Drug Design, Development and Therapy (Nov 2020)
The Effects of Short-Chain Fatty Acids on Rat Colonic Hypermotility Induced by Water Avoidance Stress
Abstract
FangTing Yuan,1,* Wei Tan,1,* HaiXia Ren,1 Lin Yan,1 Ying Wang,1,2 HeSheng Luo1 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China; 2Key Laboratory of Hubei Province for Digestive System Diseases, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: HeSheng Luo Email [email protected]: Short-chain fatty acids (SCFAs) have been reported to play an important role in regulating gastrointestinal motility. The aim of this study is to investigate the possible role of SCFAs in water avoidance stress-induced colonic hypermotility.Methods: A rat IBS model was established by water avoidance stress (WAS). Intestinal motility was assessed by fecal pellets expulsion. The fecal SCFA level was detected using gas chromatography-mass spectrometry (GC-MS). Western blotting was performed to assess the expression of SCFAs receptors. To determine the role of SCFAs in gut dysmotility, the rats of the WAS+SCFAS and SCFAs group were administrated with oral SCFAs. The colonic contractile activity was recorded with a RM6240 multichannel physiological signal system.Key Results: WAS induced gastrointestinal hypermotility and increased defecation in rats. After repeated stress, the fecal SCFAs decreased significantly and the proportion of acetic acid, propionic acid, and butyric acid had changed from Control 2.6:1:1.5 to WAS 2:1:2.3. Protein levels of SCFAs receptors in the colon were promoted by WAS. In addition, oral SCFAs partly inhibited the colonic spontaneous motility both for SCFAs and WAS+SCFAs group in vivo. Meanwhile, we observed acetate had no effect on the contractile amplitudes of muscle strips, but it could slow down contractile frequency in a dose-dependent manner (1– 100 mM). Propionate significantly inhibited the motor activity of colonic strips (1– 30 mM). Butyrate inhibited the contractile amplitude of CM strips in a dose-dependent manner (1– 30 mM), but for LM, it exhibited a stimulating effect at low concentrations of butyrate 1 mM– 10 mM and was suppressed at high concentrations of 30 mM butyrate. Total SCFAs increased the contractile amplitude at low concentration (5– 50 mM) and inhibited it at high concentration (50– 150 mM). All SCFAs slowed down the frequency of colonic activity.Conclusion: The stress-induced colonic hypermotility by WAS could be ameliorated through oral SCFA supplementation. SCFAs may have potential clinical therapeutic use in modulating gut motility.Keywords: gastrointestinal motility, SCFAs, chronic stress, IBS
