Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Inflammatory bowel disease (IBD), including ulcerative colitis (UC), is a debilitating disease characterized by chronic inflammation caused by multiple factors involving the immune system and the intestinal microbiota. It is a disease that is increasing in prevalence worldwide and currently affecting over 200,000 Canadian children, women and men. Recently, the millions of commensal bacteria mammals harbour, termed the microbiota, have been implicated as an initiating factor of this disease. The microbiota is essential for nutrient acquisition, metabolism of indigestible compounds, defense against colonization by pathogens, and the function of the immune system. Patients suffering from UC exhibit significant differences in composition of the intestinal microbiota compared to healthy individuals but it is unknown if this difference precedes and contributes to the onset of UC or if it is a result of UC. During the disease stage of UC, immune defenses break down, such as the intestinal mucus layer. In my research, I aim to characterize how antibiotic administration changes the composition of the intestinal microbiota and determine if these changes are sufficient to alter immune defenses in the intestine. The intestinal mucus is a critical defense barrier between microbes and host, preventing constant inflammation in response to the microbiota. Our hypothesis is that by changing the composition of the microbiota, using antibiotics, this defense will break down and subsequently increase susceptibility to colitis. The model system I will use involves utilizing the natural mouse pathogen, Citrobacter rodentium, which results in intestinal inflammation with similar features as UC. This work will increase our understanding of the interplay between the microbiota and immune responses, and how this impacts colitis. Issues central to understanding IBD in general, and may lead to the development of new diagnostic and therapeutic tools.