Abstract
OBJECTIVES: The main purpose of this study was to evaluate the potential preventive effect of Total Flavonoids from Sea Buckthorn Leaves (Fla) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice from an integrated perspective of "gut microbiota-host interaction," and to elucidate its regulatory mechanism within the microbiota-metabolite-barrier-immune axis. METHODS: A DSS-induced UC mouse model was established, and mice were randomly assigned into normal control, model, mesalazine, and Fla low, middle, and high-dose groups. Disease severity, colonic barrier integrity, inflammatory cytokines, gut microbiota composition, and short-chain fatty acid levels were evaluated using histopathological, molecular biological, and metabolomic analyses. RESULT: Fla significantly ameliorated colonic damage and other pathological symptoms. It enhanced intestinal barrier integrity by upregulating ZO-1, E-cadherin, and MUC2 expression and suppressed inflammation by reducing TNF-α and IL-6 levels. Furthermore, Fla reshaped gut microbiota, increasing beneficial Akkermansia abundance, and elevated short-chain fatty acid (SCFA) production, with the most pronounced effects observed at the middle dose. CONCLUSIONS: In summary, in this preventive model, Fla synergistically enhances intestinal barrier function and suppresses excessive local inflammatory responses by reshaping the gut microbiota and promoting SCFA production, ultimately alleviating UC. This study provides scientific evidence for the high-value utilization of sea buckthorn leaves (a by-product) and offers new insights for developing microbiome-based preventive strategies for UC.