Microbial Modulation of Energy Availability in the Colon Regulates Intestinal Transit

Anita Wichmann, Ava Allahyar, Thomas U. Greiner, Hubert Plovier, Gunnel Ostergren Lunden, Thomas Larsson, Daniel J. Drucker, Nathalie M. Delzenne, Patrice D. Cani, and Fredrik Backhed.

Cell Host& Microbe. (2013) 14, 582–590.

Speaker: Chao-Hui Weng (翁肇徽)                              Time: 15:00~16:00, Sep. 24, 2014

Commentator: Dr. Ching-Hao Teng (鄧景浩老師)      Place: Room 601

Abstract:

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 can stimulate secretion of the proglucagon (Gcg)-derived incretin hormone glucagon-like peptide-1 (GLP-1), which have many effects on metabolism, including the stimulation of insulin secretion, inhibition of gastric emptying, and an increased feeling of satiety. The authors want to investigate how the gut microbiota affects the production of GLP-1 by comparing between the germ-free (GF) and conventionally raised (CONV-R) mice. They analyzed the plasma GLP-1 levels in fasting GF and CONV-R mice and found that the plasma GLP-1 levels, colonicproglucagon (Gcg) expression, and L cell number were higher in GF mice. To determine whether the energy availability in colon may affect expression in L cells they modulated energy availability in colon by manipulating the gut microbiota, and they found that after colonization, the SCFA concentration increased and Gcg mRNA expression in colon decreased in GF mice. To test whether increasing energy supply from the diet could suppress the increase in Gcg expression in GF mice, they weaned mice onto a high-fat diet (HFD) and analyzed Gcg expression in the proximal colon. As expected, the increase in colonic Gcg expression observed in GF mice in comparison with CONV-R mice on a chow diet was abolished in those fed a HFD. They further found that GF mice exhibited significantly slower small intestinal transit compared to the CONV-R controls, and blocking GLP-1 signaling with Ex-9 completely restore the transit phenotype in GF mice. In conclusion, gut microbiota regulate the basal level of GLP-1, and increasing this level may be an adaptive response to insufficient energy availability in the colon that slows intestinal transit and allows for greater nutrient absorption.

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