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

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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.

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Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by Basic Research and Frontier Exploration Project of Yuzhong District, Chongqing, China (No. 20190140).

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Authors

Contributions

XZ and ZHC conceived and designed the research. ZHC performed most of the experiments. JYF and SH performed parts of the experiments. YH, SYM, WJF and QY analyzed the data. ZHC and XZ wrote the manuscript. All data were generated in house. All authors agree to be held accountable for all aspects of the research and confirm that the data are accurate.

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Correspondence to Xin Zhang.

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Chen, Z., Feng, J., Hu, S. et al. Bacillus Subtilis Promotes the Release of 5-HT to Regulate Intestinal Peristalsis in STC Mice via Bile Acid and Its Receptor TGR5 Pathway. Dig Dis Sci 67, 4410–4421 (2022). https://doi.org/10.1007/s10620-021-07308-4

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  • DOI: https://doi.org/10.1007/s10620-021-07308-4

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