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.