Qingtong treatment principle alleviates opioid-induced constipation by regulating bile acid homeostasis via an FXR-dependent manner.

ETHNOPHARMACOLOGICAL RELEVANCE: Opioid-induced constipation (OIC) is a common and significant side effect in cancer patients receiving long-term opioid therapy. Qingtong Tea Bags (QTB), based on Qingtong Therapy principles, are widely used in the clinical treatment of OIC, but their specific molecular mechanisms remain unclear.

AIM OF THE STUDY: This study investigated whether QTB alleviate OIC by modulating gut microbiota and bile acid homeostasis.

MATERIALS AND

METHODS

We established an OIC model in C57BL/6 mice. Mice were divided into six groups: control, model, low-dose QTB, medium-dose QTB, high-dose QTB, and lactulose. We assessed fecal characteristics, gastrointestinal motility, serum inflammatory factors, intestinal barrier function, gut microbiota, and bile acid homeostasis-related gene expression. We also used Fxr-/- mice to investigate FXR's role.

RESULTS

QTB treatment significantly increased fecal water content and enhanced gastrointestinal motility, improving gastric emptying and intestinal propulsion. QTB reduced serum inflammatory markers (TNF-α, IL-1β, IL-6) and restored intestinal barrier function by upregulating Occludin, Claudin-1, and ZO-1. Using 16S rRNA sequencing, QTB was shown to significantly alter gut microbiota composition in OIC mice, indicating microbial balance restoration. Untargeted metabolomics identified seven potential biomarkers enriched in 28 KEGG pathways. QTB modulated bile acid homeostasis by regulating FXR, BSEP, and SHP expression. The pivotal role of FXR was confirmed, as QTB's effects diminished in Fxr-/- mice.

CONCLUSION

QTB alleviates OIC by modulating gut microbiota and bile acid homeostasis, with FXR acting as a key mediator. These findings highlight QTB's therapeutic potential for managing OIC and warrant further clinical investigation.