Bacillus Subtilis Promotes the Release of 5-HT to Regulate Intestinal Peristalsis in STC Mice via Bile Acid and Its Receptor TGR5 Pathway

Abstract

Background Slow transit constipation (STC) is caused by intestinal peristalsis dysfunction and is closely associated with disturbance of the intestinal microecological balance. Bacillus subtilis plays a positive role in the treatment of STC, but its mechanism needs to be further explored. Aims The purpose of the present study was to explore the effects and mechanism of B. subtilis on the pathophysiology of STC. Methods A STC mouse model was established with compound diphenoxylate, following which B. subtilis was used to treat STC. The effects and possible mechanism of B. subtilis on STC were investigated by assessing intestinal motility, histology of the colon, release of 5-HT in enterochromaffin cells (ECs) and the TGR5/TRPA1 pathway. Moreover, LC-MS targeted metabolomics was used to analyze the regulation of Bacillus subtilis on bile acid metabolisms in STC mice. Results Bacillus subtilis significantly increased 24 h defecations, fecal moisture and intestinal transport rate of STC mice, improved pathological damage of the colon and showed protective effects on the intestinal tract. The release of 5-HT from ECs and the bile acid receptor TGR5/TRPA1 pathway were significantly increased in STC mice treated with B. subtilis. In addition, the metabolomics results showed that the bile acid contents of STC mice were significantly decreased, and B. subtilis could increase the bile acid composition and content of STC mice. Conclusion Bacillus subtilis regulates intestinal peristalsis of STC by promoting the release of 5-HT from ECs through bile acid metabolism and its receptor TGR5 pathway and plays a positive role in the treatment of STC.

Flavonoids in Amomum tsaoko Crevost et Lemarie Ameliorate Loperamide-Induced Constipation in Mice by Regulating Gut Microbiota and Related Metabolites

“…Bacillus coagulans was effective in alleviating the adverse effects of loperamide-induced constipation in Kunming mice [ 36 ]. B. subtilis alleviated the constipation induced by difenoxylate in STC mice [ 37 ].…”

“…In addition, 5-HT can activate the peristaltic reflex by activating 5-HT receptors at the mucosal end of intrinsic primary afferent neurons [ 52 , 53 ]. Previous studies have shown that B. subtilis could promote the release of 5-HT via bile acid and its receptor TGR5 pathway to regulate gastrointestinal motility in STC mice [ 37 ]. Bifidobacterium and Lactobacillus can promote 5-HT secretion from ECCs in constipated mice [ 54 ].…”

The Combined Use of SCD Probiotics and Tauroursodeoksikolik Asit (TUDCA) is More Effective in Controlling Anxiety-Like Behavior in Aged Rats

“…Species contained in SCD probiotics are known to have a positive effect on behavior. For example, Bacillus subtilis, one of the most well-known probiotic bacteria, produces ltryptophan, and the increase in serotonin in the hypothalamus acts as an antidepressant that reduces anxious behavior [24]. In addition, numerous animal studies indicate that Bifidobacterium longum can significantly reduce anxious behavior [25].…”

Supplementing probiotics during intermittent fasting proves more effective in restoring ileum and colon tissues in aged rats

“…The intestinal epithelium's primary food source is short-chain fatty acids (SCFAs), produced by bacterial fermentation of complex carbohydrates in the gut. [32][33][34] IF enhances the production of these SCFAs, whereas Aging is frequently correlated with escalated lipid peroxidation, culminating in oxidative damage. 14,36 This heightened oxidative stress is implicated in intensifying inflammation and fostering protein modifications, subsequently leading to the generation of reactive oxygen species and promoting lymphatic infiltration, a phenomenon that aligns with our observed results.…”

“…Our findings demonstrate that both IF and SCD Probiotics can alleviate these adverse changes associated with aging, indicating their potential as therapeutic strategies. The intestinal epithelium's primary food source is short‐chain fatty acids (SCFAs), produced by bacterial fermentation of complex carbohydrates in the gut 32–34 . IF enhances the production of these SCFAs, whereas SCD Probiotics, through constituents like Bifidobacterium bifidum and Bacillus subtilis , can increase their concentration by regulating other gut bacteria.…”