A multi-omics investigation of Zuojin Wan in alleviating ulcerative colitis: Involvement of gut microbiota, SCFAs, and serum metabolites.

Abstract

OBJECTIVE: Ulcerative colitis (UC) involves barrier disruption, dysbiosis, and altered host-microbe metabolism. Zuojin Wan (ZJW) benefits gastrointestinal disorders, but its systems-level mechanisms in UC are unclear. METHODS: In DSS-induced UC mice, ZJW chemistry was profiled by HPLC-MS, and efficacy was assessed by DAI, colon length, histology, and serum cytokines. Mechanistic assays included 16S sequencing, GC-MS SCFA quantification, serum metabolomics, tight-junction immunohistochemistry, and FMT from ZJW-treated donors. RESULTS: ZJW reduced DAI, protected colon structure, improved mucosal injury, and decreased IL-6, TNF-α, IL-1β, and IL-18. It corrected dysbiosis with increased beneficial taxa (e.g., Akkermansia), elevated SCFAs-especially propionic and n-pentanoic acids-and remodeled metabolites in glycerophospholipid and aromatic amino-acid pathways. SCFAs correlated with key serum metabolites. ZJW restored Claudin-5 and Occludin localization, and FMT transferred protection to depleted recipients. CONCLUSIONS: ZJW ameliorates colitis via a microbiota-SCFA-metabolic axis that suppresses inflammation and strengthens tight junctions, supporting its multi-target utility in UC.