Fiber-deprived gut microbiota erodes the colonic mucus barrier: understanding immune dysregulation, pathogen susceptibility and prospects for improvement using prebiotics

Research question
The microbial community that lives in the human intestine plays an important role in both health and disease.Although gut bacteria supplement human nutrition by degrading dietary fiber, certain groups of these microbes have evolved the ability to alternatively degrade carbohydrates in the intestinal mucus barrier. We hypothesized that deficiency of dietary fiber leads to erosion of the protective colonic mucus barrier by commensal gut bacteria.Using a gnotobiotic mouse model, we have successfully supported our hypothesis. We saw erosion of the mucus layer as well as bacteria closely associated with the epithelial tissue, leading to the further hypotheses that a fiber-deprived gut microbiota: 1) triggers inflammatory host immune responses; and 2) renders the host more susceptible to infection by gastrointestinal pathogens.
Importance of the research question
Abnormal shifts in our gut microbial communities, vaguely know as dysbiosis, are associated with several intestinal diseases (e.g., colon cancer, inflammatory bowel disease and obesity); however, little is known about the developmental mechanisms of dysbiosis. Changed dietary lifestyles, including lower consumption of dietary fiber,are considered to be one of the drivers of dysbiosis and possibly involve alterations in the health benefits of the bacterial short-chain fatty acids (SCFAs) produced from dietary fiber. Other mechanistic aspects that link consumption of fiber to colonic health through microbiota remain to be investigated. Our study takes an innovative approach by studying mechanistic interactions among three key parameters: dietary fiber, the gut microbiota and the colonic mucus barrier. Testing our hypotheses will shed light on colonic disorders and host susceptibility to colonic pathogens, contributing substantial knowledge in the field of gastrointestinal health and disease. Moreover,our study intends to find non-invasive therapeutic dietary strategies to restore/maintain activities of fiber-degrading gut bacteria.
Objectives of the project proposal
We have developed a gnotobiotic mouse model composed of a simplified microbiota, which includes 14 sequenced species of commensal human gut bacteria. In the proposed research project, we intend to further employ our model to achieve the following objectives: 1) Investigate how a fiber-deprived gut microbiota leads to erosion of the colonic mucus layer leads and enhanced inflammatory responses and colon cancer in a dextran sodium sulfate (DSS) model. 2) Test host susceptibility to gastrointestinal pathogenesis by employing a classical rodent mucosal pathogen Citrobacter rodentium. 3) Design and test fiber-rich prebiotic diets in order to maintain activities of fiber-degrading gut bacteria and improving the thickness of colonic mucus.