A sulfated polysaccharide from Laminaria japonica alleviated colitis via remodeling gut microbiota and promoting butyrate-mediated barrier repair.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by dysregulated immunity, gut barrier dysfunction, and microbial dysbiosis. Polysaccharides from Laminaria japonica have shown anti-inflammatory properties and microbial-modulating potential, but their precise protective mechanisms, particularly through an integrated "microbiota-metabolite-barrier-inflammation" axis, remain unclear. In this study, a sulfated polysaccharide (ALP) was extracted from L. japonica and its protective effects were evaluated in a DSS-induced colitis mice model. ALP administration significantly alleviated disease severity, colon shortening, and tissue damage. Multi-omics analysis revealed that ALP uniquely enriched beneficial genera such as norank_f_Muribaculaceae, norank_o__Clostridia_UCG-014 and norank_o_RF39 while suppressing unclassified_f__Enterobacteriaceae, a shift distinct from conventional probiotics. This remodeling was associated with increased production of short-chain fatty acids, particularly butyrate. Concurrently, ALP enhanced intestinal barrier integrity by upregulating tight junction proteins (ZO-1, Occludin) and MUC-2 expression, thereby reducing endotoxin translocation and subsequently lowered systemic levels of TNF-α, IL-6, and IL-1β. Colon transcriptomics further confirmed the downregulation of key inflammatory pathways. Collectively, these results demonstrated that ALP alleviates UC via a coordinated multi-target network involving gut microbiota reprogramming, SCFAs production, barrier reinforcement, and inflammatory suppression. This study provides a mechanistic basis for the application of L. japonica polysaccharides as marine-based functional ingredient in gut health.