Taoling Yuyang Decoction alleviates DSS-induced ulcerative colitis in mice by regulating gut microbiota -metabolite axis and restore intestinal barrier function.

BACKGROUND

Traditional Chinese medicine (TCM) offers multi-targeted therapy with few side effects for ulcerative colitis (UC). Taoling Yuyang Decoction (TLYY) has shown clinical efficacy, however, its mechanisms of action are unclear. This study employed a multi-omics approach to elucidate TLYY's therapeutic effects in a murine DSS-induced colitis model.

METHODS

Using a DSS-induced mouse model of colitis, animals were divided into five groups (n = 8): blank control (CK), model (DSS), low- and high-dose TLYY (TLYYL, TLYYH), and positive control (5-ASA). Treatment efficacy was assessed by measuring body weight, disease activity index (DAI), and histopathological changes. Oxidative stress markers (MDA, GSH-Px, SOD) in serum and colon tissues were quantified using commercial kits and immunohistochemistry. Cytokine levels (IL-1β, TNF-α, IL-6) and LPS were measured by ELISA. The expression of tight junction proteins (ZO-1, Occludin, Claudin-1) in colon tissue was analyzed via qPCR and immunocytochemistry. Additionally, 16S rDNA sequencing and metabolomics were employed to examine gut microbiota composition, fecal SCFAs, and differential metabolites.

RESULTS

Taoling Yuyang Decoction treatment dose-dependently alleviated UC symptoms, including weight loss, colon shortening, and tissue damage. It enhanced antioxidant activities (SOD, GSH-Px) and reduced MDA, suppressed pro-inflammatory cytokines and LPS, and up-regulated tight junction proteins (ZO-1, Occludin, Claudin-1). Gut microbiota analysis showed TLYY-H restored microbial diversity, increased beneficial bacteria (e.g., Lactobacillus, Akkermansia), and decreased harmful genera (e.g., Helicobacter). It also elevated SCFA levels and modulated fecal metabolism, up-regulating anti-inflammatory/antioxidant metabolites while down-regulating toxic compounds. Key pathways such as AGE-RAGE signaling and xenobiotic metabolism were restored.

CONCLUSION

Taoling Yuyang Decoction ameliorates DSS-induced colitis via integrated mechanisms involving oxidative stress reduction, anti-inflammation, intestinal barrier repair, and restoration of gut flora homeostasis and metabolic pathways. The superior effect of the high dose highlights its clinical potential for UC treatment.