Microbially induced expression of GLP-1 can regulate intestinal transit

▸ Plovier H, Lunden GO, Larsson T, et al. Microbial modulation of energy availability in the colon regulates intestinal transit. Cell Host Microbe 2013;14:582–90.

The gut microbiota has coevolved with the host and contributes to host metabolic efficiency through fermentation of dietary substrates and the production of short-chain fatty acids (SCFAs) such as butyrate, acetate and lactate. In humans consuming a Western diet microbially produced SCFAs contribute to approximately 10% of total energy requirements and is much higher than this for people consuming high-fibre diets. SCFAs, act as a primary energy source for colonocytes. They are also proposed to stimulate secretion of the proglucagon (Gcg)-derived incretin hormone GLP-1, which stimulates insulin secretion and inhibits gastric emptying. Wichmann and colleagues investigated how the gut microbiota affected GLP-1 production by comparing germ-free and conventionally raised mice. They showed that in the absence of microbially produced SCFAs there was increased plasma GLP-1, and this GLP-1 derived from the colon had an important role in slowing small bowel transit. Increasing energy availability by re-introducing short-chain or long-chain fatty acids (either through microbial colonisation or dietary fatty acid supplementation) led to reduced colonic Gcg expression. This suggests that there is a local sensing of energy availability that regulates basal GLP-1 secretion according to need. Antibiotic treatment of conventionally raised mice also resulted in reduced SCFA levels and increased Gcg expression and GLP-1 levels. The authors suggest that continuous production of SCFAs by the gut microbiota under normal physiological conditions may play a role in establishing basal GLP-1 levels. They propose that colonic GLP-1 has an important role in slowing intestinal transit in response to insufficient energy availability in the colon. The findings eloquently demonstrate a further example of how the gut microbiota contributes to host physiology and potentially holds the key …