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Here, we present a human immunocompetent colitis\u2010on\u2010chip model (CooC) that mimics key features of inflamed gut mucosa, including DSS\u2010induced epithelial damage and\n                    <jats:italic>C. albicans<\/jats:italic>\n                    tissue invasion. Using this model, we uncover dual protective roles of microbiota\u2010derived butyrate: (i) stabilization of epithelial adherens junctions and promotion of epithelial renewal, thereby restricting fungal invasion; and (ii) modulation of macrophage function to enhance antifungal activity while attenuating inflammasome\u2010mediated inflammation. Butyrate pretreatment preserves barrier function, limits fungal translocation, and promotes macrophage viability through the inhibition of histone deacetylase (HDAC) and the suppression of NLRP3 inflammasome activation. These findings position butyrate as a key metabolite in orchestrating epithelial\u2010immune defense against fungal exacerbation in colitis, supporting its therapeutic and preventive potential in restoring mucosal resilience in IBD.\n                  <\/jats:p>","DOI":"10.1002\/smll.202600074","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T09:45:27Z","timestamp":1778838327000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Human Colitis\u2010on\u2010Chip Model Reveals Dual Roles of Butyrate in Epithelial and Macrophage Defense Against\n                    <i>Candida albicans<\/i>\n                    Tissue Invasion"],"prefix":"10.1002","volume":"22","author":[{"given":"Manuel","family":"Allwang","sequence":"first","affiliation":[{"name":"Institute of Biochemistry II Jena University Hospital  Jena Germany"},{"name":"Cluster of Excellence Balance of the Microverse Friedrich Schiller University  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Wipplinger","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry II Jena University Hospital  Jena Germany"},{"name":"Cluster of Excellence Balance of the Microverse Friedrich Schiller University  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parastoo","family":"Akbarimoghaddam","sequence":"additional","affiliation":[{"name":"Cluster of Excellence Balance of the Microverse Friedrich Schiller University  Jena Germany"},{"name":"Applied Systems Biology Leibniz Institute for Natural Product Research and Infection Biology Hans Kn\u00f6ll Institute (HKI)  Jena Germany"},{"name":"Faculty of Biological Sciences Friedrich Schiller University  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Alonso\u2010Roman","sequence":"additional","affiliation":[{"name":"Cluster of Excellence Balance of the Microverse Friedrich Schiller University  Jena Germany"},{"name":"Junior Research Group Adaptive Pathogenicity Strategies Leibniz Institute for Natural Product Research and Infection Biology Hans Kn\u00f6ll Institute (HKI)  Jena Germany"},{"name":"Department of Microbial Pathogenicity Mechanisms Leibniz Institute for Natural Product Research and Infection Biology Hans Kn\u00f6ll Institute (HKI)  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoltan","family":"Cseresnyes","sequence":"additional","affiliation":[{"name":"Applied Systems Biology Leibniz Institute for Natural Product Research and Infection Biology Hans Kn\u00f6ll Institute (HKI)  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Dietschmann","sequence":"additional","affiliation":[{"name":"Junior Research Group Adaptive Pathogenicity Strategies Leibniz Institute for Natural Product Research and Infection Biology Hans Kn\u00f6ll Institute (HKI)  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Wegner","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry II Jena University Hospital  Jena Germany"},{"name":"Cluster of Excellence Balance of the Microverse Friedrich Schiller University  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Feile","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry II Jena University Hospital  Jena Germany"},{"name":"Cluster of Excellence Balance of the Microverse Friedrich Schiller University  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yann","family":"Bachelot","sequence":"additional","affiliation":[{"name":"Applied Systems Biology Leibniz Institute for Natural Product Research and Infection Biology Hans Kn\u00f6ll Institute (HKI)  Jena Germany"},{"name":"Faculty of Biological Sciences Friedrich Schiller University  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Warschinke","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry II Jena University Hospital  Jena Germany"},{"name":"Cluster of Excellence Balance of the Microverse Friedrich Schiller University  Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed I. 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