Chaihuang weikuining protects against ethanol-induced gastric ulcer through modulation of gut microbiota and inhibition of JAK1/STAT3 signaling

Background Chaihuang weikuining (CHWKN) is a traditional Chinese medicinal formula with reported anti-ulcer activity. However, the underlying mechanisms remain unclear. This study aimed to investigate the protective effects of CHWKN against ethanol-induced gastric ulcer (GU) and to explore the role of gut microbiota in mediating these effects. Methods An ethanol-induced GU model was established in rats. Histological staining (H&E and PAS) and biochemical analyses were used to evaluate gastric injury. Antibiotic (ABX) treatment and fecal microbiota transplantation (FMT) were performed to determine the involvement of gut microbiota. 16S rDNA sequencing was conducted to analyse microbial composition. Results CHWKN markedly alleviated ethanol-induced gastric mucosal injury, as evidenced by improved histopathological features and restored of gastric function. CHWKN significantly reduced myeloperoxidase (MPO) and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and LPS) while increasing IL-10 levels, accompanied by suppression of JAK1/STAT3 signaling. Notably, depletion of gut microbiota abolished the protective and anti-inflammatory effects of CHWKN. Conversely, FMT from CHWKN-treated donors (the donor rats treated with ethanol and CHWKN) restored gastric mucosal integrity and reduced inflammation in recipient rats. Furthermore, CHWKN remodeled the composition of gut microbiota by increasing potentially beneficial bacteria and reversing ethanol-induced dysbiosis. Conclusion These findings demonstrate that CHWKN exerts protective effects against ethanol-induced GU by modulating of gut microbiota and subsequently inhibiting of JAK1/STAT3 -mediated inflammation. This highlights a microbiota-dependent mechanism underlying its therapeutic action.