Bacillus Subtilis Regulates Intestinal Peristalsis in Mice with Slow Transit Constipation Through the TGR5/TRPA1 Signaling Pathway

OBJECTIVE To explore the effects of Bacillus subtilis on the release of 5-HT and the TGR5/TRPA1 signaling pathway in mice with slow transit constipation(STC), so as to clarify the therapeutic effect and mechanism of Bacillus subtilis on STC. METHODS Twenty-four male C57BL/6 mice were divided into control group, model group, Bacillus subtilis group and INT-777 group. STC mouse model was established by compound diphenoxylate, and Bacillus subtilis suspension and INT-777 were gavaged after 1 h compound diphenoxylate treatment, respectively, for 14 d. The 24 h defecation volume, fecal water content and intestinal transport rate of mice were counted during the experiment. HE staining was used to observe the histological morphology and pathological degree of colon. The expression of 5-HT in colon was detected by ELISA and immunofluorescence, and the protein expressions of TGR5/TRPA1 pathway were detected by Western blotting. RESULTS It was found that compared with the control group, the 24 h defecation volume, fecal water content and intestinal transit rate in the model group were significantly decreased(P<0.01 or P<0.001), showing intestinal peristalsis disorder and pathological lesions of the colon. Bacillus subtilis and INT-777 significantly improved intestinal peristalsis and pathological damage of colon. In addition, the release of 5-HT(P<0.05 or P<0.001) and the TGR5/TRPA1 signaling pathway in the model group were inhibited, while Bacillus subtilis and INT-777 significantly increased the expression of 5-HT and activated the TGR5/TRPA1 pathway in STC mice. CONCLUSION Bacillus subtilis regulates intestinal peristalsis of STC mice by upregulating the TGR5/TRPA1 signaling pathway and promoting the release of 5-HT from enterochromaffin cells, thus playing a good role in the treatment of STC.