{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T19:58:49Z","timestamp":1769975929758,"version":"3.49.0"},"reference-count":34,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The worldwide prevalence of autoimmune diseases that have limited treatment options and preventive strategies is rapidly rising. There is growing evidence that the microbiota and the integrity of the intestinal barrier play a role in autoimmune diseases. The potential to evaluate intestinal barrier integrity for susceptible individuals and to determine whether restoring intestinal junction integrity impacts autoimmune diseases is an important area of research that requires further attention. In the intestinal permeability model of autoimmune diseases, the breakdown of the intestinal tight junction proteins (zonulin\/occludin) allows bacteria, toxins, undigested dietary proteins, and other antigens to pass into the lumen, thereby increasing the number of inflammatory reactions and the activation of immune cells throughout the body. In this study, we investigate the relationship between zonulin\/occludin antibodies, which are used to determine intestinal permeability, with autoantibodies used to diagnose autoimmunity. Our investigation may identify significant levels of circulating autoantibodies in human subjects with intestinal permeability compared to those without intestinal permeability. Furthermore, we identified that significant positive linear correlations between serum occludin\/zonulin antibodies and circulating autoantibodies could be used to determine autoimmune diseases.<\/jats:p>","DOI":"10.3390\/ijms242216352","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T10:51:37Z","timestamp":1700045497000},"page":"16352","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Relationships between Intestinal Permeability and Target Antibodies for a Spectrum of Autoimmune Diseases"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7985-476X","authenticated-orcid":false,"given":"Datis","family":"Kharrazian","sequence":"first","affiliation":[{"name":"Harvard Medical School, Boston, MA 02215, USA"},{"name":"Massachusetts General Hospital, Charlestown, MA 02114, USA"},{"name":"Department of Preventive Medicine, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha","family":"Herbert","sequence":"additional","affiliation":[{"name":"Harvard Medical School, Boston, MA 02215, USA"},{"name":"Massachusetts General Hospital, Charlestown, MA 02114, USA"},{"name":"Higher Synthesis Foundation, Cambridge, MA 02138, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4259-7752","authenticated-orcid":false,"given":"Jama","family":"Lambert","sequence":"additional","affiliation":[{"name":"Independent Researcher, Puerto Vallarta 48300, Jalisco, Mexico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.12691\/ijcd-3-4-8","article-title":"The world incidence and prevalence of autoimmune disease is increasing","volume":"3","author":"Lerner","year":"2015","journal-title":"Int. J. Celiac Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"598","DOI":"10.3389\/fimmu.2017.00598","article-title":"Leaky gut as a danger signal for autoimmune diseases","volume":"23","author":"Mu","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41577-022-00727-y","article-title":"The impact of the gut microbiome on extra-intestinal autoimmune diseases","volume":"23","author":"Miyauchi","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/ncpgasthep0259","article-title":"Mechanisms of disease: The role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases","volume":"2","author":"Fasano","year":"2005","journal-title":"Nat. Clin. Pract. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Charoensappakit, A., Sae-Khow, K., and Leelahavanichkul, A. (2022). gut barrier damage and gut translocation of pathogen molecules in lupus, an impact of innate immunity (macrophages and neutrophils) in autoimmune disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158223"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/s12016-011-8291-x","article-title":"Leaky gut and autoimmune diseases","volume":"42","author":"Fasano","year":"2012","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Paray, B.A., Albeshr, M.F., Jan, A.T., and Rather, I.A. (2020). Leaky gut and autoimmunity: An intricate balance in individuals health and the diseased state. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249770"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1749-6632.2012.06538.x","article-title":"Zonulin, regulation of tight junctions, and autoimmune diseases","volume":"1258","author":"Fasano","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.2174\/1568026618666181115100610","article-title":"Recognizing the leaky gut as a trans-diagnostic target for neuroimmune disorders using clinical chemistry and molecular immunology assays","volume":"18","author":"Simeonova","year":"2018","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5669","DOI":"10.3748\/wjg.v23.i31.5669","article-title":"Fluctuation of zonulin levels in blood vs stability of antibodies","volume":"23","author":"Vojdani","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1593\/tlo.09115","article-title":"Expression of Zonulin, c-kit, and glial fibrillary acidic protein in human gliomas","volume":"2","author":"Skardelly","year":"2009","journal-title":"Transl. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"D\u00edaz-Cor\u00e1nguez, M., Segovia, J., L\u00f3pez-Ornelas, A., Puerta-Guardo, H., Ludert, J., Ch\u00e1vez, B., Meraz-Cruz, N., and Gonz\u00e1lez-Mariscal, L. (2013). Transmigration of neural stem cells across the blood brain barrier induced by glioma cells. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0060655"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1251384","DOI":"10.1080\/21688370.2016.1251384","article-title":"Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases","volume":"4","author":"Sturgeon","year":"2016","journal-title":"Tissue Barriers"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1007\/s13311-017-0582-3","article-title":"Intestinal permeability in relapsing-remitting multiple sclerosis","volume":"15","author":"Buscarinu","year":"2018","journal-title":"Neurotherapeutics"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Nouri, M., Bredberg, A., Westr\u00f6m, B., and Lavasani, S. (2014). Intestinal barrier dysfunction develops at the onset of experimental autoimmune encephalomyelitis, and can be induced by adoptive transfer of auto-reactive T cells. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0106335"},{"key":"ref_16","first-page":"1500","article-title":"Fecal microbiota in early rheumatoid arthritis","volume":"35","author":"Vaahtovuo","year":"2008","journal-title":"J. Rheumatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.3899\/jrheum.170791","article-title":"Is gut microbial LPS a potential trigger of juvenile idiopathic arthritis?","volume":"44","author":"Azzouz","year":"2017","journal-title":"J. Rheumatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4244","DOI":"10.1016\/j.febslet.2014.05.034","article-title":"Arthritis susceptibility and the gut microbiome","volume":"588","author":"Taneja","year":"2014","journal-title":"FEBS Lett."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Picchianti-Diamanti, A., Rosado, M.M., and D\u2019Amelio, R. (2018). Infectious agents and inflammation: The role of microbiota in autoimmune arthritis. Front. Microbiol., 8.","DOI":"10.3389\/fmicb.2017.02696"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1136\/annrheumdis-2018-212942","article-title":"How the gut inflames the joints","volume":"77","author":"Pisetsky","year":"2018","journal-title":"Ann. Rheum. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1002\/jbmr.2887","article-title":"Links between the microbiome and bone","volume":"31","author":"Hernandez","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1080\/10408398.2015.1010034","article-title":"Gut microbiota-bone axis","volume":"57","author":"Villa","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1097\/00005176-199903000-00010","article-title":"Altered intestinal permeability to mannitol in diabetes mellitus type I","volume":"28","author":"Secondulfo","year":"1999","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1080\/0891693021000008526","article-title":"Intestinal permeability to mannitol and lactulose in children with type 1 diabetes with the HLA-DQB1*02 allele","volume":"35","author":"Kuitunen","year":"2002","journal-title":"Autoimmunity"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.2337\/db05-1593","article-title":"Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives","volume":"55","author":"Sapone","year":"2006","journal-title":"Diabetes"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.dld.2003.09.016","article-title":"Ultrastructural mucosal alterations and increased intestinal permeability in non-celiac, type I diabetic patients","volume":"36","author":"Secondulfo","year":"2004","journal-title":"Dig. Liver Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1007\/s12016-008-8088-8","article-title":"Atypical p-ANCA in PSC and AIH: A hint toward a \u201cleaky gut\u201d?","volume":"36","author":"Terjung","year":"2009","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_28","first-page":"5153","article-title":"Abnormal intestinal permeability and microbiota in patients with autoimmune hepatitis","volume":"8","author":"Lin","year":"2015","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kobayashi, T., Iwaki, M., Nakajima, A., Nogami, A., and Yoneda, M. (2022). Current research on the pathogenesis of NAFLD\/NASH and the gut-liver axis: Gut microbiota, dysbiosis, and leaky-gut syndrome. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911689"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cell.2020.03.007","article-title":"Challenges, progress, and prospects of developing therapies to treat autoimmune diseases","volume":"181","author":"Fugger","year":"2020","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"673708","DOI":"10.3389\/fimmu.2021.673708","article-title":"Partners in leaky gut syndrome: Intestinal dysbiosis and autoimmunity","volume":"12","author":"Kinashi","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.tem.2022.01.002","article-title":"Gut barrier disruption and chronic disease","volume":"33","author":"Martel","year":"2022","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1136\/gutjnl-2021-325428","article-title":"What to do about the leaky gut","volume":"71","author":"Camilleri","year":"2022","journal-title":"Gut"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"946248","DOI":"10.3389\/fimmu.2022.946248","article-title":"Gut microbiota, leaky gut, and autoimmune diseases","volume":"13","author":"Christovich","year":"2022","journal-title":"Front. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/22\/16352\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:23:27Z","timestamp":1760131407000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/22\/16352"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,15]]},"references-count":34,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["ijms242216352"],"URL":"https:\/\/doi.org\/10.3390\/ijms242216352","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,15]]}}}