{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T13:05:20Z","timestamp":1782824720017,"version":"3.54.5"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T00:00:00Z","timestamp":1769472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-178090"],"award-info":[{"award-number":["PJT-178090"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MT2-168050"],"award-info":[{"award-number":["MT2-168050"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007658","name":"Crohn\u2019s and Colitis Canada","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007658","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100019889","name":"Weston Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019889","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canadian National Organoid Network"},{"DOI":"10.13039\/501100000024","name":"CIHR","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Canadian Graduate Scholarship"},{"name":"UBC Four Year Doctoral"},{"DOI":"10.13039\/100012285","name":"BC Children\u2019s Hospital Research Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012285","id-type":"DOI","asserted-by":"crossref"}]},{"name":"British Columbia Graduate Scholarship"},{"DOI":"10.13039\/501100022437","name":"Children with Intestinal and Liver Disorders","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100022437","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Foundation Chair in Pediatric Gastroenterology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The inflammatory bowel disease (IBD) ulcerative colitis (UC) is characterized by colonic mucosal inflammation and barrier dysfunction. We hypothesized that UC causes persistent defects in mucosal homeostasis, evident even in the absence of active inflammation, contributing to disease chronicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To test our hypothesis, we grew patient biopsy-derived sigmoid colonoids into air-liquid interface (ALI) monolayers, characterizing them through microscopy, proteomics, bulk RNA Sequencing (RNAseq), and their susceptibility to UC patient-isolated Escherichia coli pathobiont p19A.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Non-IBD ALI monolayers formed uniform crypt-like structures and a thick mucus layer containing all epithelial-derived proteins previously identified in human colonic mucus. In contrast, ALI monolayers from UC patients displayed a range of impairments, with classification ranging from a mild phenotype with distorted architecture and a thinner, more permeable mucus layer to a severe phenotype with defects in cellular differentiation and an inability to produce a mucus layer. With the use of transcriptome analysis, we identified activated pathways associated with extracellular matrix formation and cell signaling, including numerous cancer-associated genes in UC ALI monolayers, which also proved significantly more susceptible to E. coli p19A.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Taken together, the culturing of patient biopsies into ALI colonoid monolayers provides a powerful model to assess human colonic mucosal development, healing, homeostasis, and mucus barrier function, revealing that UC-derived colonoid monolayers display a range of developmental and functional defects that persist in the absence of inflammation.<\/jats:p>\n                  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BC,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of British Columbia , Vancouver, BC,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois-Michel","family":"Boisvert","sequence":"additional","affiliation":[{"name":"Department of Immunology and Cell Biology, Universit\u00e9 de Sherbrooke , Sherbrooke, Qu\u00e9bec,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4740-8209","authenticated-orcid":false,"given":"Brian","family":"Bressler","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, University of British Columbia , Vancouver, BC,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1345-6747","authenticated-orcid":false,"given":"Bruce A","family":"Vallance","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of British Columbia , Vancouver, BC,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,1,27]]},"reference":[{"key":"2026030209521325600_izaf318-B1","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/S0140-6736(23)00966-2","article-title":"Ulcerative colitis","volume":"402","author":"Berre","year":"2023","journal-title":"Lancet"},{"key":"2026030209521325600_izaf318-B2","doi-asserted-by":"crossref","first-page":"17562848231159452","DOI":"10.1177\/17562848231159452","article-title":"Is there an optimal sequence of biologic therapies for inflammatory bowel 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