Fucoidan alleviated dextran sulfate sodium–induced ulcerative colitis with improved intestinal barrier, reshaped gut microbiota composition, and promoted autophagy in male C57BL/6 mice

•Fucoidan ameliorated dextran sulfate sodium-induced ulcerative colitis through promoting autophagy.•Fucoidan-induced autophagy improved colon barrier and reshaped gut microbiota.•The present study supported the therapeutic potential of fucoidan for the adjuvant treatment of other autophagy-related diseases. Although previous research has unveiled the remedial effects of fucoidan, an extract from marine algae, on ulcerative colitis (UC), the precise mechanisms remain elusive. Animal studies have suggested a connection between autophagy and the beneficial influences of fucoidan intervention. We hypothesized that fucoidan's alleviative effects on dextran sulfate sodium (DSS)-induced UC could be ascribed to autophagy. For our study, we chose 36 male C57BL/6 mice and administered 100 or 400 mg/(kg/body weight/day) of fucoidan via gavage for 5 consecutive weeks. During the last week, the mice were given 3% DSS in drinking water to induce UC. In contrast to the DSS-induced UC model, fucoidan intervention prevented DSS-induced body weight loss, mitigated colon shortening, improved colon mucosa damage, enhanced the intestinal barrier, and reduced serum inflammatory factor concentrations. Furthermore, fucoidan intervention reshaped the gut microbiota compositions, increased the relative abundance of Bacteroidota, Muribaculaceae_unclassified, Clostridiales_unclassified, and Lachnospiraceae_NK4A136_group, and decreased the relative abundance of Firmicutes, Proteobacteria, and Escherichia-Shigella, which led to a lower Firmicutes/Bacteroidota ratio. Additionally, fucoidan treatment enhanced autophagy, as evidenced by upregulated protein expressions of BECLIN1, ATG5, ATG7, and an increased microtubule-associated-proteinlight-chain-3-II/microtubule-associated-proteinlight-chain-3-I ratio. Our findings corroborated the ameliorating effects of fucoidan intervention on DSS-induced UC through autophagy activation, reorganization of gut microbiota, and fortification of the intestinal barrier. This lends support to the therapeutic potential of fucoidan as a natural bioactive ingredient for future UC treatments in humans. Rapidly increasing incidence of UC imposed an enormous burden on health care. The aim of this study was to investigate the potential mechanisms of fucoidan to ameliorate DSS-induced UC. Fucoidan treatments improved the intestinal barrier, regulated gut microbiota composition, decreased serum inflammatory factors concentrations, and promoted autophagy by inhib