{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T08:52:08Z","timestamp":1782377528635,"version":"3.54.5"},"reference-count":18,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["20R76508"],"award-info":[{"award-number":["20R76508"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Point of Care Diagnostics in Human Health","award":["20R75988"],"award-info":[{"award-number":["20R75988"]}]},{"name":"Broad Medical Research Program","award":["IBD-0326"],"award-info":[{"award-number":["IBD-0326"]}]},{"DOI":"10.13039\/100001063","name":"Crohn\u2019s & Colitis Foundation of America","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100001063","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background &amp; Aims<\/jats:title>\n                  <jats:p>Clostridioides difficile is a toxin-secreting bacteria that is an urgent antimicrobial resistance threat, with approximately 25% of patients developing recurrent infections. Inflammatory bowel disease (IBD) patients are at increased risk of severe, recurrent C. difficile infection.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>To investigate a role for C. difficile infection in IBD pathogenesis, we collected peripheral blood and stool from 20 each of ulcerative colitis patients, Crohn\u2019s disease patients, and healthy control subjects. We used a flow cytometric activation induced marker assay to quantify C. difficile toxin\u2013specific CD4+ T cells and 16S ribosomal RNA sequencing to study microbiome diversity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We found IBD patients had significantly increased levels of C. difficile toxin B\u2013specific CD4+ T cells, but not immunoglobulin G or immunoglobulin A, compared with healthy control subjects. Within antigen-specific CD4+ T cells, T helper type 17 cells and cells expressing the gut homing receptor integrin \u03b27 were reduced compared with healthy control subjects, similar to our previous study of non-IBD patients with recurrent C. difficile infection. Stool microbiome analysis revealed that gut homing, toxin-specific CD4+ T cells negatively associated with microbial diversity and, along with T helper type 17 cells, positively associated with bacteria enriched in healthy control subjects.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These data suggest that IBD patients, potentially due to underlying intestinal dysbiosis, experience undiagnosed C. difficile infections that result in impaired toxin-specific immunity. This may contribute to the development of inflammatory T cell responses toward commensal bacteria and provide a rationale for C. difficile testing in IBD patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ibd\/izad238","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T19:40:59Z","timestamp":1698176459000},"page":"820-828","source":"Crossref","is-referenced-by-count":7,"title":["Dysregulated Immunity to <i>Clostridioides difficile<\/i> in IBD Patients Without a History of Recognized Infection"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3153-2045","authenticated-orcid":false,"given":"Laura","family":"Cook","sequence":"first","affiliation":[{"name":"Department of Medicine, University of British Columbia , Vancouver, BC , Canada"},{"name":"BC Children\u2019s Hospital Research Institute , Vancouver, BC , Canada"},{"name":"Department of Microbiology and Immunology, University of Melbourne at The Peter Doherty Institute for Infection and Immunity , Melbourne, VIC , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May Q","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of British Columbia , Vancouver, BC , Canada"},{"name":"BC Children\u2019s Hospital Research Institute , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D","family":"Rees","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of British Columbia , Vancouver, BC , Canada"},{"name":"BC Children\u2019s Hospital Research Institute , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alana","family":"Schick","sequence":"additional","affiliation":[{"name":"Gut4Health, BC Children\u2019s Hospital Research Institute , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J","family":"Lisko","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of British Columbia , Vancouver, BC , Canada"},{"name":"BC Children\u2019s Hospital Research Institute , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genelle R","family":"Lunken","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of British Columbia , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojiao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of British Columbia , Vancouver, BC , Canada"},{"name":"BC Children\u2019s Hospital Research Institute , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of British Columbia , Vancouver, BC , 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K","family":"Levings","sequence":"additional","affiliation":[{"name":"BC Children\u2019s Hospital Research Institute , Vancouver, BC , Canada"},{"name":"Department of Surgery, University of British Columbia , Vancouver, BC , Canada"},{"name":"School of Biomedical Engineering, University of British Columbia , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore S","family":"Steiner","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of British Columbia , Vancouver, BC , Canada"},{"name":"BC Children\u2019s Hospital Research Institute , Vancouver, BC , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"issue":"9","key":"2024050205521712400_CIT0001","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1056\/NEJMoa1408913","article-title":"Burden of Clostridium difficile infection in the United 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