{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:21:23Z","timestamp":1793658083543,"version":"4.5.1"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T00:00:00Z","timestamp":1763510400000},"content-version":"vor","delay-in-days":18,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001636","name":"University College Cork","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001636","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Barrier healing is an emerging therapeutic target in inflammatory bowel disease (IBD), though its assessment remains challenging. We evaluated automated advanced imaging for real-time barrier assessment, its correlation with epithelial\/vascular barrier markers, and ability to predict adverse outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>IBD patients and healthy controls undergoing endoscopic assessment were prospectively enrolled. The intestinal barrier was evaluated using ultra-high-magnification endocytoscopy and probe-based confocal laser endomicroscopy. Targeted biopsies were obtained from inflamed and non-inflamed segments. Epithelial and vascular barriers were assessed through automated multiplex immunofluorescence for Claudin-2, ZO-1, E-cadherin, PV-1, and CD31. Gene expression profiling was performed in epithelial and lamina propria compartments. Artificial intelligence (AI)-based analysis was employed for automated evaluation of barrier features captured by advanced imaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In total, 103 patients were included (38 ulcerative colitis [UC], 54 Crohn\u2019s disease [CD], 11 healthy controls). Advanced imaging revealed barrier healing in 21% (8\/38) of UC and 30% (16\/54) of CD patients. In UC, Claudin-2 moderately correlated with abnormal crypt architecture (\u03c1\u2009=\u20090.49), goblet cell depletion (\u03c1\u2009=\u20090.5), and overall endocytoscopy activity (\u03c1\u2009=\u20090.49). In CD, PV-1 moderately correlated with altered blood flow (\u03c1\u2009=\u20090.41) and vessel architecture (\u03c1\u2009=\u20090.40). An integrated assessment of advanced imaging, combined with Claudin-2 and PV-1 expression, effectively predicted adverse outcomes in UC and CD, respectively. AI tools accurately classified epithelial and vascular barrier features captured by advanced imaging. Finally, gene expression confirmed upregulation of Claudin-2 and PV-1 in IBD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Automated advanced imaging enables real-time barrier assessment in IBD and correlates with markers of epithelial and vascular barrier impairment. AI integration can enhance standardization toward broader clinical applicability.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ecco-jcc\/jjaf200","type":"journal-article","created":{"date-parts":[[2025,11,16]],"date-time":"2025-11-16T12:55:59Z","timestamp":1763297759000},"source":"Crossref","is-referenced-by-count":17,"title":["Automated real-time imaging of intestinal barrier integrity and molecular profiling for early outcome prediction in inflammatory bowel disease: endo-histo-barrier-omics study"],"prefix":"10.1093","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3142-9550","authenticated-orcid":false,"given":"Marietta","family":"Iacucci","sequence":"first","affiliation":[{"name":"APC Microbiome Ireland, College of Medicine and Health, University College Cork , Cork,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snehali","family":"Majumder","sequence":"additional","affiliation":[{"name":"APC Microbiome Ireland, College of Medicine and Health, University College Cork , Cork,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Zammarchi","sequence":"additional","affiliation":[{"name":"APC Microbiome Ireland, College of Medicine and Health, University College Cork , Cork,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0544-0414","authenticated-orcid":false,"given":"Giovanni","family":"Santacroce","sequence":"additional","affiliation":[{"name":"APC Microbiome Ireland, College of Medicine and Health, University College Cork , Cork,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3927-591X","authenticated-orcid":false,"given":"Ivan","family":"Capobianco","sequence":"additional","affiliation":[{"name":"APC Microbiome Ireland, College of Medicine and Health, University College Cork , Cork,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6043-3231","authenticated-orcid":false,"given":"Cecilia Lina","family":"Pugliano","sequence":"additional","affiliation":[{"name":"APC Microbiome Ireland, College of Medicine and Health, University College Cork , Cork,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ujwala","family":"Chaudari","sequence":"additional","affiliation":[{"name":"School of Engineering, London South Bank University , London,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Meseguer Esbri","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n en Bioingenier\u00eda, HUMAN-Tech, Universitat Polit\u00e8cnica de Val\u00e8ncia , Val\u00e8ncia,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Hayes","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Cork University Hospital , Cork,","place":["Ireland"]},{"name":"Deparment of Pathology, University College Cork , Cork,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory","family":"Crotty","sequence":"additional","affiliation":[{"name":"Department of Histopathology, Cork University Hospital , Cork,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria R","family":"Aburto","sequence":"additional","affiliation":[{"name":"APC Microbiome Ireland, Department of Anatomy and Neuroscience\u2014School of Medicine, University College Cork , Cork,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Rocio","family":"del Amor","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n en Bioingenier\u00eda, HUMAN-Tech, Universitat Polit\u00e8cnica de Val\u00e8ncia , Val\u00e8ncia,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bisi Bode","family":"Kolawole","sequence":"additional","affiliation":[{"name":"School of Engineering, London South Bank University , London,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Eckenberger","sequence":"additional","affiliation":[{"name":"APC Microbiome Ireland, College of Medicine and Health, University College Cork , Cork,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Amamou","sequence":"additional","affiliation":[{"name":"APC Microbiome Ireland, College of Medicine and Health, University College Cork , Cork,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery","family":"Naranjo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n e Innovaci\u00f3n en Bioingenier\u00eda, HUMAN-Tech, Universitat Polit\u00e8cnica de Val\u00e8ncia , Val\u00e8ncia,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Grisan","sequence":"additional","affiliation":[{"name":"School of Engineering, London South Bank University , London,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1713-7797","authenticated-orcid":false,"given":"Subrata","family":"Ghosh","sequence":"additional","affiliation":[{"name":"APC Microbiome Ireland, College of Medicine and Health, University College Cork , Cork,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Endo-Histo-Barrier-Omics Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Puga-Tejada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Burke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"McCarthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Morales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,19]]},"reference":[{"key":"2025121401064432400_jjaf200-B1","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1136\/gutjnl-2023-329964","article-title":"Different levels of healing in inflammatory bowel diseases: mucosal, histological, transmural, barrier and complete healing","volume":"72","author":"Neurath","year":"2023","journal-title":"Gut"},{"key":"2025121401064432400_jjaf200-B2","doi-asserted-by":"crossref","first-page":"i421","DOI":"10.1093\/ecco-jcc\/jjae190.0235","article-title":"P0061 Guselkumab induction therapy results in molecular resolution of inflammation in moderately to severely active Ulcerative Colitis: results from the Phase 3 QUASAR induction study","volume":"19","author":"Sridhar","year":"2025","journal-title":"J Crohns Colitis"},{"key":"2025121401064432400_jjaf200-B3","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1053\/j.gastro.2022.10.014","article-title":"Intestinal barrier healing is superior to endoscopic and histologic remission for predicting major adverse outcomes in inflammatory bowel disease: the prospective ERIca trial","volume":"164","author":"Rath","year":"2023","journal-title":"Gastroenterology"},{"key":"2025121401064432400_jjaf200-B4","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1136\/gutjnl-2019-318427","article-title":"Leaky gut: mechanisms, measurement and clinical implications in humans","volume":"68","author":"Camilleri","year":"2019","journal-title":"Gut"},{"key":"2025121401064432400_jjaf200-B5","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1002\/ueg2.12677","article-title":"Epithelial neutrophil localization and tight junction Claudin-2 expression are innovative outcome predictors in inflammatory bowel disease","volume":"12","author":"Zammarchi","year":"2024","journal-title":"United European Gastroenterol J"},{"key":"2025121401064432400_jjaf200-B6","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1126\/science.aad0135","article-title":"A gut-vascular barrier controls the systemic dissemination of bacteria","volume":"350","author":"Spadoni","year":"2015","journal-title":"Science"},{"key":"2025121401064432400_jjaf200-B7","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1136\/gutjnl-2023-331579","article-title":"Opening the doors of precision medicine: novel tools to assess intestinal barrier in inflammatory bowel disease and colitis-associated neoplasia","volume":"73","author":"Iacucci","year":"2024","journal-title":"Gut"},{"key":"2025121401064432400_jjaf200-B8","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1136\/gutjnl-2024-332894","article-title":"Endocytoscopy with automated multispectral intestinal barrier pathology imaging for assessment of deep healing to predict outcomes in ulcerative colitis","volume":"73","author":"Majumder","year":"2024","journal-title":"Gut"},{"key":"2025121401064432400_jjaf200-B9","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/s41575-025-01051-1","article-title":"AI-enabled \u2018endo-histo-omics\u2019: breaking down intestinal barriers in IBD","volume":"22","author":"Iacucci","year":"2025","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2025121401064432400_jjaf200-B10","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/S2468-1253(24)00053-0","article-title":"Artificial intelligence and endo-histo-omics: new dimensions of precision endoscopy and histology in inflammatory bowel disease","volume":"9","author":"Iacucci","year":"2024","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"2025121401064432400_jjaf200-B11","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1093\/ibd\/izac233","article-title":"Computer-aided imaging analysis of probe-based confocal laser endomicroscopy with molecular labeling and gene expression identifies markers of response to biological therapy in IBD Patients: the endo-omics study","volume":"29","author":"Iacucci","year":"2023","journal-title":"Inflamm Bowel Dis"},{"key":"2025121401064432400_jjaf200-B12","doi-asserted-by":"crossref","first-page":"810858","DOI":"10.3389\/fmolb.2022.810858","article-title":"Validation of an accurate automated multiplex immunofluorescence method for immuno-profiling melanoma","volume":"9","author":"Yaseen","year":"2022","journal-title":"Front Mol Biosci"},{"key":"2025121401064432400_jjaf200-B13","article-title":"Protocol for Freezing in OCT","author":"Lin","year":"2020","journal-title":"Protocols.Io"},{"key":"2025121401064432400_jjaf200-B14","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/s42003-022-03368-y","article-title":"A framework for multiplex imaging optimization and reproducible analysis","volume":"5","author":"Eng","year":"2022","journal-title":"Commun Biol"},{"key":"2025121401064432400_jjaf200-B15","doi-asserted-by":"crossref","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci Rep"},{"key":"2025121401064432400_jjaf200-B16","doi-asserted-by":"crossref","first-page":"9","DOI":"10.4103\/jpi.jpi_82_18","article-title":"Introduction to digital image analysis in whole-slide imaging: a white paper from the Digital Pathology Association","volume":"10","author":"Aeffner","year":"2019","journal-title":"J Pathol Inform"},{"key":"2025121401064432400_jjaf200-B17","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1002\/0471221201.ch10","volume-title":"Culture of Epithelial Cells","author":"Booth","year":"2002"},{"key":"2025121401064432400_jjaf200-B18","doi-asserted-by":"crossref","first-page":"jjaf073","DOI":"10.1093\/ecco-jcc\/jjaf073","article-title":"ECCO topical review on predictive models on inflammatory bowel disease disease course and treatment response","volume":"19","author":"Kirchgesner","year":"2025","journal-title":"J Crohns Colitis"},{"key":"2025121401064432400_jjaf200-B19","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1053\/j.gastro.2020.12.031","article-title":"STRIDE-II: an update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): determining therapeutic goals for Treat-to-Target strategies in IBD","volume":"160","author":"Turner","year":"2021","journal-title":"Gastroenterology"},{"key":"2025121401064432400_jjaf200-B20","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1053\/j.gastro.2024.07.004","article-title":"Molecular mechanisms underlying loss of vascular and epithelial integrity in irritable bowel syndrome","volume":"167","author":"Barbaro","year":"2024","journal-title":"Gastroenterology"},{"key":"2025121401064432400_jjaf200-B21","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12876-021-02075-y","article-title":"The association of zonulin-related proteins with prevalent and incident inflammatory bowel disease","volume":"22","author":"Wang","year":"2022","journal-title":"BMC Gastroenterol"},{"key":"2025121401064432400_jjaf200-B22","doi-asserted-by":"crossref","first-page":"4577","DOI":"10.3390\/molecules29194577","article-title":"Biochemical modulators of tight junctions (TJs): Occludin, Claudin-2 and Zonulin as biomarkers of intestinal barrier leakage in the diagnosis and assessment of inflammatory bowel disease progression","volume":"29","author":"G\u00f3recka","year":"2024","journal-title":"Molecules"},{"key":"2025121401064432400_jjaf200-B23","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1111\/den.14672","article-title":"Present and future of endoscopy precision for inflammatory bowel disease","volume":"36","author":"Santacroce","year":"2024","journal-title":"Dig Endosc"},{"key":"2025121401064432400_jjaf200-B24","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1053\/j.gastro.2025.03.005","article-title":"Artificial intelligence\u2013driven personalized medicine: transforming clinical practice in inflammatory bowel disease","volume":"169","author":"Iacucci","year":"2025","journal-title":"Gastroenterology"},{"key":"2025121401064432400_jjaf200-B25","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/s41575-025-01063-x","article-title":"Shaping the future of inflammatory bowel disease: a global research agenda for better management and public health response","volume":"22","author":"Solitano","year":"2025","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"2025121401064432400_jjaf200-B26","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1093\/ibd\/izab059","article-title":"Ultra-high magnification endocytoscopy and molecular markers for defining endoscopic and histologic remission in ulcerative colitis\u2014an exploratory study to define deep remission","volume":"27","author":"Iacucci","year":"2021","journal-title":"Inflamm Bowel Dis"},{"key":"2025121401064432400_jjaf200-B27","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1136\/gutjnl-2011-300695","article-title":"Local barrier dysfunction identified by confocal laser endomicroscopy predicts relapse in inflammatory bowel disease","volume":"61","author":"Kiesslich","year":"2012","journal-title":"Gut"},{"key":"2025121401064432400_jjaf200-B28","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1109\/CVPR.2016.90","volume-title":"2016 IEEE Conference on Computer Vision and Pattern Recognition (CVPR).","author":"He","year":"2016"},{"key":"2025121401064432400_jjaf200-B29","doi-asserted-by":"crossref","first-page":"103298","DOI":"10.1016\/j.media.2024.103298","article-title":"Foundation models in gastrointestinal endoscopic AI: Impact of architecture, pre-training approach and data efficiency","volume":"98","author":"Boers","year":"2024","journal-title":"Med Image Anal"},{"key":"2025121401064432400_jjaf200-B30","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1093\/ibd\/izac233","article-title":"Computer-aided imaging analysis of probe-based confocal laser endomicroscopy with molecular labeling and gene expression identifies markers of response to biological therapy in IBD Patients: the endo-omics study","volume":"29","author":"Iacucci","year":"2023","journal-title":"Inflamm Bowel Dis"},{"key":"2025121401064432400_jjaf200-B31","doi-asserted-by":"crossref","first-page":"2980","DOI":"10.1109\/ICCV.2017.322","volume-title":"2017 IEEE International Conference on Computer Vision (ICCV).","author":"He","year":"2017"}],"container-title":["Journal of Crohn's and Colitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/advance-article-pdf\/doi\/10.1093\/ecco-jcc\/jjaf200\/65397097\/jjaf200.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/19\/11\/jjaf200\/65397097\/jjaf200.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article-pdf\/19\/11\/jjaf200\/65397097\/jjaf200.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T06:06:52Z","timestamp":1765692412000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ecco-jcc\/article\/doi\/10.1093\/ecco-jcc\/jjaf200\/8328302"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11]]},"references-count":31,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2025,12,5]]}},"URL":"https:\/\/doi.org\/10.1093\/ecco-jcc\/jjaf200","relation":{},"ISSN":["1873-9946","1876-4479"],"issn-type":[{"value":"1873-9946","type":"print"},{"value":"1876-4479","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,11]]},"published":{"date-parts":[[2025,11]]},"article-number":"jjaf200"}}