Banxia Xiexin Decoction Ameliorates Ulcerative Colitis via a Flora-Metabolite-Inflammation Axis Through Integrated Metabolomic and Microbiome Analysis.

Abstract

Banxia Xiexin Decoction (BXD), a classic traditional Chinese medicine formula traditionally used for gastrointestinal disorders, has demonstrated considerable therapeutic potential in ulcerative colitis (UC). Yet, its mechanism of action remains incompletely elucidated. In this study, we applied an integrated strategy incorporating UPLC-Q-TOF/MS-based plasma metabolomics and gut microbiome analysis to explore the anti-UC effects of BXD. In a DSS-induced murine model of UC, BXD treatment mitigated colonic inflammation, as evidenced by reduced levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), repaired intestinal barrier integrity, and restored metabolic homeostasis via regulation of tryptophan and nitrogen metabolism. Notably, BXD promoted the production of microbially derived tryptophan metabolites, including indole-3-propionic acid (IPA) and indole-3-carboxaldehyde (IAld). IAld acts as a ligand for the aryl hydrocarbon receptor (AhR), facilitating the differentiation and function of regulatory T cells (Tregs) and thereby helping to suppress excessive inflammation. Gut microbiota analysis further indicated that BXD enriched beneficial genera such as Akkermansia and Bifidobacterium, while reducing the abundance of pro-inflammatory bacteria belonging to the Lachnospiraceae family. These results demonstrate the role of BXD in modulating the flora-metabolite-inflammation axis, providing a scientific rationale for its use in UC and highlighting its multi-target actions involving anti-inflammatory effects, metabolic reprogramming, and microbiota restoration.