Gastrodin ameliorates DSS-induced ulcerative colitis via enhancing the abundance of Akkermansia muciniphila and modulating the metabolites

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory condition of the colon. Gastrodia elata Blume (G. elata), a traditional herbal medicine from the Orchidaceae family, has notable anti-inflammatory effects. But its treatment potential and underlying mechanisms in UC have not been fully elucidated. PURPOSE: This study was undertaken to investigate the underlying protective mechanisms of G. elata extract and its primary bioactive component, gastrodin (GAS), against UC. METHODS: The colitis mice model was developed through DSS drinking and oral treatment with G. elata extract and GAS. 16S rRNA was performed to investigate the mechanisms associated with the gut microbiota, while untargeted metabolomics was employed to assess alterations in metabolic pathway profiles. RESULTS: G. elata extract demonstrated significant efficacy in alleviating colitis symptoms, with GAS identified as its principal active constituent. The results indicated that GAS exerts its protective effected in a manner closely related to the gut microbiota. Analysis of 16S rRNA revealed GAS specifically enriched A. muciniphila populations. Subsequent administration of live A. muciniphila recapitulated the anti-colitis effects of GAS. Metabolomic profiling revealed 19 co-upregulated metabolites, with cucurbitacin E and antcin K identified as key metabolites within the pathways modulated by A. muciniphila. CONCLUSIONS: G. elata ameliorated colitis through a novel 'herbal monomer‒microbiota‒metabolite' axis, enriching A. muciniphila and enhancing the levels of key anti-inflammatory metabolites. These findings provided evidence the traditional application of G. elata and its active ingredient GAS as a promising microbiota-targeting therapy for UC.