The gut microbiome and metabolic syndrome

Abstract

The metabolic syndrome (MetS) is a constellation of risk factors that, if left untreated, will often progress to greater metabolic defects such as type 2 diabetes and nonalcoholic fatty liver disease. While these risk factors have been established for over 40 years, the definition of MetS warrants reconsideration in light of the substantial data that have emerged from studies of the gut microbiome. In this Review we present the existing recent literature that supports the gut microbiome's potential influence on the various risk factors of MetS. The interplay of the intestinal microbiota with host metabolism has been shown to be mediated by a myriad of factors, including a defective gut barrier, bile acid metabolism, antibiotic use, and the pleiotropic effects of microbially produced metabolites. These data show that events that start in the gut, often in response to external cues such as diet and circadian disruption, have far-reaching effects beyond the gut.

Figure 1. A model for the gut microbiome’s interaction with the intestinal epithelial barrier and its contribution to metabolic diseases.

From the top: High-fat, low-fiber diet induces intestinal dysbiosis, resulting in aberrant metabolite concentrations that disrupt GLP-2–mediated tight junction integrity. This loss of integrity makes the gut epithelium more permissive to microbial lipopolysaccharide (LPS), trimethylamine (TMA), and other metabolites entering the circulation and contributing to the chronic inflammation of liver and adipose tissue that is associated with the development of cardiovascular disease, insulin resistance, and other conditions associated with the metabolic syndrome.