Grant: CIHR Fellowship

Canada has one of the highest rates of Crohn's disease (CD) in the world. This chronic inflammatory disorder of the gastrointestinal tract significantly reduces the quality of life for the 130 000 Canadians living with CD as they experience symptoms of abdominal pain, diarrhea, nausea, and fatigue. While the composition of bacteria in the gut is severely altered in CD patients, it is unclear whether this is secondary to intestinal inflammation or plays a causal role in the disease. Moreover, it is unclear whether a specific bacterium can trigger disease in genetically susceptible individuals. A major limitation in understanding the causes of CD is the lack of experimental models that address these factors. Intriguingly, we found that the deficiency of genes involved in bacteria detection and killing triggers spontaneous intestinal inflammation in mice that resembles CD pathology. Furthermore, development of disease in the genetically susceptible host required the presence of Mucispirillum schaedleri (Mucispirillum), a bacterium that inhabits the colon of normal mice. The current proposal focuses on identifying the processes by which bacteria sensing and Mucispirillum accumulation causes CD-like pathology. This work provides important insights into the causes of CD and offers the possibility of targeting specific-disease causing bacterium as an innovative strategy to treat the CD.