Gut microbiome and type 2 diabetes: where we are and where to go?

Type 2 diabetes mellitus (T2D) is a highly prevalent metabolic disorder characterized by an imbalance in blood glucose level, altered lipid profile and high blood pressure. Genetic constituents, high-fat and high-energy dietary habits, and a sedentary lifestyle are three major factors that contribute to high risk of T2D. Several studies have reported gut microbiome dysbiosis as a factor in rapid progression of insulin resistance in T2D that accounts for about 90% of all diabetes cases worldwide. The gut microbiome dysbiosis may reshape intestinal barrier functions and host metabolic and signaling pathways, which are directly or indirectly related to the insulin resistance in T2D. Thousands of the metabolites derived from microbes interact with the epithelial, hepatic and cardiac cell receptors that modulate host physiology. Xenobiotics including dietary components, antibiotics and nonsteroidal anti-inflammatory drugs strongly affect the gut microbial composition and can promote dysbiosis. Any change in the gut microbiota can shift the host metabolism towards increased energy harvest during diabetes and obesity. However, the exact mechanisms behind the dynamics of gut microbes and their impact on host metabolism at the molecular level are yet to be deciphered. We reviewed the published literature for better understanding of the dynamics of gut microbiota, factors that potentially induce gut microbiome dysbiosis and their relation to the progression of T2D. Special emphasis was also given to understand the gut microbiome induced breaching of intestinal barriers and/or tight junctions and their relation to insulin resistance.