Gut Microbiota and Type 2 Diabetes Mellitus: Association, Mechanism, and Translational Applications

Abstract

Gut microbiota has attracted widespread attention due to its crucial role in disease pathophysiology, including type 2 diabetes mellitus (T2DM). Metabolites and bacterial components of gut microbiota affect the initiation and progression of T2DM by regulating inflammation, immunity, and metabolism. Short-chain fatty acids, secondary bile acid, imidazole propionate, branched-chain amino acids, and lipopolysaccharide are the main molecules related to T2DM. Many studies have investigated the role of gut microbiota in T2DM, particularly those butyrate-producing bacteria. Increasing evidence has demonstrated that fecal microbiota transplantation and probiotic capsules are useful strategies in preventing diabetes. In this review, we aim to elucidate the complex association between gut microbiota and T2DM inflammation, metabolism, and immune disorders, the underlying mechanisms, and translational applications of gut microbiota. This review will provide novel insight into developing individualized therapy for T2DM patients based on gut microbiota immunometabolism.

Figure 1

The main mechanisms between gut microbiota and T2DM. SCFAs mediate glucose homeostasis by energy supply for colonocytes, increasing intestinal hormone secretion and gluconeogenesis, decreasing gut permeability, maintaining intestinal anaerobic environment, and regulating host immune. Imidazole propionate and BCAAs can block insulin signaling and activate mTORC1 responsible for insulin resistance. Bile acids have effects on glucose metabolism by binding to FXR and TGR5 and stimulate the release of 5-hydroxy tryptamine in enterochromaffin cells to induce insulin resistance. LPS induces low-grade inflammation and insulin resistance by binding to TLR4.