Gegen Qinlian decoction alleviates DSS-induced colitis in mice through coordinated modulation of gut microbiota, serum metabolome, and colonic γδT cell responses

Background Ulcerative colitis (UC) is a chronic, relapsing inflammatory bowel disease. Despite advances in current therapies, safer, more effective drugs are urgently needed. Traditional Chinese herbal formula Gegen Qinlian Decoction (GQD) has been used for gastrointestinal disorders, including UC, though its exact mechanisms require further clarification. Objective This study aimed to systematically evaluate the therapeutic effects of GQD in UC mice, focusing on serum metabolomics, gut microbiota, and immunomodulatory mechanisms. Methods A dextran sulfate sodium (DSS)-induced mouse model of UC was established. Serum metabolomics and 16S rRNA sequencing analysis of GQD’s effects on metabolites and gut microbiota. Correlation analysis and network pharmacology identified potential targets and pathways of GQD. Immunofluorescence detected the expression of γδT cells, TNF-α, IFN-γ, and IL-17 proteins in the colonic tissue. Results Using UPLC-QE-Orbitrap-MS, 71 compounds were identified in the GQD quality control analysis. GQD markedly attenuated colonic histopathological damage and suppressed serum pro-inflammatory cytokines IFN-γ, IL-17, and TNF-α. It also modulated key serum metabolites, including succinic acid, glyoxylate, and xanthine, which are primarily involved in amino acid and purine metabolic pathways. GQD further influenced intestinal microbial diversity and composition. Joint analysis revealed GQD modulates gut microbiota, serum amino acid and purine metabolism, and inflammation pathways. Immunohistochemical results demonstrated enhanced infiltration of γδT cells following GQD treatment, accompanied by reduced protein expression levels of TNF-α, IFN-γ, and IL-17. Conclusion GQD exerts therapeutic effects on UC by reshaping gut microbiota composition and metabolic activities, thereby ameliorating intestinal mucosal injury, regulating γδT cell-mediated immune responses, and influencing amino acid and purine metabolic pathways.