Listening to Our Gut: Contribution of Gut Microbiota and Cardiovascular Risk in Diabetes Pathogenesis

Abstract

What we understand about diabetes from decades of genetics research is now being supplemented with exciting new evidence based on a better understanding of how one of the biggest "environmental" factors the body is exposed to is influencing the pathogenesis of disease. The recent discovery that certain dietary nutrients possessing a trimethylamine (TMA) moiety (namely choline/phosphatidylcholine and L-carnitine) participate in the development of atherosclerotic heart disease has renewed attention towards the contributions of gut microbiota in the development of cardiovascular diseases. Collectively, animal and human studies reveal that conversion of these nutrient precursors to trimethylamine N-oxide (TMAO) depends on both microbial composition and host factors, and can be induced by dietary exposures. In addition, circulating TMAO levels are strongly linked to cardiovascular disease risks and various adverse cardio-renal consequences. Our group and others have further demonstrated that circulating TMAO levels are elevated in patients with type 2 diabetes mellitus compared to healthy controls and gut microbiota-dependent phosphatidylcholine metabolism has been implicated in metabolic dysregulation and insulin resistance in animal models. Therefore, preventive strategies to minimize adverse consequences associated with TMAO generation in the diabetic population are warranted.