Run Chang Tong Mi tea alleviates functional constipation through regulating gut microbiota and SCF/c-kit pathway.

BACKGROUND

Functional constipation (FC) is a gastrointestinal motility disorder related to intestinal transit function and hormonal imbalance and has been reported to be associated with an imbalance in the gut microbiota. Clinically, Run Chang Tong Mi tea (RCTM) can effectively alleviate the constipation symptoms of patients with FC. However, the mechanism by which RCTM improves FC and its regulation of intestinal homeostasis remain unclear.

PURPOSE: This study aims to investigate the potential mechanism of RCTM alleviates FC by improving intestinal motility and mucosal secretion function through gut microbiota and its metabolites.

METHOD: The FC rat model was established by loperamide hydrochloride. The treatment effect of RCTM was evaluated by assessing stool frequency, fecal water content, time to first black stool, and small bowel transit rate. The histological changes of colon were observed by HE staining. Serum and colonic hormone levels were measured by ELISA. Immunohistochemistry was performed to assess the expression of tight junction proteins associated with the intestinal barrier. Western blotting and RT-qPCR were used to analyze the expression of SCF/c-kit pathway and intestinal barrier related proteins and mRNA, 16S rDNA sequencing was used to analyze the composition of intestinal microbiota, and GC/MS was used to detect SCFAs levels. By transplanting RCTM-treated fecal bacteria into FC rats, the relationship between the disturbance of gut microbiota, the onset of FC and the effect of RCTM intervention was further clarified.

RESULTS

RCTM can effectively restore the gastrointestinal motility and repair the damaged intestinal barrier in FC rats. RCTM promoted the secretion of excitatory hormones and neurotransmitters in the gastrointestinal tract, and regulated the mRNA and protein content of SCF/c-kit pathway. Furthermore, RCTM restored gut microbiota disorder and SCFAs content. More importantly, RCTM-FMT effectively alleviated constipation symptoms and increased gastrointestinal hormone and neurotransmitter levels, effects that were associated with alterations in the abundance of Lachnospiraceae and Lactobacillus as well as enhanced SCFA production. Moreover, RCTM-FMT improved intestinal barrier function, which was associated with decreased abundances of Escherichia-Shigella and Dubosiella.

CONCLUSION

Our findings indicate that RCTM alleviated constipation in rats with FC, and this amelioration was associated with modulation of the gut microbiota, elevation of SCFAs, and restoration of the SCF/c-kit pathway.