Dietary fiber-deprived gut microbiota degrades the protective mucus barrier and promotes pathogen susceptibility. mouse gut metagenome

Little is known about how chronic or periodic dietary fiber deprivation impacts metabolism of the human gut microbiota and potentially leads to deterioration of colonic health. Here, we elucidated the mechanistic interactions among dietary fiber, the gut microbiota and the protective colonic mucus barrier that is one of the host’s first lines of defence. We employed a tractable approach consisting of a synthetic community of fully sequenced human gut bacteria assembled in gnotobiotic mice. The members of this community were selected to represent the phylogenetic diversity in a complete microbiota, but also based on empirical knowledge of their abilities to degrade various fiber polysaccharides and mucin glycans in vitro. The responses of this synthetic microbiota, and the corresponding impact on the host colonic mucus layer, to variation of dietary fiber were monitored by multiple readouts in conditions where mice were fed constant high- or low-fiber diets or daily alternations of the two. We show that starvation of dietary fiber diminishes the colonic mucus barrier by enhancing the activities of mucin-degrading bacteria. One-day alternations of the fiber-rich and fiber-free diets or feeding of a “prebiotic” diet still displayed thinner mucus barriers reflecting a residual increase in mucus-degrading bacteria and their mucin glycan-degrading enzymes. The microbiota starved of dietary fiber led to low-grade intestinal inflammation and heightened susceptibility to infection by a mucosal pathogen, Citrobacter rodentium, illustrating adverse effects of diet lacking complex natural fiber.