{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T22:34:36Z","timestamp":1779143676290,"version":"3.51.4"},"reference-count":37,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,15]],"date-time":"2022-06-15T00:00:00Z","timestamp":1655251200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined. Villus height (VH, in \u03bcm), crypt depth (CrD, in \u03bcm), villus-to-crypt ratios (VCR), IELs (intraepithelial lymphocytes\/100 enterocytes), and other relevant histological, serologic, and demographic parameters were quantified. Results: The median VH in NCGS was significantly shorter (600, IQR: 400\u2013705) than controls (900, IQR: 667\u20131112) (p &lt; 0.001). NCGS patients with Marsh I-II had similar VH and VCR to CeD [465 \u00b5m (IQR: 390\u2013620) vs. 427 \u00b5m (IQR: 348\u2013569, p = 0\u00b7176)]. The VCR in NCGS with Marsh 0 was lower than controls (p &lt; 0.001). The median IEL in NCGS with Marsh 0 was higher than controls (23.0 vs. 13.7, p &lt; 0.001). To distinguish Marsh 0 NCGS from controls, an IEL cut-off of 14 showed 79% sensitivity and 55% specificity. IEL densities in Marsh I-II NCGS and CeD groups were similar. Conclusion: NCGS duodenal mucosa exhibits distinctive changes consistent with an intestinal response to luminal antigens, even at the Marsh 0 stage of villus architecture.<\/jats:p>","DOI":"10.3390\/nu14122487","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T03:01:22Z","timestamp":1655348482000},"page":"2487","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2114-2353","authenticated-orcid":false,"given":"Kamran","family":"Rostami","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Palmerston North District Health Board (DHB), Palmerston North 4442, New Zealand"},{"name":"Gastroenterology Unit, Milton Keynes University Hospital, Milton Keynes MK6 5LD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arzu","family":"Ensari","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ankara University Medical School, Ankara 06620, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6269-6793","authenticated-orcid":false,"given":"Michael N.","family":"Marsh","sequence":"additional","affiliation":[{"name":"Oxford & Department of Gastroenterology, Wolfson College, University of Oxford, Luton & Dunstable University Hospital Trust, Bedfordshire LU4 0DZ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amitabh","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincenzo","family":"Villanacci","sequence":"additional","affiliation":[{"name":"Spedali Civili, Institute of Pathology, 25100 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8913-7916","authenticated-orcid":false,"given":"Antonio","family":"Carroccio","sequence":"additional","affiliation":[{"name":"Palermo, Internal Medicine Unit, Department \u2018PROMISE\u2019, University of Palermo, \u201cV. Cervello Hospital\u201d, 90100 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5589-8856","authenticated-orcid":false,"given":"Hamid","family":"Asadzadeh Aghdaei","sequence":"additional","affiliation":[{"name":"Gastroenterology and Liver Diseases Reseach Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julio C.","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Medicine, Dr. C. Bonorino Udaondo Gastroenterology Hospital, Buenos Aires 1264, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0237-1812","authenticated-orcid":false,"given":"Gabrio","family":"Bassotti","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Perugia School of Medicine, 06129 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Becheanu","sequence":"additional","affiliation":[{"name":"Department of Pathology, Carol Davila University of Medicine & Pharmacy, 050474 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3040-1548","authenticated-orcid":false,"given":"Phoenix","family":"Bell","sequence":"additional","affiliation":[{"name":"Gastrointestinal Pathology Center of Excellence University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camillo","family":"Di Bella","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Milan-Bicocca, 20900 Monza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maria","family":"Bozzola","sequence":"additional","affiliation":[{"name":"Spedali Civili, Institute of Pathology, 25100 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moris","family":"Cadei","sequence":"additional","affiliation":[{"name":"Spedali Civili, Institute of Pathology, 25100 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0710-4182","authenticated-orcid":false,"given":"Giovanni","family":"Casella","sequence":"additional","affiliation":[{"name":"Medical Deptartment, Desio Hospital, 20832 Desio, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Catassi","sequence":"additional","affiliation":[{"name":"Deptartment of Pediatrics, Universita Politecnica delle Marche, 60123 Ancona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7426-1145","authenticated-orcid":false,"given":"Carolina","family":"Ciacci","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina, Chirurgia e Odontoiatria, Scuola Medica Salernitana, Universit\u00e0 di Salerno Gastroenterologia, 84084 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4761-4133","authenticated-orcid":false,"given":"Delia Gabriela","family":"Apostol Ciobanu","sequence":"additional","affiliation":[{"name":"Pathology Department, Grigore T. Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon S.","family":"Cross","sequence":"additional","affiliation":[{"name":"Gastroenterology and Pathology, Sheffield Teaching Hospitals, Sheffield S10 2JF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0194-7832","authenticated-orcid":false,"given":"Mihai","family":"Danciu","sequence":"additional","affiliation":[{"name":"Pathology Department, Grigore T. 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Giaccone\u201d, 17491 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9101-9131","authenticated-orcid":false,"given":"Nicola","family":"Fusco","sequence":"additional","affiliation":[{"name":"Division of Pathology, Fondazione IRCSS Ca\u2019 Granda-Ospedale Maggiore Policlinico, University of Milan, 20832 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James J.","family":"Going","sequence":"additional","affiliation":[{"name":"Department of Pathology, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7316-7384","authenticated-orcid":false,"given":"Stefano","family":"Guandalini","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Chicago Medicine, Chicago, IL 60637, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine E.","family":"Hagen","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN 55907, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0087-3015","authenticated-orcid":false,"given":"David T. 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Popa University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khun","family":"La Win Myint","sequence":"additional","affiliation":[{"name":"Department of Pathology, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6343-2236","authenticated-orcid":false,"given":"Hamid","family":"Mohaghegh-Shalmani","sequence":"additional","affiliation":[{"name":"Gastroenterology and Liver Diseases Reseach Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Afshin","family":"Moradi","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris J. J.","family":"Mulder","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, 1081 HV Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronnie","family":"Ray","sequence":"additional","affiliation":[{"name":"Luton Dunstable University Hospital, Gastroenterology, Luton LU4 0DZ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0748-6600","authenticated-orcid":false,"given":"Chiara","family":"Ricci","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Sciences, University of Brescia, 25100 Brescia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2495-1831","authenticated-orcid":false,"given":"Mohammad","family":"Rostami-Nejad","sequence":"additional","affiliation":[{"name":"Gastroenterology and Liver Diseases Reseach Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran 1985717411, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Sapone","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Center for Celiac Research & Treatment, Boston, MA 02114, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Sanders","sequence":"additional","affiliation":[{"name":"Gastroenterology and Pathology, Sheffield Teaching Hospitals, Sheffield S10 2JF, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3948-9555","authenticated-orcid":false,"given":"Juha","family":"Taavela","sequence":"additional","affiliation":[{"name":"Central Finland Central Hospital, 33520 Jyv\u00e4skyl\u00e4, Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0872-3089","authenticated-orcid":false,"given":"Umberto","family":"Volta","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, University of Bologna, 40126 Bologna, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7788-0056","authenticated-orcid":false,"given":"Marjorie","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, College of Health, Medicine and Wellbeing, University of Newcastle, Callaghan, NSW 2308, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Derakhshan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Queen Elizabeth University Hospital, Glasgow G51 4TF, UK"},{"name":"College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sapone, A., Bai, J.C., Ciacci, C., Dolinsek, J., Green, P.H.R., Hadjivassiliou, M., Kaukinen, K., Rostami, K., Sanders, D.S., and Schumann, M. 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