Project 460403

Canada is a hotspot for inflammatory bowel disease (IBD): chronic conditions of the gut that affect 300,000 Canadians and are increasing in children and adults. Individuals suffering from IBD experience diarrhea, pain, weight loss, life-long medication and recurring hospitalizations, for a devastating loss of quality-of-life. The human cost of IBD is immense, impacting the patient and their family/caregiver. Currently, there is no cure for IBD, and while new drugs that suppress inflammation have brought relief to many, satisfactory medical management is not available for 40-50% of people who must live with IBD. This is not an acceptable position and there is an urgent need for new approaches to IBD. The gut is bound by a layer of cells - the epithelium - that absorbs nutrients and water, while keeping bacteria and pathogens in the lumen of the gut to limit the potential of disease. Microbes that cross this epithelial layer (i.e. a physical barrier) can promote IBD and if they enter the bloodstream, sepsis and death can ensue. Mitochondria produce energy for all the cells activities, exist in a network, and perform many roles important to normal cell function. Disruption of mitochondrial function can result in reduced epithelial barrier function. The full role of mitochondria in affecting the immune function of the epithelium and its' interaction with bacteria in the gut is poorly understood. We propose to advance knowledge of mitochondrial form and function in the epithelial cells lining the gut when they are infected with a strain of bacteria that has been implicated in the disease process of IBD. Thus, we depart from the traditional approach to study IBD that has focused on immune cells; rather, we propose research to determine if preserving mitochondrial function in gut epithelial cells can be a novel therapeutic approach to IBD.