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Excessive mucosal ROS activate the TXNIP\/NLRP3 inflammasome axis, which in turn drives interleukin\u20101\u03b2\u2010mediated epithelial barrier disruption and dysbiosis. Conventional solid nanozymes suffer from limited catalytic efficiency because dense interiors restrict substrate access. Here, hollow cuprous oxide nanozymes (H\u2010Cu\n                    <jats:sub>2<\/jats:sub>\n                    O) are engineered to overcome these limitations. The hollow architecture exposes a larger catalytically accessible surface area, enabling H\u2010Cu\n                    <jats:sub>2<\/jats:sub>\n                    O to achieve broad\u2010spectrum reactive oxygen species scavenging with superior efficiency compared with its composition\u2010matched solid counterpart (S\u2010Cu\n                    <jats:sub>2<\/jats:sub>\n                    O). In mouse models of colitis, low\u2010dose H\u2010Cu\n                    <jats:sub>2<\/jats:sub>\n                    O (4\u00a0mg kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ) attenuates oxidative damage, suppresses the TXNIP\/NLRP3 cascade, and restores tight junction integrity. Furthermore, 16S rRNA sequencing reveals that H\u2010Cu\n                    <jats:sub>2<\/jats:sub>\n                    O remodels the dysbiotic gut microbiota toward homeostasis with Lactobacillus enrichment. Importantly, the sequential co\u2010administration of Lactiplantibacillus plantarum with H\u2010Cu\n                    <jats:sub>2<\/jats:sub>\n                    O outperforms the electrostatically assembled hybrid LP@H\u2010Cu\n                    <jats:sub>2<\/jats:sub>\n                    O, demonstrating that free nanozyme diffusion is more effective than surface immobilization for combination therapy. This work establishes hollow nanozyme architecture as a key determinant of anti\u2010inflammatory efficacy and validates nanozyme\u2010probiotic co\u2010delivery as a translatable IBD treatment strategy.\n                  <\/jats:p>","DOI":"10.1002\/advs.76598","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T12:23:46Z","timestamp":1784031826000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hollow Cu\n                    <sub>2<\/sub>\n                    O Nanozymes Enhance Probiotic Therapy for Colitis via Redox Homeostasis and TXNIP\/NLRP3 Inflammasome Inhibition"],"prefix":"10.1002","volume":"13","author":[{"given":"Guangzhao","family":"Wang","sequence":"first","affiliation":[{"name":"School of Life Sciences and Medical Engineering Anhui University  Hefei Anhui China"},{"name":"Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education 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