The Diet‐microbiota‐mucus Layer Axis as a Mediator of Intestinal Health and Disease

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Despite the accepted health benefits of consuming dietary fiber, little is known about the precise mechanisms by which fiber levels impact the gut microbiota and alters disease risk or how the precise chemistry of fiber polysaccharides interfaces with the hundreds of gut microbiota species. Using gnotobiotic mouse models, functional genomics, biochemical and genetic studies we have explored these interactions in mechanistic depth. In recent studies in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we have elucidated the functional interactions between dietary fiber, the gut microbiota and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. During chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host‐secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber‐deprived, mucus‐eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium, or inflammatory disease in the absence of pathogen in IL‐10‐deficient mice. Our work has begun to unravel the intricate pathways linking diet, the gut microbiome and intestinal barrier dysfunction, which could be exploited to improve health using dietary fiber or prebiotic therapeutics. As such, it is anticipated that our research will provide direct paths to future dietary intervention studies in humans, which are built on a firm foundation of functional and mechanistic knowledge of fiber‐microbiota interactions gathered in tractable model systems.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.