{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T16:30:50Z","timestamp":1790353850720,"version":"4.1.0"},"reference-count":39,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T00:00:00Z","timestamp":1739491200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020","award":["812969"],"award-info":[{"award-number":["812969"]}]},{"name":"European Union\u2019s Horizon 2020","award":["IK17088"],"award-info":[{"award-number":["IK17088"]}]},{"name":"European Union\u2019s Horizon 2020","award":["NGFOP2201"],"award-info":[{"award-number":["NGFOP2201"]}]},{"DOI":"10.13039\/501100003195","name":"Ministry of Economic Affairs and Climate of The Netherlands","doi-asserted-by":"publisher","award":["812969"],"award-info":[{"award-number":["812969"]}],"id":[{"id":"10.13039\/501100003195","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003195","name":"Ministry of Economic Affairs and Climate of The Netherlands","doi-asserted-by":"publisher","award":["IK17088"],"award-info":[{"award-number":["IK17088"]}],"id":[{"id":"10.13039\/501100003195","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003195","name":"Ministry of Economic Affairs and Climate of The Netherlands","doi-asserted-by":"publisher","award":["NGFOP2201"],"award-info":[{"award-number":["NGFOP2201"]}],"id":[{"id":"10.13039\/501100003195","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Oncode Accelerator","award":["812969"],"award-info":[{"award-number":["812969"]}]},{"name":"Oncode Accelerator","award":["IK17088"],"award-info":[{"award-number":["IK17088"]}]},{"name":"Oncode Accelerator","award":["NGFOP2201"],"award-info":[{"award-number":["NGFOP2201"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Candida albicans is an opportunistic pathogenic yeast commonly found in the gastrointestinal tract of healthy humans. Under certain conditions, it can become invasive and cause life-threatening systemic infections. One mechanism used by C.albicans to breach the epithelial barrier is the secretion of candidalysin, a cytolytic peptide toxin. Candidalysin damages epithelial membranes and activates the innate immune response, making it key to C.albicans\u2019 pathogenicity and a promising therapeutic target. Although candidalysin mediates C. albicans translocation through intestinal layers, its impact on epithelial responses is not fully understood. This study aims to characterize this response and develop scalable, quantitative methodologies to assess candidalysin\u2019s toxicological effects using gut-on-chip models. We used the OrganoPlate\u00ae platform to expose Caco-2 tubules to candidalysin and evaluated their response with trans-epithelial electrical resistance (TEER), protein detection, and immunostaining. We then validated our findings in a proof-of-concept experiment using human intestinal organoid tubules. Candidalysin impaired barrier integrity, induced actin remodeling, and increased cell permeability. It also induced the release of LDH, cytokines, and the antimicrobial peptide LL37, suggesting cellular damage, inflammation, and antimicrobial activity. This study strengthens our understanding of candidalysin\u2019s role in C. albicans pathogenesis and suggests new therapeutic strategies targeting this toxin. Moreover, patient-derived organoids show promise for capturing patient heterogeneity and developing personalized treatments.<\/jats:p>","DOI":"10.3390\/toxins17020089","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T03:20:52Z","timestamp":1739503252000},"page":"89","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Breaking Barriers: Candidalysin Disrupts Epithelial Integrity and Induces Inflammation in a Gut-on-Chip Model"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0262-7221","authenticated-orcid":false,"given":"Moran","family":"Morelli","sequence":"first","affiliation":[{"name":"MIMETAS B.V., De Limes 7, 2342 DH Oegstgeest, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla","family":"Queiroz","sequence":"additional","affiliation":[{"name":"MIMETAS B.V., De Limes 7, 2342 DH Oegstgeest, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1038\/s41422-020-0332-7","article-title":"Interaction between microbiota and immunity in health and disease","volume":"30","author":"Zheng","year":"2020","journal-title":"Cell Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"165rv13","DOI":"10.1126\/scitranslmed.3004404","article-title":"Hidden killers: Human fungal infections","volume":"4","author":"Brown","year":"2012","journal-title":"Sci. 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