Metabolites Linking the Gut Microbiome with Risk for Type 2 Diabetes

Abstract

Purpose of review: An increasing body of evidence suggests that the gut microbiome influences the pathogenesis of insulin resistance and type 2 diabetes (T2D). In this review, we will discuss the latest findings regarding the mechanisms linking the gut microbiome and microbial metabolites with T2D and therapeutic approaches based on the gut microbiota for the prevention and treatment of T2D.

Recent findings: Alterations in the gut microbial composition are associated with the risk of T2D. The gut microbiota can metabolize dietary- and host-derived factors to produce numerous microbial metabolites, which are involved in metabolic processes modulating nutrition and energy harvest, gut barrier function, systemic inflammation, and glucose metabolism. Microbial metabolites are important mediators of microbial-host crosstalk impacting host glucose metabolism. Furthermore, microbiome-based interventions may have beneficial effects on glycemic control. Future research is required to develop personalized T2D therapy based on microbial composition and/or metabolites.

Keywords: Branched-chain amino acids; Gut microbiome; Insulin resistance; Microbial metabolites; Short-chain fatty acids; T2D.

Figure 1.

Metabolites linking the gut microbiota and T2D. SCFAs regulate host glucose homeostasis in part by stimulating the secretion of PYY and GLP-1 through binding to the receptors on intestinal epithelial cells. Indole derivatives have beneficial effects on insulin sensitivity. Bile acids may promote GLP-1 secretion and improve insulin sensitivity. BCAA, TMAO and ImP impair host glucose metabolism. In addition, increased gut permeability facilitates endotoxemia, whereby LPS released by the death of gram-negative bacteria crosses the epithelial barrier and enters the circulation, inducing inflammation, which impairs insulin sensitivity. SCFA, short-chain fatty acid; PYY, peptide YY; GLP-1, glucagon-like peptide-1; BCAA, branched-chain amino acid; TMAO, trimethylamine-N-oxide; ImP, imidazole propionate; LPS, lipopolysaccharide.