Role of Diabetes Associated Intestinal Dysbiosis in cardiac disease

Project Summary/ Abstract: Gut microbiota dysbiosis is associated with many chronic inflammatory diseases. Accordingly, previous studies have shown intestinal microbiota dysbiosis correlates increased risk of cardiac disease (CD) in diabetic patients. Yet, the role of diabetes induced alteration of gut microbiota in CD remains largely unexplored. Recent work from our lab showed that transplant of microbiotas from diabetic mice to non- diabetic mice did not impact glycemic control but rather conferred marked cardiac dysfunction in recipient mice, thus providing initial evidence that diabetic-mediated changes in the intestinal microbiota may impact heart function, irrespective of dysglycemia. Our central hypothesis is that diabetes-induced gut microbiota dysbiosis, leads to increased gut permeability and translocation of bacteria and their products in a manner that contributes to inflammation and heart dysfunction. Thus, manipulating microbiota may provide a means to prevent CD in diabetic mellitus. The initial aim of this proposal is to characterize microbial targets that lead to inflammation and CD. The second specific aim is to examine the extent to which diabetes-induced alterations in microbiota result in dissemination of gut bacteria or their products leads to impaired heart function. Aim2 will also investigate role of reduced gut motility and elevated intestinal luminal glucose levels in driving microbiota dysbiosis. Finally, we will explore potential approaches to target gut microbiota or gut barrier function therapeutically thus lowering risk of CD in person with diabetes mellitus. We will use a variety of immunological, microbiological, nanotechnological techniques in the proposed project. We anticipate discovery of novel mechanism by which gut microbiota links diabetes and CD. Furthermore, we expect to develop therapeutic strategies to maintain a healthy intestinal-microbiota relationship that will avoid bacteria translocation and inflammation that leads to impaired heart function in diabetes mellitus.