ABSTRACT: Despite accepted health benefits of dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic model, in which mice were colonized with a synthetic human gut microbiota, we elucidated the functional interactions between dietary fiber, the gut microbiota and the colonic mucus barrier, which serves as a primary defence against pathogens. We show that 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 promoted greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium, but only in the presence of a fiber-deprived microbiota that is pushed to degrade the mucus layer. Our work reveals intricate pathways linking diet, gut microbiome and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics. Germ-free mice (Swiss Webster) were colonized with synthetic human gut microbiota comprising of 14 species belonging to five different phyla (names of bacterial species: Bacteroides thetaiotaomicron, Bacteroides ovatus, Bacteroides caccae, Bacteroides uniformis, Barnesiella intestinihominis, Eubacterium rectale, Marvinbryantia formatexigens, Collinsella aerofaciens, Escherichia coli HS, Clostridium symbiosum, Desulfovibrio piger, Akkermansia muciniphila, Faecalibacterium prausnitzii and Roseburia intestinalis). These mice were fed either a fiber-rich diet or a fiber-free diet for about 6 weeks. The mice were then sacrificed and their cecal tissues were immediately flash frozen for RNA extraction. The extracted RNA was subjected to microarray analysis based on Mouse Gene ST 2.1 strips using the Affy Plus kit. Expression values for each gene were calculated using robust multi-array average (RMA) method.
