Mechanisms Linking the Gut Microbiome and Glucose Metabolism

Abstract

This review details potential mechanisms linking gut dysbiosis to metabolic dysfunction, including lipopolysaccharide, bile acids, short chain fatty acids, gut hormones, and branched-chain amino acids.

Figure 1.

Diagram detailing the changes in gut bacterial populations, density, and metabolic activity along the gastrointestinal tract (122). The small intestine, which is the main site of nutrient absorption, contains lower populations of bacteria that are mainly aerobic and facultative anaerobes. Bile acids are predominantly reabsorbed in the ileum. The colon contains mainly anaerobic bacteria in large numbers that are able to ferment undigested fiber and metabolize remaining bile acids.

Figure 2.

Schematic of potential mechanisms linking the gut microbial community with glucose metabolism. Potential mechanisms include 1) systemic absorption of LPS, either through “leaky” tight junctions or via chylomicron uptake, with subsequent inflammation; 2) bacterial production of SCFAs with signaling effects to stimulate secretion of gut hormones GLP-1 and GLP-2 and PYY as well as nutrient effects; 3) bacterial synthesis and absorption of branched chain amino acids (AAs) that may result in insulin resistance; 4) bacterial metabolism of bile acids with local and organ-specific signaling effects, including stimulation of fibroblast growth factor-19 (FGF-19) and GLP-1. FGF-19 has metabolic effects on the FXR in the pancreatic β-cell and in the liver.