Phenolic-Rich Extract from Pyracantha fortuneana Fruit Alleviates DSS-Induced Colitis in Mice: Insights from Gut Microbiota, Metabolomic, and Transcriptomic Analyses

Pyracantha fortuneana (Maxim.) H.L.Li fruit is a bioactive dietary resource, yet its effects on intestinal inflammation and the associated microbial, metabolic, and host responses remain poorly understood. This study characterized P. fortuneana fruit extract (PFE) and evaluated its protective effects in a dextran sodium sulfate (DSS)-induced colitis model using microbiota, metabolomic, and transcriptomic analyses. Chemical profiling confirmed the presence of representative phenolic acids, flavonoids, and condensed tannins in PFE. Administered before and during 2.5% DSS exposure, PFE reduced disease activity, attenuated colon shortening and the elevated spleen index, and improved colonic histopathological appearance. PFE also reduced IL-6 and increased IL-10 and serum GSH-Px levels, while high-dose PFE decreased TNF-α. It restored ZO-1 expression, increased colonic diamine oxidase levels, and tended to increase Occludin expression. PFE increased microbial diversity and evenness, reduced Turicibacter and Ruminococcus, and increased Prevotella and Jeotgalicoccus. Non-targeted metabolomics identified changes in selected cecal bile acid- and lipid-related metabolites, whereas transcriptomic and protein analyses implicated bile secretion- and PPAR-related responses, accompanied by increased ASBT, PPARγ, and NLRP6 expression. Collectively, these findings demonstrate the protective effects of PFE against DSS-induced colitis and support its further investigation as a potential food-derived bioactive ingredient for intestinal health.