{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:44:00Z","timestamp":1790793840708,"version":"4.1.0"},"reference-count":131,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Ulcerative colitis (UC), a chronic inflammatory bowel disease driven by gut dysbiosis, immune dysregulation, and oxidative stress, lacks universally effective therapies. Fucoidan (FCD), a sulfated polysaccharide derived from brown algae, has emerged as a multifaceted therapeutic candidate due to its anti-inflammatory, antioxidant, and immunomodulatory properties. This review synthesizes FCD\u2019s mechanisms in UC pathogenesis, emphasizing its suppression of NF-\u03baB and MAPK signaling pathways to reduce proinflammatory cytokines (e.g., IL-6, TNF-\u03b1) and regulate TLR-mediated macrophage polarization. FCD enhances intestinal barrier integrity via upregulation of tight junction proteins (Claudin-1, ZO-1) and mucin MUC2 expression, while remodeling gut microbial ecology through enrichment of SCFAs-producing bacteria (e.g., Ruminococcaceae) and suppression of pathogens (Escherichia coli, Candida albicans). Preclinical studies highlight LMWF as a superior candidate, demonstrating enhanced bioavailability and efficacy in mitigating DSS-induced colitis. Despite its promise, challenges persist in structural heterogeneity (source- and extraction-dependent), scalable production of LMWF, and insufficient pharmacokinetic data. Emerging strategies\u2014including nanoparticle-based delivery systems and structural modifications (cross-linking, covalent bonding)\u2014aim to overcome bioavailability limitations. This review underscores FCD\u2019s potential as a functional food or adjuvant therapy for UC, while advocating for rigorous clinical validation to bridge translational gaps, Enrichment of SCFAs-producing taxa and suppression of pathobionts (<jats:italic>Escherichia coli<\/jats:italic>, <jats:italic>Candida albicans<\/jats:italic>), mediated through prebiotic fermentation. Suppression of NF-\u03baB activation via I\u03baB\u03b1 stabilization and inhibition of p65 nuclear translocation, and downregulation of MAPK phosphorylation (ERK1\/2, JNK, p38), reducing proinflammatory cytokines (IL-6, TNF-\u03b1, IL-1\u03b2). FCD can be used as a potential treatment for UC.<\/jats:p>","DOI":"10.3389\/fcimb.2025.1626614","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T05:32:04Z","timestamp":1752125524000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":16,"title":["Fucoidan as a therapeutic agent for ulcerative colitis: mechanisms of action and modulation of the gut microbiota"],"prefix":"10.3389","volume":"15","author":[{"given":"Yating","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"702","DOI":"10.3390\/md19120702","article-title":"Anti-inflammatory activity of fucoidan extracts in vitro","volume":"19","author":"Ahmad","year":"2021","journal-title":"Mar. 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