BACKGROUND: Senile constipation is a common functional gastrointestinal disorder that severely affects the quality of life in elderly populations. Chronic constipation can lead to colonic dysfunction and related complications. Atractylodes macrocephala Koidz. and Raphanus sativus L. are traditional Chinese medicinal herbs known for their "Qi-replenishing and spleen-strengthening" and "digestion-promoting and stagnation-relieving" properties, respectively. The herb pair (BZLF) is effective in treating senile constipation. However, the underlying mechanisms by which BZLF alleviating senile constipation remain unclear and require further investigation.
PURPOSE: This study aims to explore how BZLF alleviates senile constipation by promoting intestinal motility via the gut microbiota-short-chain fatty acids (SCFAs)-(5-hydroxytryptamine) 5-HT axis.
METHODS: A mouse model of senile constipation was established by feeding aged mice a low-fiber diet. The therapeutic effects of BZLF were evaluated by assessing defecation frequency, fecal water content, time to first black stool, small intestine transit rate, and gastric emptying rate. Histological changes in the colon were observed using HE staining and AB-PAS staining. Immunohistochemistry and immunofluorescence were used to detect intestinal barrier-related protein expression in colonic tissues. Serum and colonic hormone levels were measured by ELISA. Western blotting and RT-qPCR were employed to analyze the expression of 5-HT signaling pathway-related proteins and mRNA. Gut microbiota composition was analyzed using 16S rDNA sequencing, and SCFAs levels were detected via GC/MS.
RESULTS: BZLF improved defecation function and promoted intestinal motility in the mouse model of senile constipation. BZLF repaired intestinal barrier damage and increased serum levels of motilin (MTL), gastrin (GAS), endothelin (ET), and acetylcholine (ACH), thereby regulating gastrointestinal hormone imbalances. BZLF modulated gut microbiota dysbiosis in senile constipated mice by significantly increasing the abundance of beneficial bacteria (Lactobacillus and Ruminococcus) and suppressing the overgrowth of harmful bacteria (Escherichia-Shigella). Additionally, BZLF elevated SCFAs levels, particularly butyrate, in feces, which activated the 5-HT signaling pathway to alleviate constipation.
CONCLUSION: BZLF significantly alleviates senile constipation. Its mechanism of action is likely related to the modulation of gut microbiota composition, promotion of SCFAs production, and subsequent activation of the 5-HT signaling pathway. This study provides strong theoretical support for the development of BZLF as a potential anti-constipation herbal medicine and offers new therapeutic strategies for the treatment of senile constipation.
