Xiaoer Qixing Cha alleviates functional constipation via regulating gut microbiota and short-chain fatty acids in mice

Background: Constipation is a prevalent gastrointestinal disorder associated with gut microbiota dysbiosis. Conventional pharmacological treatments, while effective for short-term symptom relief, are limited by adverse effects, high recurrence rates after discontinuation, and risks of dependency with prolonged use. Xiaoer Qixing Cha (XQC), a well-established Chinese herbal prescription, is widely utilized in pediatric care for addressing dyspepsia, diminished appetite, and constipation. However, its therapeutic mechanisms remain poorly elucidated.

Purpose: This study was designed to comprehensively explore the therapeutic efficacy and elucidate the mechanistic basis of XQC in murine constipation models.

Study design and methods: The chemical composition of XQC was comprehensively characterized using high-resolution mass spectrometry. The therapeutic efficacy of XQC (200, 400, and 800 mg/kg) was investigated in loperamide-induced constipated mice. Changes in fecal microbiota were evaluated via 16S rRNA Sequencing. Both untargeted and targeted metabolomic analyses were carried out to explore the metabolomic profiles of mice treated with XQC. Additionally, fecal microbiota transplantation (FMT) was performed to evaluate the functional role of gut microbiota mediated by XQC in constipation.

Results: High-resolution mass spectrometry identified 141 distinct compounds in XQC. Oral administration of XQC significantly alleviated loperamide-induced constipation in mice, as evidenced by improved fecal output, increased fecal water content, enhanced intestinal motility, accelerated whole-gut transit, and modulated inflammatory cytokine levels and Mucin 2 expression. Furthermore, XQC selectively restored the gut microbiota, reversing loperamide-induced microbial dysbiosis and enriching beneficial Bacterial taxa, including norank_f__Muribaculaceae and Bacteroides. FMT experiments confirmed that the therapeutic effects of XQC were at least partially mediated by gut microbiota. Notably, XQC restored short-chain fatty acid (SCFA) levels, particularly butyrate and isobutyrate. Exogenous butyrate supplementation further alleviated constipation symptoms in mice, supporting its role in XQC's mechanism of action.

Conclusion: These findings underscore XQC's dual therapeutic role in mitigating constipation and restoring gut microbial balance, positioning it as a viable alternative to conventional therapies. Furthermore, this study establishes a theoretical foundation and clinical framework for the evidence-based application of XQC in constipation management, advancing its rational integration into pediatric and gastroenterological practice.

Butyric acid; Chinese medicine; Constipation; Gut microbiota; Xiaoer Qixing Cha.