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To tackle this limitation, bioinformatic approaches are employed to predict that inflammation and metabolism may be potential targets for Fucoidan. Guided by this prediction, we develop oral polysaccharide engineered nanozymes, Fucoidan\u2010cerium nanocomplexes (FucCeNCs), which are capable of targeting the inflamed colon through electrostatic interactions, exerting anti\u2010inflammatory effects, and concurrently regulating gut microbiota\u2010derived metabolism. In a murine model of ulcerative colitis\u2010associated mental disorders, FucCeNCs show anti\u2010inflammatory and gut barrier\u2010protective effects, thereby suppressing microglial\/astrocytic overactivation and preserving neuronal integrity through the transmission of anti\u2010inflammatory cytokines via gut\u2013brain axis. Importantly, FucCeNCs restore gut microbial homeostasis through increasing the relative abundance of probiotics and reducing proportions of pathogens. This shift results in a marked attenuation of abnormal amino acid biosynthesis and metabolism in fecal metabolites, which in turn leads to elevated levels of bioactive metabolites such as homovanillic acid and \u03b3\u2010aminobutyric acid. These metabolites ultimately attenuate neuroinflammation via the microbiome\u2010gut\u2013brain axis, ameliorating depression\u2010 and anxiety\u2010like behaviors. These results identify microbiome\u2010gut\u2013brain axis as pivotal therapeutic target for colitis\u2010associated mental disorders therapy, which can be addressed by polysaccharide engineered nanozymes.<\/jats:p>","DOI":"10.1002\/adma.202522010","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T07:36:07Z","timestamp":1770017767000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Polysaccharide Engineered Nanozymes Target Inflammation for Alleviating Colitis\u2010Associated Mental Disorders via Microbiome\u2010Gut\u2013Brain Axis"],"prefix":"10.1002","volume":"38","author":[{"given":"Gen","family":"Wei","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine Faculty of Medicine Yangzhou University  Yangzhou Jiangsu China"},{"name":"Key Laboratory of the Jiangsu Higher Education Institutions for Integrated Traditional Chinese and Western Medicine in 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