Background & Aims Chronic gastritis (CG) is closely associated with microecological imbalance of the "gut-gastric axis". Wenweishu Capsule (WWS) is a commonly used Chinese patent medicine for CG in clinical practice; however, its simultaneous regulatory effect and underlying mechanism on the "gut-gastric axis" have not been systematically elucidated. Methods A CG rat model was established using a composite method involving sodium deoxycholate, ammonia, ethanol, and irregular feeding. The rats were administered WWS (0.38 g·kg⁻¹·d⁻¹) via gavage for 4 weeks. The effects of WWS on gastric lesions, systemic inflammation, and gut microbiota were systematically evaluated using an integrated approach including histopathology, ELISA, 16S rRNA sequencing, PICRUSt functional prediction, and correlation analysis. Results WWS significantly improved the general condition, food intake, and body weight gain in CG rats, ameliorated pathological damage to the gastric mucosa, and reduced serum levels of TNF-α and IL-6. The mechanism may be related to the upregulation of IκBα, thereby inhibiting the NF-κB pathway and the subsequent expression of TNF-α and IL-6. More importantly, WWS effectively reversed model-induced gut microbiota dysbiosis: it restored both α- and β-diversity, increased the abundance of the anti-inflammatory bacterium Lachnospiraceae NK4A136 group, and suppressed the proliferation of potential pathogens such as Lactobacillus, Bacteroides, and Akkermansia. Functional prediction indicated that WWS upregulates beneficial functions such as carbohydrate and energy metabolism, while downregulating pathways related to bacterial infections. Correlation analysis further revealed significant associations between inflammatory factors and specific bacterial taxa (TNF-α/IL-6 showed a negative correlation with the Lachnospiraceae NK4A136 group and a positive correlation with Bacteroides). Conclusion This study systematically demonstrates that WWS employs a multi-dimensional synergistic mechanism—"suppression of the NF-κB inflammatory axis, rebalancing of the gut microbiota structure, and remodeling of microbial metabolic function"—to simultaneously ameliorate gastric pathology and microecological disorders of the "gut-gastric axis" in CG. These findings provide experimental evidence and a potential therapeutic strategy for the "microbe-drug" synergistic treatment of CG.

Chronic gastritis (CG) is linked to gut–gastric axis dysbiosis. Wenweishu Capsules (WWS) are clinically used to treat CG, but their concurrent regulatory effects on this axis remain unclear. A CG rat model was established using sodium deoxycholate, ammonia, ethanol, and irregular feeding. Rats received WWS (0.38 g·kg⁻¹·d⁻¹) for 4 weeks. Gastric lesions, inflammation, and gut microbiota were evaluated via histopathology, ELISA, 16S rRNA sequencing, PICRUSt prediction, and correlation analysis. WWS improved general condition, food intake, and weight gain in CG rats, alleviated gastric mucosal damage, and reduced serum TNF-α and IL-6. These effects were associated with altered IκBα expression and NF-κB pathway modulation. WWS reversed gut microbiota dysbiosis, restored α- and β-diversity, increased Lachnospiraceae NK4A136 group abundance, and suppressed potential pathogens. Functional prediction showed that WWS upregulated beneficial pathways such as carbohydrate metabolism and downregulated infection-related pathways. Correlation analysis linked TNF-α/IL-6 negatively with the Lachnospiraceae NK4A136 group and positively with Bacteroides. WWS ameliorates CG through a multi-dimensional mechanism that may involve modulation of the NF-κB inflammatory axis, rebalancing of gut microbiota structure, and remodeling of microbial metabolic function. These findings provide preliminary evidence for a potential microbe–drug interaction strategy for CG, though causal relationships require further mechanistic validation.