Banxia Xiexin Decoction modulates short-chain fatty acid metabolism and mitigates ulcerative colitis by reshaping the intestinal microbiota

Ulcerative colitis (UC) is a chronic inflammatory disorder that significantly impacts the quality of life for patients. Dysbiosis of gut microbiota and changes in short-chain fatty acid (SCFA) metabolism play a role in both the initiation and progression of UC. Banxia Xiexin Decoction (BXD), a formula in traditional Chinese medicine, has shown therapeutic effects; however, its underlying mechanism remains unclear. A rat model of colitis induced by dextran sulfate sodium (DSS) was created, and various doses of BXD were administered. The principal components of BXD were analyzed through high-pressure liquid chromatography (HPLC). In order to clarify the mechanisms, 16S rRNA sequencing, serum metabolomics, targeted profiling of SCFAs via gas chromatography-mass spectrometry (GC-MS), and assessments of enzyme activity were conducted. BXD exerted protective effects against DSS-induced UC, as indicated by attenuated histological damage and reduced expression of pro-inflammatory cytokines. Untargeted metabolomics revealed that BXD modulated multiple metabolic pathways, enhancing SCFA-related processes, such as propanoate and butanoate metabolism. GC–MS revealed that BXD could increase the level of acetate, propionate, butyrate, isobutyrate, valerate, isovalerate and hexanoate. Microbiome sequencing indicated that BXD increased the abundance of beneficial taxa (e.g. Firmicutes, Bacteroidetes), while reducing pro-inflammatory genera. Altogether, BXD restored the microbial balance and promoted anti-inflammatory metabolite production. Our results demonstrated that BXD ameliorated UC by reprogramming gut microbial composition and enhancing SCFA biosynthesis, thereby suppressing intestinal inflammation. The potential of BXD as a therapy aimed at the microbiota for UC is emphasized in these studies, which also offer mechanistic insights using multi-omics approaches.