Structural Characteristics of Low-Molecular-Weight Fucoidan and Its Protective Effects on DSS-Induced Colitis and Associated Behavioral Abnormalities by Improving Intestinal Homeostasis

This study characterized low-molecular-weight fucoidan (Degradation Laminaria japonica fucoidan (DLJF)) and evaluated its protective effects against dextran sulfate sodium (DSS)-induced colitis. Structural characterization revealed that DLJF had a molecular weight of 40.64 kDa and was a fucose-rich sulfated heteropolysaccharide predominantly composed of sulfated α-L-Fucp residues, with minor α-D-Manp and α-D-Glcp units. DLJF administration markedly alleviated colitis and suppressed pro-inflammatory factors, possibly through the modulation of the Toll-like receptor 4/NF-κB pathway. It also improved intestinal barrier integrity by upregulating ZO - 1 and occludin. Furthermore, DLJF was associated with alterations in gut microbiota composition, including increased relative abundances of Akkermansia muciniphila, Muribaculaceae, Bacteroides, and Alistipes, and elevated levels of short-chain fatty acids, including acetic, propionic, and butyric acids. Metabolomics analysis identified cholic acid, xanthine, inosine, and pantothenic acid as key metabolites following DLJF supplementation. Notably, DLJF attenuated DSS-induced brain inflammatory responses and was associated with partial improvement in colitis-associated behavioral abnormalities. These findings highlight DLJF as a potential functional food ingredient for colitis management.