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Current interventions often overlook the cascade nature of reactive oxygen species (ROS) generation in driving intestinal and systemic inflammation. Herein, a valence\u2010engineered CeO\n                    <jats:sub>X<\/jats:sub>\n                    \u2010based nanozyme with self\u2010cascade catalytic activity is developed, mimicking sequential oxidase\u2010superoxide dismutase\u2010peroxidase functions to enable continuous ROS scavenging while minimizing oxygen generation. By precisely tuning Ce\n                    <jats:sup>3+<\/jats:sup>\n                    \/Ce\n                    <jats:sup>4+<\/jats:sup>\n                    ratios from 0.27 to 0.93 through Au deposition (0.23 wt.%\u21925.2 wt.%), Dual functionality is achieved: 1) enhanced oxygen vacancy generation (71.4%) for efficient ROS scavenging via superoxide anion\u2192hydrogen peroxide\u2192hydroxide ion conversion, and 2) suppressed oxygen production to maintain the anaerobic microenvironment essential for gut microbiota. Encapsulating the nanozyme with sodium alginate (SA) to form Au\/CeO\n                    <jats:sub>X<\/jats:sub>\n                    (0.93)@SA ensures resistance to gastric acid upon oral administration. In RA model rats, this strategy restored gut microbial balance, normalized short\u2010chain fatty acid profiles, and significantly attenuated joint inflammation and cartilage degradation. The therapeutic efficacy is further evidenced by reduced systemic pro\u2010inflammatory cytokine levels and improved intestinal barrier integrity. This study established a design paradigm for gut microenvironment\u2010adapted nanozymes, offering a dual\u2010action strategy for early RA intervention through synchronized ROS elimination and microbiota homeostasis restoration.\n                  <\/jats:p>","DOI":"10.1002\/advs.202512281","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T04:12:58Z","timestamp":1759205578000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Structure\u2010Tailoring Cerium Nanozymes with Self\u2010Cascade ROS Scavenging Catalysis Modulate the Microbiota\u2010Gut\u2010Joint Axis for Rheumatoid Arthritis Therapy"],"prefix":"10.1002","volume":"12","author":[{"given":"Ge","family":"Wang","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences Xinxiang Medical University School of Pharmacy Xinxiang Medical University The First Affiliated Hospital of Xinxiang Medical University  Xinxiang 453007 P. 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianjun","family":"Ni","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Xinxiang Medical University School of Pharmacy Xinxiang Medical University The First Affiliated Hospital of Xinxiang Medical University  Xinxiang 453007 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Green Chemical Media and Reactions Ministry of Education Henan Key Laboratory of Organic Functional Molecule and Drug Innovation School of Chemistry and Chemical Engineering Henan Normal University  Xinxiang 453007 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8064-357X","authenticated-orcid":false,"given":"Weisheng","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive Interventional Radiology The Second Affiliated Hospital School of Biomedical Engineering Guangzhou Medical University  Guangzhou 510260 P. R. 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