Jiawei Gegen Qinlian Decoction Ameliorates DSS-Induced Ulcerative Colitis by Restoring Intestinal Barrier Integrity Via the Gut Microbiota–Metabolite Axis

Ulcerative colitis (UC) is a multifactorial intestinal inflammatory disorder involving excessive immune activation, oxidative imbalance, epithelial barrier impairment, microbial disturbance, and metabolic dysregulation.Similar pathological alterations are commonly encountered in animal intestinal diseases, emphasizing the exploration of safe and effective natural therapeutics.This study aimed to clarify the protective actions and potential mechanisms of Jiawei Gegen Qinlian Decoction (JGQD) against dextran sulfate sodium (DSS)-induced colitis.A comprehensive strategy combining network pharmacology, in-vivo validation, 16S rRNA gene sequencing and UHPLC-MS metabolomics was applied to characterize the regulatory effects of JGQD on therapeutic targets, inflammatory status, oxidative damage, intestinal barrier function, microbial composition, and fecal metabolic alterations.Network analysis revealed that JGQD-associated targets were mainly involved in inflammation-regulating pathways, including TNF, NF-κB, PI3K-Akt, MAPK and JAK-STAT signaling cascades.In DSS-challenged mice, JGQD markedly decreased markedly by colonic TNF-α, IL-6, IL-1β, MDA and MPO levels, while enhancing IL-10 production, SOD activity and total antioxidant capacity.Moreover, JGQD restored tight junction protein expression (ZO-1, Occludin and Claudin-3), reshaped gut microbial composition with increased Akkermansia abundance and modulated metabolism associated with amino acids, bile acids and lipids.JGQD alleviated experimental colitis by regulating the interconnected microbiota-metabolite-intestinal barrier network, suggesting its potential application as a natural multi-component intervention for controlling intestinal inflammatory disorders and maintaining barrier homeostasis in veterinary medicine.