Dietary fiber-deprived gut microbiota in Inflammatory Bowel Disease (IBD)

Inflammatory Bowel Disease (IBD) – a chronic condition involving ulcerative colitis and Crohn’s disease – is steadily increasing in the worldwide population. As a chronic disease, IBD not only drastically affects the quality of life, but also increases mortality due to other associated complications such as cancer. The treatment of IBD continues to be a challenge and the pathogenesis mechanisms are poorly understood, although several genetic and environmental factors are linked to the disease. Recently, one of the major contributors of IBD is thought to be the gut microbiome – since dietary fibers drive the metabolism of the microbiome, deficiency of dietary fiber has been proposed as one of the potential factors behind the pathogenesis of IBD. Moreover, IBD patients often show an altered or reduced colonic mucus layer, which is the host’s first line of defense against pathogenic and commensal microbes. However, little is known about how the mechanistic interactions between dietary fiber, the gut microbiome and the colonic mucus layer contribute to the pathogenesis of IBD. Using a gnotobiotic mouse model containing a human gut microbiota, the host laboratory to this research proposal has recently shown that a dietary fiber-deprived gut microbiome erodes the colonic mucus barrier and enhances susceptibility to enteric pathogens (Desaiet al., 2016, Cell, 167, 1339). In the proposed PhD project, we further hypothesize that an IBD-associated gut microbiome is unbalanced towards degradation of the host-secreted colonic mucus. We seek to test this hypothesis by transplanting the gut microbiota from IBD patients into germ-free mice,and by following the dynamics of the microbiota-mediated colonic mucus degradation during feeding of diets rich and deficient in fiber. These experiments will shed important light on understanding the role of diet in the pathogenesis of IBD, and may help to design dietary therapeutic strategies to combat IBD.