbiota of a USA female at time point zero (bacterial isolates were sequenced from this donor on day 0 and 47). The species name was assigned by genome clustering.
Project description:Insufficient dietary fiber intake is strongly associated with gut microbiome dysfunction and an increased risk of noncommunicable diseases. Synergistic synbiotics, which pair defined microbial strains with their preferred carbohydrate substrates, offer a promising strategy to restore these functions. However, the rational design of such interventions remains challenging by insufficient understanding of microbial fiber-degrading capacities and the host-relevant bioactivities of fermentation-derived metabolites. Here, we identify human colonic commensal Bacteroides intestinalis (B. intestinalis) as a key microbial mediator of dietary fiber-driven metabolic, immune, and neuronal benefits. We demonstrate that the synergistic interaction between B. intestinalis and its preferred substrate, insoluble wheat arabinoxylan abundant in dietary fiber, enhances the production of anti-inflammatory, antioxidant, and anti-diabetic phenolic compounds and bile acid species. These metabolic effects are accompanied by coordinated transcriptional remodeling in the colon and spleen that improve circadian rhythm regulation, lipid metabolism, and immune defense. Importantly, these beneficial effects are preserved in conventionally raised mice with established high fat diet-induced obesity, where BI and inWAX improves glucose tolerance along with an increased production of neuroactive compounds. Our findings uncover a mechanistic framework linking B. intestinalis-mediated fiber fermentation to gut–liver–brain crosstalk and establish a rational foundation for precision synbiotic design.