{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:17:05Z","timestamp":1785428225610,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,13]]},"group-title":"Immunology","reference-count":31,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"funder":[{"name":"Gastrointestinal Research Foundation"},{"award":["Microbiome Junior Investigator Research Award"],"award-info":[{"award-number":["Microbiome Junior Investigator Research Award"]}],"id":[{"id":"https:\/\/ror.org\/00y65x556","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008590","name":"Falk Medical Research Trust","doi-asserted-by":"crossref","award":["Catalyst Award"],"award-info":[{"award-number":["Catalyst Award"]}],"id":[{"id":"10.13039\/100008590","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100008590","name":"Falk Medical Research Trust","doi-asserted-by":"crossref","award":["Transformational Award"],"award-info":[{"award-number":["Transformational Award"]}],"id":[{"id":"10.13039\/100008590","id-type":"DOI","asserted-by":"crossref"}]},{"award":["Research Accelerator"],"award-info":[{"award-number":["Research Accelerator"]}],"id":[{"id":"https:\/\/ror.org\/03xjacd83","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Caregiver Catalyst"],"award-info":[{"award-number":["Caregiver Catalyst"]}],"id":[{"id":"https:\/\/ror.org\/03xjacd83","id-type":"ROR","asserted-by":"publisher"}]},{"award":["Innovations Pitch Competition"],"award-info":[{"award-number":["Innovations Pitch Competition"]}],"id":[{"id":"https:\/\/ror.org\/03xjacd83","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["P30-DK097948"],"award-info":[{"award-number":["P30-DK097948"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["1K08DK1114713"],"award-info":[{"award-number":["1K08DK1114713"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL178625"],"award-info":[{"award-number":["R01HL178625"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Intestinal barrier failure is a key characteristic of both kinds of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn\u2019s disease (CD). The intestinal barrier, or gut mucosal barrier, is composed of mucus and a tightly interconnected single layer of intestinal epithelial cells (IEC) that line the gut. Together, these components work to contain the gut microbiota within the gut lumen and when they fail, microbes, microbial products, or microbial components cause damage, inflammation, and immune activation in host tissue. We previously reported that High mobility group box 1 (HMGB1) in colonic mucus aggregates bacteria, limits bacterial invasion through mucus, and prevents bacteria from adhering to host tissue. Epithelial surface-associated HMGB1 is decreased in active UC lesions and low levels of HMGB1 are associated with high levels of tissue-adherent bacteria expressing adhesins carrying the molecular target of HMGB1 (ToH1). The study reported here was designed to determine whether HMGB1 defense is also compromised in active lesions from CD patients.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Immunofluorescence microscopy was used to visualize mucus and HMGB1 in tissue from colonic resections performed in CD and non-IBD control patients.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Active CD lesions had areas where the IEC were absent or pulling away from underlying tissue along with areas of increased mucus thickness and goblet cells full of mucus highly positive for alpha-linked-fucose residues. The surface associated HMGB1 was also decreased in active CD lesions.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Tissue from CD patients exhibited cellular and acellular intestinal barrier defects in comparison to control patients. We observed the previously reported loss of IEC barrier integrity and abnormalities in the amount and distribution of mucus in CD lesions. We also report for the first time that CD is associated with decreased HMGB1 defense at the colon surface.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.09.737505","type":"posted-content","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:55:23Z","timestamp":1784008523000},"source":"Crossref","is-referenced-by-count":0,"title":["A preliminary study of HMGB1 defense in Crohn\u2019s disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6701-1640","authenticated-orcid":false,"given":"Anne-Marie C.","family":"Overstreet","sequence":"first","affiliation":[{"name":"Department of Microbial Sciences in Health, Cleveland Clinic Research, Cleveland Clinic, Cleveland, Ohio, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylee A.","family":"Hunterx","sequence":"additional","affiliation":[{"name":"Department of Microbial Sciences in Health, Cleveland Clinic Research, Cleveland Clinic, Cleveland, Ohio, United States of America"},{"name":"Department of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivani","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Microbial Sciences in Health, Cleveland Clinic Research, Cleveland Clinic, Cleveland, Ohio, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hridai","family":"Dharan","sequence":"additional","affiliation":[{"name":"Department of Microbial Sciences in Health, Cleveland Clinic Research, Cleveland Clinic, Cleveland, Ohio, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Overend","sequence":"additional","affiliation":[{"name":"Department of Microbial Sciences in Health, Cleveland Clinic Research, Cleveland Clinic, Cleveland, Ohio, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5072-3835","authenticated-orcid":false,"given":"Jeannette S.","family":"Messer","sequence":"additional","affiliation":[{"name":"Department of Microbial Sciences in Health, Cleveland Clinic Research, Cleveland Clinic, Cleveland, Ohio, United States of America"},{"name":"Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America"},{"name":"Cleveland Clinic Center for Microbiome and Human Health, Cleveland Clinic Research, Cleveland, Ohio, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026071603101122000_2026.07.09.737505v1.1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i5.1165"},{"key":"2026071603101122000_2026.07.09.737505v1.2","doi-asserted-by":"publisher","DOI":"10.1080\/17474124.2017.1343143"},{"key":"2026071603101122000_2026.07.09.737505v1.3","doi-asserted-by":"crossref","first-page":"856962","DOI":"10.3389\/fcimb.2022.856962","article-title":"Mucus and Mucins: The Underappreciated Host Defence System","volume":"12","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"2026071603101122000_2026.07.09.737505v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.169"},{"key":"2026071603101122000_2026.07.09.737505v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2011.09.006"},{"issue":"6","key":"2026071603101122000_2026.07.09.737505v1.6","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S2468-1253(24)00390-X","article-title":"The intestinal barrier: a pivotal role in health, inflammation, and cancer","volume":"10","year":"2025","journal-title":"The Lancet Gastroenterology & Hepatology"},{"key":"2026071603101122000_2026.07.09.737505v1.7","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13117"},{"issue":"1","key":"2026071603101122000_2026.07.09.737505v1.8","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1186\/s13054-025-05309-7","article-title":"A review of gut failure as a cause and consequence of critical illness","volume":"29","year":"2025","journal-title":"Crit Care"},{"key":"2026071603101122000_2026.07.09.737505v1.9","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.10.014"},{"key":"2026071603101122000_2026.07.09.737505v1.10","doi-asserted-by":"crossref","unstructured":"Orlemann, T. , et al., Intestinal barrier healing is superior to transmural healing to prevent disease progression in clinical remittent patients with inflammatory bowel disease. 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