Grant: CIHR Fellowship

Diabetes is an incurable disease that affects more than 246 million people worldwide. Type 1 diabetes requires lifelong treatment (daily injections of insulin) and is associated with severe complications that frequently lead to kidney failure, blindness, heart disease and limb amputation. Thus, this disease alone has a huge impact on quality of life and health care costs. Type 1 diabetes is an autoimmune disorder in which the insulin producing beta cells in the pancreas are destroyed by one's own immune system. Through an unknown mechanism these cells, which are normally recognized as "self", are considered "foreign" by immune cells which then destroy them as though they were an invading pathogen. There is evidence that changes in the gut, induced either by diet or by microbes that reside in the gut, may alter the incidence and course of diabetes. Our hypothesis is that diabetes is accelerated/develops, in part, due to bacterial stimulation of the gut immune system. Strikingly, we find that damage to the gut by pathogenic bacteria results in a "breach" of the epithelial barrier (inner wall of the gut), and activation of immune cells that exhibit a surprising specificity for the pancreatic beta cells. A fascinating possibility is that epithelial barrier disruption by harmful gut bacteria stimulates activation of immune cells, which subsequently attack pancreatic beta cells. Concomitant with the activation of immune cells, we see a depletion of T regulatory cells, which play a critical role in suppressing inflammatory and autoimmune diseases, including Type 1 diabetes. Thus, reduction in the number of these cells may also accelerate the course of Type 1 diabetes. Our ultimate goal is to determine if activation/depletion of specific immune cells in response to pathogenic gut bacteria promotes diabetes. Learning about the interaction between gut bacteria and the onset of diabetes may allow us to prevent diabetes through the manipulation of gut microflora.