Grant: Operating Grant

The layer of epithelial cells that line the intestine have an important barrier function: regulating the absorption of nutrients and, at the same time, restricting the entry of potentially harmful and disease causing bacteria or other foreign matter into the body. Many disease conditions, including the inflammatory bowel diseases (IBD: incurable conditions affecting 1 in 160 Canadians) are accompanied by increased leakiness of the epithelial barrier. Indeed, descriptions of increased permeability of the gut preceding the onset of intestinal inflammation have led to the postulate that loss of epithelial barrier function can provoke intestinal disease, including IBD. We have shown that reduced energy (i.e. metabolic stress) in the epithelial cell reduces the barrier function of the epithelial cell layer. Focusing on the role that this may play in intestinal inflammation, I will use a variety of model systems to assess the mechanism(s) by which metabolic stress affects epithelial integrity and allows bacteria to cross from the lumen of the intestine into the body. The outcome of these studies will be a better understanding of the nature and regulation of intestinal permeability, and the identification of ways to control epithelial barrier function to enhance human digestive health.