Unravelling specific diet and gut microbial contributions to inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic condition characterized by periods of spontaneous intestinal inflammation and is increasing in industrialized populations. Combined with host genetic predisposition, both diet and gut bacteria are thought to be prominent environmental features contributing to IBD, but little is known about the precise mechanisms. We show that low dietary fiber promotes bacterial erosion of the protective colonic mucus layer, leading to lethal colitis in interleukin-10-deficient mice. This diet-induced inflammation is specifically driven by mucin-degrading bacteria-mediated Th1 immune responses and is preceded by expansion of natural killer T cells and reduced immunoglobulin A coating of specific bacterial species. Low fiber, exclusive enteral nutrition reduced disease in part by increasing bacterial production of the metabolite isobutyrate, which was dependent on the presence of soy protein in the diet. Our results highlight a mechanistic framework to unravel the complex web of potentially opposing diet, host and microbial factors that combine to influence IBD development.