Grant: Project Grant

Ulcerative colitis (UC) is a complex disease for which there is unfortunately still no cure. Current treatment approaches mainly focus on controlling the patient's immune response. However, this type of approach is ineffective for many patients. We identified a protective factor for prevention of colon inflammation. This new factor is called the Shp-2 protein. In a mouse animal model of disease, mice that are deficient for this protective Shp-2 factor in their intestinal lining exhibit increased mucosal permeability to luminal antigens and develop severe colitis. Interestingly, we found that certain tell-tale changes occurred in the gut bacteria of these mice before the disease. Indeed, we observed certain bacteria called "Enterobacteriaceae" in abnormally high levels, whereas others called "Firmicutes" in abnormally low levels in the gut of these mice. Such changes in the gut microbiota composition is also called "dysbiosis". This phenomenon occurs before the appearance of colitis and we found that antibiotic treatment successfully delayed colitis and reduced its severity. Does dysbiosis cause colonic barrier dysfunction and inflammation in our Shp-2 deficient mice model? If so, how? Could it be that our critical protective factor Shp-2 is modulating colon sensitivity to bacterial by-products? Our plan is to try killing off Enterobacteriaceae to prevent and treat dysbiosis in Shp-2 deficient mice. To do so, instead of using broad-spectrum antibiotics, we will reshape the gut microbiota and home-in on Enterobacteriaceae using a special probiotic tool. This exciting project focuses on new angles and perspectives to developing useful treatment options for UC in the future.