Abstract

LJF treatment significantly alleviated DSS-induced colitis symptoms, reducing disease activity index, colon shortening, and histological damage. • LJF enhanced intestinal barrier integrity by upregulating tight junction protein Occludin and restoring mucosal immune homeostasis. • LJF modulated gut microbiota by enriching beneficial genera (e.g. g_Duncaniella , g_Alistipes_A ) while suppressing pathogenic g_Escherichia . • High-dose LJF increased SCFA-producing bacteria ( s_Alistipes , g_UBA7173 ) and upregulated putative metabolic pathways for antibiotic and glycan synthesis. • LJF ameliorates UC via dual mechanisms: reinforcing intestinal barrier function and regulating microbiota composition and predicted metabolic function. Ulcerative Colitis (UC) is a chronic inflammatory bowel disease characterized by recurrent inflammation of the colonic mucosa. In this study, a dextran sulfate sodium (DSS)-induced mouse model of UC was employed to investigate the protective effects of Laminaria japonica fucoidan (LJF) against UC, with a focus on elucidating its role in intestinal barrier repair and its modulatory effects on the gut microbiota. The results demonstrated that LJF treatment significantly reduced the disease activity index and spleen index in model mice, alleviated fecal bleeding, and ameliorated colon shortening. Histological analysis confirmed that LJF attenuated colonic tissue injury, upregulated the expression of the tight junction protein Occludin, reduced intestinal inflammation, and consequently enhanced intestinal barrier function. Gut microbiota analysis revealed that LJF enriched beneficial bacterial genera such as Duncaniella and Alistipes_A , while inhibiting the proliferation of the pathogenic Escherichia . In the high-dose LJF (H-LJF) group, short-chain fatty acid-producing bacteria, including Alistipes and UBA7173 , were identified as key biomarkers. Functional predictions using PICRUSt2 and FAPROTAX indicated that H-LJF downregulated