Role of Diabetes Associated Intestinal Dysbiosis in cardiac disease

项目摘要/摘要： 肠道微生物区系失调与许多慢性炎症性疾病有关。相应地，以前的 研究表明，肠道微生物区系失调与心脏病(CD)风险增加相关 糖尿病患者。然而，糖尿病引起的肠道微生物区系改变在CD中的作用仍然很大 未被开发的。我们实验室最近的工作表明，将糖尿病小鼠的微生物移植到非糖尿病小鼠体内 糖尿病小鼠不影响血糖控制，而是导致明显的心功能障碍 受体小鼠，从而提供了糖尿病介导的肠道微生物区系变化的初步证据 可能会影响心脏功能，与血糖异常无关。我们的中心假设是糖尿病引起的 肠道微生物区系失调，导致肠道通透性增加和细菌及其 导致炎症和心脏功能障碍的产品。因此，操纵 微生物区系可能为预防糖尿病中的镉提供了一种手段。这项建议的最初目的是 确定导致炎症和CD的微生物靶标的特征。第二个具体目标是检查 糖尿病引起的微生物区系改变导致肠道细菌或 他们的产品会导致心脏功能受损。AIM2还将研究肠道动力减弱的作用 以及促进微生物区系失调的肠腔葡萄糖水平升高。最后，我们将探索 以肠道微生物区系或肠道屏障功能为靶点从而降低风险的潜在方法 糖尿病患者体内Cd的含量。我们将使用各种免疫学、微生物学、 在拟议的项目中使用纳米技术。我们期待通过以下方式发现新的机制 哪个肠道微生物区系将糖尿病和CD联系在一起。此外，我们希望开发治疗策略 保持健康的肠道-微生物区系关系，避免细菌易位和 导致糖尿病患者心脏功能受损的炎症。

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.