Dissecting Host-microbiome Modifiers of Type 2 Diabetes Risk

Overview

It is now well documented that changes in gut microbiota composition accompany obesity and type 2 diabetes (T2D) and contribute to low-grade inflammation, insulin resistance,and glucose intolerance. It is not yet clear if T2D predisposes the intestine to allow more microbial products or possibly live bacteria to subvert the gut mucosal barrier. However, it is known that hyperglycemia during T2D induces a more permissive gut barrier allowing increased penetration of microbes and their products into the blood. An important next step is to determine which strains of bacteria promote dysbiosis, allowing bacteria or bacterial components to subvert the gut barrier and alter glucose control. It is hypothesized that gut microbes in the colon and other lower gut segments are key modulators of energy balance, glucose homeostasis and insulin sensitivity.

The gut acts as a barrier to bacteria and nutrients and participates in glucose homeostasis via endocrine actors and the gut-brain-peripheral axis. It is unclear how T2D alters microbes in upper and lower intestine of humans. Studies in animals show that T2D promotes translocation of microbes to the blood and tissues to promote metabolic dysfunction. It is crucial to determine whether bacteria or their components subvert the gut barrier in human T2D, and then to identity the relevant bacterial strains in tissues that control blood glucose. The overall objective of our research program is to demonstrate that specific microbes in the gut, circulation, and key metabolic tissues are involved in the progression of T2D. We will define the microbial signatures of T2D in duodenal biopsies and stool samples by comparing T2D and non-T2D subjects.