Quyushengxin formula restores the integrity of intestinal barrier by regulating the gut microbiota to ameliorate DSS-induced ulcerative colitis in mice

ETHNOPHARMACOLOGICAL RELEVANCE: The Quyushengxin formula (QYSXF), a clinically validated traditional Chinese medicine (TCM) formula, has been demonstrated to be safe and effective for the treatment of ulcerative colitis (UC), but its mechanism of action in UC treatment is still unclear. AIMS OF THE STUDY: The aim of this study was to investigate the effects of QYSXF on gut microbiota modulation in DSS-induced colitis mice and to explore its role in regulating intestinal barrier function and inflammation. MATERIALS AND METHODS: First, the chemical constituents of QYSXF and mouse plasma were identified using high-performance liquid chromatography coupled with mass spectrometry. An active UC mouse model was established by treating the mice with 3 % DSS. The efficacy of QYSXF was evaluated by colonoscopy, body weight, disease activity index (DAI), colon length and histological examinations. Faecal microbiota transplantation (FMT) was performed by transferring the faecal from QYSXF-treated donor mice to DSS-induced UC recipient mice. Intestinal barrier integrity and inflammation were assessed through immunofluorescence, ELISA, and western blotting. Additionally, 16S rDNA sequencing was used to elucidate the composition of the QYSXF-regulated microbiota. RESULTS: QYSXF effectively ameliorated local ulcer surface, reduced weight loss, decreased the DAI, restored colon length, and improved histopathological scores in UC model mice. QYSXF restored the integrity of the mechanical barrier by increasing the expression of tight junction proteins and restored the integrity of the chemical barrier through increased secretion of Mucin 2 (MUC2). FMT with faecal from QYSXF-treated mice ameliorated inflammation and restored both the mechanical barrier and the chemical barrier. Moreover, both QYSXF and FMT reduced the release of proinflammatory cytokines by inhibiting the NF-κB signalling pathway and increasing the release of anti-inflammatory cytokines. 16S rDNA sequencing demonstrated that QYSXF modulated the composition of the gut microbiota by increasing the abundance of beneficial bacterial, specifically Dubosiella and Ligilactobacillus, while concurrently reducing the prevalence of the pathogenic Escherichia-Shigella. CONCLUSIONS: The mechanism underlying the efficacy of QYSXF involves restoring the composition of the gut microbiota to improve intestinal barrier, reducing the release of proinflammatory cytokines, and ultimately alleviating UC. This research not only confirms the therapeutic potential of QYSXF in UC treatment but also, more importantly, highlights the critical role of gut microbiota regulation in restoring barrier dysfunction and mitigating inflammatory responses involved in the pathogenesis of UC.