{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T05:02:56Z","timestamp":1779771776900,"version":"3.53.1"},"reference-count":52,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,24]],"date-time":"2026-05-24T00:00:00Z","timestamp":1779580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Objectives: To evaluate serum zonulin and CHI3L1 as indicators of intestinal permeability and disease activity in pediatric celiac disease and to explore their associations with histopathological findings and nutritional status. Methods: This prospective cross-sectional study included 131 pediatric patients with CD (aged 2\u201318 years) and 42 healthy controls. Patients were classified as newly diagnosed, gluten-free diet (GFD)-adherent, or GFD-nonadherent. Body mass index was calculated, and serum levels of micronutrients, zonulin, and CHI3L1 were measured using a sandwich enzyme-linked immunosorbent assay. Associations with histopathological findings, serological markers, and nutritional parameters were analyzed. Results: Age and sex distributions were similar across groups (mean age: 10.9 \u00b1 4.27 years). Serum zonulin and CHI3L1 levels were moderately positively correlated (r = 0.525, p &lt; 0.001). Both biomarkers showed significant positive correlations with Marsh scores and tissue transglutaminase IgA levels. Zonulin was inversely correlated with hemoglobin, serum iron, and ferritin, whereas CHI3L1 showed negative correlations with hemoglobin and folate. Parathyroid hormone levels were positively correlated with both biomarkers. Receiver operating characteristic analysis demonstrated acceptable discriminatory performance for distinguishing CD from controls (AUC: 0.713 for zonulin and 0.709 for CHI3L1). Conclusions: Serum zonulin and CHI3L1 levels are associated with disease activity and mucosal injury in pediatric CD but do not directly reflect micronutrient status. These biomarkers may complement conventional monitoring parameters by providing additional information on intestinal permeability and inflammatory activity during follow-up.<\/jats:p>","DOI":"10.3390\/children13060730","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T02:32:28Z","timestamp":1779676348000},"page":"730","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Serum Zonulin and Chitinase (CHI3L1) as Biomarkers of Intestinal Permeability and Disease Activity in Pediatric Celiac Disease"],"prefix":"10.3390","volume":"13","author":[{"given":"Ay\u015feg\u00fcl Cebe","family":"Tok","sequence":"first","affiliation":[{"name":"Department of Pediatric Gastroenterology, Etlik City Hospital, University of Health Sciences, Ankara 06010, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0879-9091","authenticated-orcid":false,"given":"Oya","family":"Say\u0131n","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Techniques, Vocational School of Health Services, Dokuz Eylul University, Izmir 35340, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Caio, G., Volta, U., Sapone, A., Leffler, D.A., De Giorgio, R., and Catassi, C. (2019). Celiac disease: A comprehensive current review. BMC Med., 17.","DOI":"10.1186\/s12916-019-1380-z"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1053\/j.gastro.2024.02.050","article-title":"How Future Pharmacologic Therapies for Celiac Disease Will Complement the Gluten-Free Diet","volume":"167","author":"Discepolo","year":"2024","journal-title":"Gastroenterology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1053\/j.gastro.2008.03.023","article-title":"Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3","volume":"135","author":"Lammers","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Binienda, A., Twardowska, A., Makaro, A., and Salaga, M. (2020). Dietary carbohydrates and lipids in the pathogenesis of leaky gut syndrome: An overview. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21218368"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1016\/S0140-6736(00)02169-3","article-title":"Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease","volume":"355","author":"Fasano","year":"2000","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e2023063050","DOI":"10.1542\/peds.2023-063050","article-title":"CD-GEMM Study Group et al. Zonulin as a Biomarker for the Development of Celiac Disease","volume":"153","author":"DaFonte","year":"2024","journal-title":"Pediatrics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1007\/s00011-020-01371-9","article-title":"The expression levels of CHI3L1 and IL15R\u03b1 correlate with TGM2 in duodenum biopsies of patients with celiac disease","volume":"69","author":"Catrogiovanni","year":"2020","journal-title":"Inflamm. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1007\/s10753-012-9569-8","article-title":"Evaluation of CHI3L-1 and CHIT-1 expression in differentiated and polarized macrophages","volume":"36","author":"Malaguarnera","year":"2013","journal-title":"Inflammation"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.imbio.2015.09.023","article-title":"CHI3L1 nuclear localization in monocyte derived dendritic cells","volume":"221","author":"Tibullo","year":"2016","journal-title":"Immunobiology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.bone.2014.01.005","article-title":"Determination of CHI3L1s family during osteoclastogenesis","volume":"61","author":"Tibullo","year":"2014","journal-title":"Bone"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1159\/000444855","article-title":"CHI3L1 3 Like-1: An Emerging Molecule Involved in Diabetes and Diabetic Complications","volume":"83","author":"Malaguarnera","year":"2016","journal-title":"Pathobiology"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mandile, R., Maglio, M., Mosca, C., Marano, A., Discepolo, V., Troncone, R., and Auricchio, R. (2022). Mucosal Healing in Celiac Disease: Villous Architecture and Immunohistochemical Features in Children on a Long-Term Gluten Free Diet. Nutrients, 14.","DOI":"10.3390\/nu14183696"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/nm.2656","article-title":"High abundance of plasma cells secreting transglutaminase 2-specific IgA autoantibodies with limited somatic hypermutation in celiac disease intestinal lesions","volume":"18","author":"Mesin","year":"2012","journal-title":"Nat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1111\/cei.12366","article-title":"Intestinal titres of anti-tissue transglutaminase 2 antibodies correlate positively with mucosal damage degree and inversely with gluten-free diet duration in coeliac disease","volume":"177","author":"Tosco","year":"2014","journal-title":"Clin. Exp. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.14309\/ajg.0000000000003400","article-title":"Assessing Mucosal Recovery During the First 15 Months of Adopting a Gluten-Free Diet in Children with Celiac Disease","volume":"120","author":"Chang","year":"2025","journal-title":"Am. J. Gastroenterol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Leonard, M.M., Cureton, P., and Fasano, A. (2017). Indications and Use of the Gluten Contamination Elimination Diet for Patients with Non-Responsive Celiac Disease. Nutrients, 9.","DOI":"10.3390\/nu9101129"},{"key":"ref_17","first-page":"101","article-title":"The value of a biopsy in celiac disease follow up: Assessment of the small bowel after 6 and 24 months treatment with a gluten free diet","volume":"112","author":"Sadeghi","year":"2020","journal-title":"Rev. Esp. Enferm. Dig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.clnesp.2023.01.031","article-title":"Nutritional assessment of women with celiac disease compared to the general population","volume":"54","author":"Fossli","year":"2023","journal-title":"Clin. Nutr. ESPEN"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"28315","DOI":"10.1038\/s41598-025-12631-1","article-title":"Vitamin and trace elements imbalance are very common in adult patients with newly diagnosed Celiac disease","volume":"15","author":"Nuermaimaiti","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1080\/00365520500235334","article-title":"Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines","volume":"41","author":"Drago","year":"2006","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1152\/physrev.00003.2008","article-title":"Zonulin and its regulation of intestinal barrier function: The biological door to inflammation, autoimmunity, and cancer","volume":"91","author":"Fasano","year":"2011","journal-title":"Physiol. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1016\/j.cgh.2012.08.012","article-title":"Intestinal permeability and its regulation by zonulin: Diagnostic and therapeutic implications","volume":"10","author":"Fasano","year":"2012","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mart\u00ednez Gallego, M.\u00c1., Crespo S\u00e1nchez, M.G., Serrano Olmedo, M.G., Soto, A.B., Casasempere, S.\u00c1., Nozal, P., Mart\u00ednez-Ojinaga, E., Arias, M.M., Losantos-Garc\u00eda, I., and Molero-Luis, M. (2024). Trends in Faecal Zonulin Concentrations in Paediatric Patients with Celiac Disease at Baseline and on a Gluten-Free Diet: Exploring Correlations with Other Faecal Biomarkers. Nutrients, 16.","DOI":"10.3390\/nu16050684"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nature12721","article-title":"Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells","volume":"504","author":"Furusawa","year":"2013","journal-title":"Nature"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nature12726","article-title":"Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation","volume":"504","author":"Arpaia","year":"2013","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1084\/jem.20081271","article-title":"Role of breast regression protein 39 (BRP-39)\/CHI3L1 3-like-1 in Th2 and IL-13-induced tissue responses and apoptosis","volume":"206","author":"Lee","year":"2009","journal-title":"J. Exp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1146\/annurev-physiol-012110-142250","article-title":"Role of chitin and CHI3L1\/CHI3L1-like proteins in inflammation, tissue remodeling, and injury","volume":"73","author":"Lee","year":"2011","journal-title":"Annu. Rev. Physiol."},{"key":"ref_28","first-page":"010502","article-title":"YKL-40 as a biomarker in various inflammatory diseases: A review","volume":"34","author":"Blazevic","year":"2024","journal-title":"Biochem. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Monzani, A., Marcolin, S., Medina, F., Valentino, K., and Rabbone, I. (2024). BMI Status of Children with Celiac Disease Has Changed in the Last Decades: A 30-Year Retrospective Study. Nutrients, 16.","DOI":"10.20944\/preprints202407.2150.v1"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Montoro-Huguet, M.A., Santolaria-Piedrafita, S., Ca\u00f1amares-Orbis, P., and Garc\u00eda-Erce, J.A. (2021). Iron Deficiency in Celiac Disease: Prevalence, Health Impact, and Clinical Management. Nutrients, 13.","DOI":"10.3390\/nu13103437"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Talarico, V., Giancotti, L., Mazza, G.A., Miniero, R., and Bertini, M. (2021). Iron Deficiency Anemia in Celiac Disease. Nutrients, 13.","DOI":"10.3390\/nu13051695"},{"key":"ref_32","first-page":"1","article-title":"Iron deficiency anemia in newly diagnosed celiac disease in children","volume":"68","author":"Sanseviero","year":"2016","journal-title":"Minerva Pediatr."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Stefanelli, G., Viscido, A., Longo, S., Magistroni, M., and Latella, G. (2020). Persistent Iron Deficiency Anemia in Patients with Celiac Disease Despite a Gluten-Free Diet. Nutrients, 12.","DOI":"10.3390\/nu12082176"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4705","DOI":"10.1007\/s00431-024-05721-1","article-title":"Iron deficiency without anemia in children with newly diagnosed celiac disease: 1-year follow-up of ferritin levels, with and without iron supplementation","volume":"183","author":"Trotskovsky","year":"2024","journal-title":"Eur. J. Pediatr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2784","DOI":"10.1016\/j.clnu.2021.03.006","article-title":"Micronutrient deficiencies in children with coeliac disease; a double-edged sword of both untreated disease and treatment with gluten-free diet","volume":"40","author":"McGrogan","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3975","DOI":"10.3390\/nu5103975","article-title":"Vitamin and mineral deficiencies are highly prevalent in newly diagnosed celiac disease patients","volume":"5","author":"Wierdsma","year":"2013","journal-title":"Nutrients"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Szaflarska-Pop\u0142awska, A., Doli\u0144ska, A., and Ku\u015bmierek, M. (2022). Nutritional Imbalances in Polish Children with Coeliac Disease on a Strict Gluten-Free Diet. Nutrients, 14.","DOI":"10.3390\/nu14193969"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/j.clnu.2023.05.003","article-title":"Nutrient deficiencies in children with celiac disease during long term follow-up","volume":"42","author":"Kreutz","year":"2023","journal-title":"Clin. Nutr."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"617","DOI":"10.3349\/ymj.2009.50.5.617","article-title":"Celiac disease: Presentation of 109 children","volume":"50","author":"Kuloglu","year":"2009","journal-title":"Yonsei Med. J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"215","DOI":"10.5152\/tjg.2018.17451","article-title":"Bone mineral density and vitamin K status in children with celiac disease: Is there a relation?","volume":"29","author":"Volkan","year":"2018","journal-title":"Turk. J. Gastroenterol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Infantino, C., Francavilla, R., Vella, A., Cenni, S., Principi, N., Strisciuglio, C., and Esposito, S. (2022). Role of Vitamin D in Celiac Disease and Inflammatory Bowel Diseases. Nutrients, 14.","DOI":"10.3390\/nu14235154"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1016\/j.dld.2004.05.010","article-title":"Coeliac disease in Middle Eastern countries: A challenge for the evolutionary history of this complex disorder?","volume":"36","author":"Rostami","year":"2004","journal-title":"Dig. Liver Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1097\/MPG.0000000000002417","article-title":"Should We Assess Vitamin D Status in Pediatric Patients with Celiac Disease?","volume":"69","author":"Ahlawat","year":"2019","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1515\/jpem-2012-0048","article-title":"Is vitamin D deficiency a feature of pediatric celiac disease?","volume":"25","author":"Villanueva","year":"2012","journal-title":"J. Pediatr. Endocrinol. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1007\/s12016-010-8237-8","article-title":"The clinical significance of 25OH-Vitamin D status in celiac disease","volume":"42","author":"Lerner","year":"2012","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.jpeds.2020.08.089","article-title":"Lower Level of Plasma 25-Hydroxyvitamin D in Children at Diagnosis of Celiac Disease Compared with Healthy Subjects: A Case-Control Study","volume":"228","author":"Lionetti","year":"2021","journal-title":"J. Pediatr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"181","DOI":"10.4274\/jcrpe.galenos.2018.2018.0272","article-title":"Vitamin D Deficiency and Insufficiency According to the Current Criteria for Children: Vitamin D Status of Elementary School Children in Turkey","volume":"11","year":"2019","journal-title":"J. Clin. Res. Pediatr. Endocrinol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1080\/003655200750024146","article-title":"Three years\u2019 follow-up of bone density in adult coeliac disease: Significance of secondary hyperparathyroidism","volume":"35","author":"Valdimarsson","year":"2000","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.jpeds.2008.03.003","article-title":"Bone metabolism in celiac disease","volume":"153","author":"Zanchi","year":"2008","journal-title":"J. Pediatr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1002\/jpn3.12126","article-title":"Status of vitamins and minerals in children with screening-identified celiac disease: A case-control study","volume":"78","author":"Troncone","year":"2024","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Russell, L.A., Alliston, P., Armstrong, D., Verdu, E.F., Moayyedi, P., and Pinto-Sanchez, M.I. (2025). Micronutrient Deficiencies Associated with a Gluten-Free Diet in Patients with Celiac Disease and Non-Celiac Gluten or Wheat Sensitivity: A Systematic Review and Meta-Analysis. J. Clin. Med., 14.","DOI":"10.3390\/jcm14144848"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.5152\/tjg.2022.21815","article-title":"The Investigation of Nutritional Status, Intestinal Permeability, and Quality of Life in People with Celiac Disease","volume":"33","year":"2022","journal-title":"Turk. J. Gastroenterol."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/6\/730\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T04:17:55Z","timestamp":1779769075000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/13\/6\/730"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,24]]},"references-count":52,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["children13060730"],"URL":"https:\/\/doi.org\/10.3390\/children13060730","relation":{},"ISSN":["2227-9067"],"issn-type":[{"value":"2227-9067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,24]]}}}