BackgroundThis study investigated the protective effects of Anacyclus pyrethrum L. (AP) in a dextran sulfate sodium (DSS)-induced colitis mouse model and explored its potential associations with intestinal barrier function, inflammatory responses, gut microbiota, and fecal metabolic profiles.MethodsDSS-induced colitis mice were treated with different doses of AP aqueous extract. Disease activity, intestinal permeability, histopathological injury, inflammatory mediators, tight junction proteins, gut microbiota, and fecal metabolites were assessed.ResultsAdministration of AP mitigated clinical signs of IBD in murine models. AP suppressed the expression of the innate immune receptors TLR4 and TLR9, which are known to trigger inflammatory responses. In parallel, AP enhanced the expression of the tight junction proteins occludin and ZO-1 and was associated with restoration of intestinal barrier integrity. AP therapy was also associated with increased abundance of beneficial commensal bacterial taxa, including Bacteroides and Clostridiales_unclassified. Finally, non-targeted metabolomics analysis showed that AP intervention altered specific intestinal metabolites and affected related metabolic pathways, suggesting a multifaceted mechanism of action.ConclusionThese findings suggest that AP alleviates DSS-induced colitis in association with improved intestinal barrier function, reduced inflammatory responses, and modulation of gut microbiota composition and fecal metabolic profiles.