Sarcandra glabra alleviates intestinal injury via modulating gut microbiota and suppressing the IL-6/SOCS3 signaling...

Ulcerative colitis (UC) is a refractory inflammatory bowel disease characterized by gut microbiota dysbiosis and mucosal barrier disruption. Sarcandra glabra (Sg), a traditional herbal tea and dietary supplement, has been widely used to alleviate intestinal inflammation; however, its gut microbiota-dependent mechanism remains insufficiently clarified. In this study, Sg at 2, 4, and 8 g/kg was found to dose-dependently mitigate dextran sulfate sodium (DSS)-induced colitis in mice, restore mucosal barrier integrity by upregulating tight junction proteins and enhancing mucin secretion, and reduce serum levels of IL-1β, TNF-α, and IL-6. Integrative analysis of full-length 16S rRNA gene sequencing, transcriptomics, and metabolomics data revealed that Sg reshaped gut microbiota, selectively enriching Ligilactobacillus animalis while depleting Escherichia coli and Proteus vulgaris. We identified 8 microbiota-derived metabolites correlated with Ligilactobacillus animalis abundance, among which 2,3-dihydroxybenzoic acid (2,3-DHBA) exhibited the strongest protective effect against DSS-induced NCM460 cell damage. Mechanistic studies indicated that 2,3-DHBA effectively inhibited the IL-6/SOCS3 pathway and restored tight junction protein expression, effects that were reversed by exogenous IL-6. These findings demonstrate that Sg enriches for Ligilactobacillus animalis and its metabolite 2,3-DHBA, which suppresses IL-6-driven inflammation and repairs mucosal damage, supporting its potential as a microbiome-targeted dietary adjunct for UC.