Abstract

Background The global incidence of ulcerative colitis (UC) is increasing, yet effective clinical treatment options remain limited. Qinlian Yuyang Decoction (QYD), a modified formulation based on Gegen Qinlian Decoction (GQD), has been optimized to better alleviate the pathological characteristics of UC. Although QYD is considered potentially more suitable for UC treatment, its potential mechanism of action is still unclear. Purpose To explore the mechanism of QYD in the treatment of UC based on multi-omics. Method The therapeutic effects of QYD for UC were evaluated using the dextran sulfate sodium (DSS)-induced UC mice model. Then, 16S rRNA sequencing and untargeted metabolomics were employed to identify key microbiota and metabolites regulating the intestinal microenvironment. Furthermore, proteomic analysis was carried out to elucidate the underlying mechanisms mediated by the key metabolites. Results QYD alleviated physiochemical indices in UC mice, including weight loss, diarrhea, and bloody stools, resulting in lower Disease Activity Index (DAI) scores. It also suppressed inflammatory and intestinal barrier disruption in colonic tissues. Integrated metabolomic and 16S rRNA analyses demonstrated that the therapeutic effects of QYD on UC are mediated through enrichment of gut commensal D. longicatena and increasing tyrosine levels. Oral treatment of live D. longicatena considerably ameliorates colitis symptoms in UC mice. Tyrosine has similar protective effects against UC. Our investigation using quantitative proteomics to elucidate the mechanism of tyrosine in UC revealed that tyrosine suppresses inflammatory signaling pathways, modulates immune responses, and inhibits vascular endothelial cell migration and proliferation in the UC model—effects consistent with those of QYD. In summary, our findings indicate that QYD alleviates UC by elevating gut levels of the commensal bacterium D. longicatena and tyrosine, thereby suppressing inflammatory and immune r