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The non\u2010specific delivery of probiotics severely restricts their therapeutic efficacy. Herein, we developed a sustainable, food\u2010grade microgel delivery platform assembled from corncob nanocellulose building blocks with distinct geometries for programmable intestinal probiotic release. Owing to their distinct topological structures and mechanical properties, spherical nanocellulose\u2010based microgels (CNSM) were found to disintegrate in the ileum, while rod\u2010like nanocellulose\u2010based microgels (CNRM) retained intact until reaching the colon, where they subsequently ruptured. Molecular dynamics simulations supported the superior structural stability of CNRM against osmotic swelling, revealing a structure\u2010mechanics driven mechanism for the controlled release pattern. Both microgels significantly enhanced probiotic survival, as well as nanocoating\u2010mediated mucoadhesion and colonization. To maximize functionality, bile salt hydrolase\u2010producing\n                    <jats:italic>L. plantarum<\/jats:italic>\n                    WCFS1 and immunomodulatory\n                    <jats:italic>L. rhamnosus<\/jats:italic>\n                    GG were embedded into CNSM and CNRM, respectively. Consequently, ileum\u2010targeted WCFS1@CNSM significantly ameliorated hypercholesterolemia, accompanied by increased fecal cholesterol excretion and potential modulation of the gut\u2010liver signaling axis whereas colon\u2010targeted LGG@CNRM profoundly alleviated DSS\u2010induced colitis through epithelial barrier restoration and inflammation suppression. This work provides a region\u2010specific delivery strategy for next\u2010generation probiotic therapeutics.\n                  <\/jats:p>","DOI":"10.1002\/adma.75011","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:58:37Z","timestamp":1789966717000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Geometry\u2010Mediated Microgel Structure\u2010Mechanics for Intestinal Region\u2010Specific Probiotic Delivery"],"prefix":"10.1002","author":[{"given":"Shanan","family":"Chen","sequence":"first","affiliation":[{"name":"Research Center of Food Colloids and Delivery of Functionality College of Food Science and Nutritional Engineering China Agricultural University  Beijing P.R. 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