Inflammatory Bowel Disease (IBD) is characterized by chronic intestinal inflammation, which causes damage to the intestinal epithelium. This inflammatory response in the small and large bowel is thought to be initiated by interactions between genes, environment, and microbes, which reside in the gastrointestinal tract. However, the mechanisms by which environmental factors modulate susceptibility to IBD remain incompletely understood.
We hypothesize that changes in the host environment alters the susceptibility of intestinal tissues to damage, which is mediated by the microbes and the host immune response against them. Our preliminary data suggest that one such environmental factor is host metabolism, which regulates the expression of tissue tolerance programs to mitigate tissue damage caused during colitis. In this proposal, we will develop a new experimental framework to study intestinal tissue tolerance and identify the underlying mechanisms by which host metabolism protects tissues from microbe- and immune-mediated damage. A better understanding of these mechanisms will provide alternative targets and strategies for therapeutic intervention in IBD.