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This coordination chemistry transforms the binary polyphenols into a stable, quasi\u2010amorphous state, substantially enhancing their aqueous dispersibility and gastrointestinal stability. Benefiting from this structural evolution, ZnCA NPs exhibited superior colonic accumulation and efficient reactive oxygen and nitrogen species scavenging. In zebrafish and murine colitis models, ZnCA NPs effectively reinforced the mucosal barrier and mitigated microenvironmental inflammation. Mechanistically, transcriptomic profiling revealed that ZnCA NPs modulated the colonic microenvironment by downregulating core NF\u2010\u03baB, MAPK, and JAK\u2010STAT signaling cascades. Crucially, ZnCA NPs enriched beneficial commensals, most prominently Muribaculaceae, to attenuate dextran sulfate sodium\u2010induced dysbiosis; the functional contribution of this remodeled microbiota in maintaining colonic homeostasis was microbiota transplantation. This study transitions polyphenol nanomedicine from fragile physical self\u2010assembly to robust metal\u2013phenolic coordination for enhanced prevention of intestinal inflammation.\n                  <\/jats:p>","DOI":"10.1002\/advs.77647","type":"journal-article","created":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:00:31Z","timestamp":1790532031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Supramolecular Zinc\u2013Polyphenol Coordination Assemblies Mitigate Colonic Inflammation by Regulating Mucosal Barrier and Microbiome"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5303-2386","authenticated-orcid":false,"given":"Qiwen","family":"Xie","sequence":"first","affiliation":[{"name":"State Key Laboratory of Food Science and Resources Nanchang University  Nanchang 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