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

Nutr Res. 2024 Feb:122:1-18. doi: 10.1016/j.nutres.2023.11.009. Epub 2023 Nov 17.

Abstract

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.

Keywords: Autophagy; Fucoidan; Gut microbiota; Intestinal barrier; Ulcerative colitis.

MeSH terms

  • Animals
  • Autophagy
  • Bacteroidetes
  • Clostridiales
  • Colitis*
  • Colitis, Ulcerative* / chemically induced
  • Colitis, Ulcerative* / drug therapy
  • Colon
  • Dextran Sulfate
  • Disease Models, Animal
  • Gastrointestinal Microbiome*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Polysaccharides*

Substances

  • fucoidan
  • Dextran Sulfate
  • Polysaccharides