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In this study, structurally modified\n                    <jats:italic>Cyclocarya paliurus<\/jats:italic>\n                    polysaccharide (CP) derivatives were evaluated in a dextran sulfate sodium (DSS)\u2010induced UC mouse model. Among the variants tested, sulfated\n                    <jats:italic>Cyclocarya paliurus<\/jats:italic>\n                    polysaccharide (SCP) emerged as the most therapeutically potent. SCP administration markedly attenuated colitis severity, as evidenced by relieved disease symptoms and reinforced intestinal barrier function. Mechanistically, SCP restored gut microbial homeostasis by enriching beneficial\n                    <jats:italic>Bacteroidetes<\/jats:italic>\n                    and enhancing short\u2010chain fatty acids (SCFAs) production. This remodeled microbial ecosystem orchestrates the upregulation of host\u2010derived 12\u2010hydroxyeicosapentaenoic acid (12\u2010HEPE), which exerts anti\u2010inflammatory effects via direct inhibition of Toll\u2010like receptor 4 (TLR4) signaling. The gut microbiota's functional relevance was substantiated by fecal microbiota transplantation and antibiotic\u2010mediated exhaustion studies. Notably, the therapeutic benefits of 12\u2010HEPE were abrogated upon co\u2010administration of a TLR4 agonist, confirming its target specificity. Elevated serum 12\u2010HEPE levels were observed in a human UC cohort, implying a potential compensatory immunoregulatory response. Our findings elucidate a novel microbiota\u2013host interaction axis wherein SCP alleviates UC by modulating the gut microbiota to enhance endogenous 12\u2010HEPE production, thereby suppressing TLR4\u2010mediated inflammation.\n                  <\/jats:p>","DOI":"10.1002\/advs.75681","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T15:11:18Z","timestamp":1778857878000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sulfated\n                    <i>Cyclocarya Paliurus<\/i>\n                    Polysaccharide Sorchestrates the Gut Microbiome to Mobilize a Host\u2010Derived 12\u2010HEPE Against Ulcerative Colitis"],"prefix":"10.1002","volume":"13","author":[{"given":"Xianxiang","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Science and Resources Nanchang University  Nanchang China"},{"name":"College of Food Science and Engineering Hainan 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