Microbial Modulation of Energy Availability in the Colon Regulates Intestinal Transit

Gut microbiota contribute to host metabolic efficiency by increasing energy availability through the fermentation of dietary fiber and production of short-chain fatty acids (SCFAs) in the colon. SCFAs are proposed to stimulate secretion of the proglucagon (Gcg)-derived incretin hormone GLP-1, which stimulates insulin secretion (incretin response) and inhibits gastric emptying. We find that germ-free (GF) and antibiotic-treated mice, which have severely reduced SCFA levels, have increased basal GLP-1 levels in the plasma and increased Gcg expression in the colon. Increasing energy supply, either through colonization with polysaccharide-fermenting bacteria or through diet, suppressed colonic Gcg expression in GF mice. Increased GLP-1 levels in GF mice did not improve the incretin response but instead slowed intestinal transit. Thus, microbiota regulate the basal levels of GLP-1, and increasing these levels may be an adaptive response to insufficient energy availability in the colon that slows intestinal transit and allows for greater nutrient absorption. •Basal levels of the incretin hormone GLP-1 are elevated in mice lacking gut microbiota•Elevated GLP-1 is due to increased proglucagon (Gcg) expression in the colon•Intestinal colonization increases SCFAs and energy availability, which suppresses Gcg•Increased GLP-1 in germ-free mice results in slower intestinal transit