Sea buckthorn pulp oil ameliorates colitis by enriching microbial fumaric acid and promoting SOX9/β-catenin-associated epithelial regeneration

Sea buckthorn pulp oil (SBO), a functional dietary lipid enriched in palmitoleic acid, has shown promise in maintaining intestinal homeostasis, yet the precise microbiota-host mechanisms underlying its beneficial effects remain elusive. Here, we show that daily prophylactic supplementation with SBO (300 mg/kg) alleviates dextran sulfate sodium (DSS)-induced colitis in mice by suppressing inflammation and preserving mucosal barrier integrity. Fecal microbiota transplantation into germ-free mice indicates that SBO-modulated gut microbiota is sufficient to transfer a substantial part of the protective effect of SBO. Integrated multi-omics analysis and in vitro anaerobic fermentation assays reveal that SBO remodels the gut microbiome and significantly enhances microbial fumaric acid production. Oral administration of fumaric acid alone reproduces the barrier-protective effects of SBO and promotes crypt epithelial proliferation in vivo. Ex vivo organoid culture and whole-transcriptome sequencing further indicate that fumaric acid enhances the regenerative capacity of the intestinal epithelial compartment, accompanied by activation of canonical Wnt/β-catenin signaling and upregulation of SOX9. Our findings delineate an SBO–microbiota–fumaric acid axis that is associated with epithelial regeneration, supporting further evaluation of SBO as a mechanism-based adjunctive nutritional strategy for intestinal inflammation.