Grant: CIHR Fellowship

Metabolic and gut bacterial alterations are suggested to play a role in inflammatory disorders, but the mechanisms are poorly understood. Mice whose intestine are defective in certain aspects of metabolism have dysregulated immunity. However, the pathological consequences of metabolic intestinal dysfunction and how gut bacteria play a role are not known. In this proposal, we will use mice with defective intestinal metabolism to investigate the consequences on immune function and susceptibility to inflammation. We will investigate changes in gut bacterial populations in mice with defective epithelial metabolism and use mice raised in germ-free conditions to determine the role of gut bacteria. Using an intestinal pathogen that is associated with chronic inflammatory diseases, we will determine whether epithelial metabolic dysfunction increases susceptibility to infection and inflammation. This project will allow us to determine whether metabolic disturbances in the intestine may initiate or exacerbate inflammatory responses that could contribute to chronic inflammatory diseases.