{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:57:08Z","timestamp":1793314628958,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,1,10]],"date-time":"2019-01-10T00:00:00Z","timestamp":1547078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health and Lumbardy\u2019s Regional Government Authority (Ministero della Salute and Regione Lombardia)","award":["2011-02348234"],"award-info":[{"award-number":["2011-02348234"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>It is unclear whether patients with non-celiac gluten sensitivity (NCGS) can tolerate gluten. We have evaluated the changes of both gastrointestinal symptoms and quality of life for NCGS patients after the re-introduction of dietary gluten. Twenty-two NCGS patients reporting functional gastroenterological symptoms and on gluten-free diet (GFD) for the previous three weeks were exposed to incremental gluten-containing diets. Three groups were compared at baseline (immediately after 3-weeks on GFD) and immediately after the return of symptomatology: (i) a group tolerating a low-gluten diet (3.5 g gluten\/day, week 1, n = 8), (ii) a group tolerating a mid-gluten diet (8 g gluten\/day, week 2, n = 6), and (iii) a group tolerating a high-gluten diet (13 g gluten\/day, week 3, n = 8). Their gastrointestinal symptoms and quality of life were assessed at baseline and post-intervention. The most common symptoms were: constipation (46%), abdominal pain (50%) and dyspepsia (38%). A decrease in several short form health survey (SF-36) sub-scores (all p &lt; 0.03) after gluten re-introduction was only observed in the group tolerating the low-gluten diet; the same group showed a lower post-intervention role-emotional SF-36 score (p = 0.01). Most gastrointestinal symptoms remained similar after gluten re-introduction. However, a decrease in the general perception of well-being was only found after gluten re-introduction in the group tolerating a low-gluten diet (p = 0.01); the same was true when comparing the post-intervention general well-being perception among the three groups (p = 0.050). In conclusion, dissimilar responses from patients with NCGS were observed after the re-introduction of gluten, with gluten at a low dosage affecting the quality of life and general well-being of a group of patients, whereas others tolerate even higher doses of dietary gluten.<\/jats:p>","DOI":"10.3390\/nu11010136","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T04:10:16Z","timestamp":1547179816000},"page":"136","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Exposure to Different Amounts of Dietary Gluten in Patients with Non-Celiac Gluten Sensitivity (NCGS): An Exploratory Study"],"prefix":"10.3390","volume":"11","author":[{"given":"Leda","family":"Roncoroni","sequence":"first","affiliation":[{"name":"Center for Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20135 Milan, Italy"},{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3759-2121","authenticated-orcid":false,"given":"Karla A.","family":"Bascu\u00f1\u00e1n","sequence":"additional","affiliation":[{"name":"Center for Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20135 Milan, Italy"},{"name":"Department of Nutrition, School of Medicine, University of Chile, 8380453 Santiago, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Vecchi","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy"},{"name":"Gastroenterology and Endoscopic Unit, Fondazione IRCCS Ca\u2019 Granda, Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Doneda","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria T.","family":"Bardella","sequence":"additional","affiliation":[{"name":"Center for Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20135 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenza","family":"Lombardo","sequence":"additional","affiliation":[{"name":"Center for Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20135 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Scricciolo","sequence":"additional","affiliation":[{"name":"Center for Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20135 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9217-8241","authenticated-orcid":false,"given":"Federica","family":"Branchi","sequence":"additional","affiliation":[{"name":"Center for Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20135 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Elli","sequence":"additional","affiliation":[{"name":"Center for Prevention and Diagnosis of Celiac Disease, Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20135 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,1,10]]},"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. (2012). Spectrum of gluten-related disorders: Consensus on new nomenclature and classification. BMC Med., 10.","DOI":"10.1186\/1741-7015-10-13"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1093\/nutrit\/nux068","article-title":"The 5 Ws of a gluten challenge for gluten-related disorders","volume":"76","author":"Roncoroni","year":"2018","journal-title":"Nutr. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3839","DOI":"10.3390\/nu5103839","article-title":"Non-celiac gluten sensitivity: The new frontier of gluten related disorders","volume":"5","author":"Catassi","year":"2013","journal-title":"Nutrients"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4966","DOI":"10.3390\/nu7064966","article-title":"Diagnosis of non-celiac gluten sensitivity (NCGS): The salerno experts\u2019 criteria","volume":"7","author":"Catassi","year":"2015","journal-title":"Nutrients"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/ajg.2010.487","article-title":"Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease: A Double-Blind Randomized Placebo-Controlled Trial","volume":"106","author":"Biesiekierski","year":"2011","journal-title":"Am. J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Volta, U., Bardella, M.T., Calabr\u00f2, A., Troncone, R., Corazza, G.R., Bagnato, C., Belcari, C., Bellantoni, A., Caio, G., and Calella, F. (2014). An Italian prospective multicenter survey on patients suspected of having non-celiac gluten sensitivity. BMC Med., 12.","DOI":"10.1186\/1741-7015-12-85"},{"key":"ref_7","first-page":"40","article-title":"Non-Celiac Gluten Sensitivity; Where are we now in 2015?","volume":"142","author":"Parrish","year":"2015","journal-title":"Pract. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1053\/j.gastro.2014.12.049","article-title":"Nonceliac gluten sensitivity","volume":"148","author":"Fasano","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"621","DOI":"10.3389\/fphys.2017.00621","article-title":"Re-challenge Studies in Non-celiac Gluten Sensitivity: A Systematic Review and Meta-Analysis","volume":"8","author":"Lionetti","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.cgh.2016.08.007","article-title":"Suspected Nonceliac Gluten Sensitivity Confirmed in Few Patients After Gluten Challenge in Double-Blind, Placebo-Controlled Trials","volume":"15","author":"Carroccio","year":"2017","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/ajg.2013.79","article-title":"ACG clinical guidelines: Diagnosis and management of celiac disease","volume":"108","author":"Hill","year":"2013","journal-title":"Am. J. Gastroenterol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1111\/j.1365-277X.2005.00591.x","article-title":"\u201cControlled by food\u201d\u2014Lived experiences of coeliac disease","volume":"18","author":"Sverker","year":"2005","journal-title":"J. Hum. Nutr. Diet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s00394-016-1238-5","article-title":"Celiac disease: Understanding the gluten-free diet","volume":"56","author":"Vespa","year":"2017","journal-title":"Eur. J. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1097\/MPG.0000000000001216","article-title":"NASPGHAN clinical report on the diagnosis and treatment of gluten-related disorders","volume":"63","author":"Hill","year":"2016","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Catassi, C., Alaedini, A., Bojarski, C., Bonaz, B., Bouma, G., Carroccio, A., Castillejo, G., De Magistris, L., Dieterich, W., and Di Liberto, D. (2017). The overlapping area of non-celiac gluten sensitivity (NCGS) and wheat-sensitive irritable bowel syndrome (IBS): An update. Nutrients, 9.","DOI":"10.3390\/nu9111268"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1136\/gutjnl-2016-311964","article-title":"Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease","volume":"65","author":"Uhde","year":"2016","journal-title":"Gut"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Pinto-S\u00e1nchez, M.I., and Verd\u00fa, E.F. (2016). Non-coeliac gluten sensitivity: Are we closer to separating the wheat from the chaff?. Gut.","DOI":"10.1136\/gutjnl-2016-312471"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1084\/jem.20102660","article-title":"Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4","volume":"209","author":"Junker","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"771","DOI":"10.3390\/nu5030771","article-title":"The dietary intake of wheat and other cereal grains and their role in inflammation","volume":"5","author":"Pruimboom","year":"2013","journal-title":"Nutrients"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.1111\/j.1365-2222.2008.03101.x","article-title":"Allergens to wheat and related cereals","volume":"38","author":"Tatham","year":"2008","journal-title":"Clin. Exp. Allergy"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.taap.2009.03.012","article-title":"Effects of wheat germ agglutinin on human gastrointestinal epithelium: Insights from an experimental model of immune\/epithelial cell interaction","volume":"237","author":"Pellegrina","year":"2009","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.coph.2018.09.003","article-title":"Use of dietary interventions for functional gastrointestinal disorders","volume":"43","author":"Manning","year":"2018","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Roncoroni, L., Bascu\u00f1\u00e1n, K.A., Doneda, L., Scricciolo, A., Lombardo, V., Branchi, F., Ferretti, F., Dell\u2019osso, B., Montanari, V., and Bardella, M.T. (2018). A low FODMAP gluten-free diet improves functional gastrointestinal disorders and overall mental health of celiac disease patients: A randomized controlled trial. Nutrients, 10.","DOI":"10.3390\/nu10081023"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1038\/ajg.2012.236","article-title":"Non-celiac wheat sensitivity diagnosed by double-blind placebo-controlled challenge: Exploring a new clinical entity","volume":"107","author":"Carroccio","year":"2012","journal-title":"Am. J. Gastroenterol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1111\/apt.12730","article-title":"Randomised clinical trial: Gluten may cause depression in subjects with non-coeliac gluten sensitivity\u2014An exploratory clinical study","volume":"39","author":"Peters","year":"2014","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1111\/apt.13372","article-title":"Randomised clinical study: Gluten challenge induces symptom recurrence in only a minority of patients who meet clinical criteria for non-coeliac gluten sensitivity","volume":"42","author":"Zanini","year":"2015","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000430090","article-title":"Non-Celiac Gluten Sensitivity among Patients Perceiving Gluten-Related Symptoms","volume":"92","author":"Capannolo","year":"2015","journal-title":"Digestion"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Rosinach, M., Fern\u00e1ndez-Ba\u00f1ares, F., Carrasco, A., Ibarra, M., Temi\u00f1o, R., Salas, A., and Esteve, M. (2016). Double-Blind Randomized Clinical Trial: Gluten versus Placebo Rechallenge in Patients with Lymphocytic Enteritis and Suspected Celiac Disease. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0157879"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1097\/MCG.0000000000000515","article-title":"Intestinal, systemic, and oral gluten-related alterations in patients with nonceliac gluten sensitivity","volume":"50","author":"Picarelli","year":"2016","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Elli, L., Tomba, C., Branchi, F., Roncoroni, L., Lombardo, V., Bardella, M.T., Ferretti, F., Conte, D., Valiante, F., and Fini, L. (2016). Evidence for the presence of non-celiac gluten sensitivity in patients with functional gastrointestinal symptoms: Results from a multicenter randomized double-blind placebo-controlled gluten challenge. Nutrients, 8.","DOI":"10.3390\/nu8020084"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1053\/j.gastro.2017.10.040","article-title":"Fructan, Rather Than Gluten, Induces Symptoms in Patients With Self-Reported Non-Celiac Gluten Sensitivity","volume":"154","author":"Skodje","year":"2018","journal-title":"Gastroenterology"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Dale, H.F., Hatlebakk, J.G., Hovdenak, N., Ystad, S.O., and Lied, G.A. (2018). The effect of a controlled gluten challenge in a group of patients with suspected non-coeliac gluten sensitivity: A randomized, double-blind placebo-controlled challenge. Neurogastroenterol. Motil., e13332.","DOI":"10.26226\/morressier.59a6b349d462b80290b553ae"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/cmi.2013.28","article-title":"Non-celiac gluten sensitivity: Questions still to be answered despite increasing awareness","volume":"10","author":"Volta","year":"2013","journal-title":"Cell. Mol. Immunol."},{"key":"ref_34","first-page":"237","article-title":"Rome III: New standard for functional gastrointestinal disorders","volume":"15","author":"Drossman","year":"2006","journal-title":"J. Gastrointest. Liver Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.cgh.2008.12.032","article-title":"A Simple Validated Gluten-Free Diet Adherence Survey for Adults With Celiac Disease","volume":"7","author":"Leffler","year":"2009","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Schalk, K., Lexhaller, B., Koehler, P., and Scherf, K.A. (2017). Isolation and characterization of gluten protein types from wheat, rye, barley and oats for use as reference materials. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0172819"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Ware, J.E., and Sherbourne, C.D. (1992). The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med. Care, 473\u2013483.","DOI":"10.1097\/00005650-199206000-00002"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1016\/j.cgh.2015.01.029","article-title":"Small Amounts of Gluten in Subjects With Suspected Nonceliac Gluten Sensitivity: A Randomized, Double-Blind, Placebo-Controlled, Cross-Over Trial","volume":"13","author":"Volta","year":"2015","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4542","DOI":"10.3390\/nu7064542","article-title":"Non-Celiac Gluten Sensitivity Has Narrowed the Spectrum of Irritable Bowel Syndrome: A Double-Blind Randomized Placebo-Controlled Trial","volume":"7","author":"Shahbazkhani","year":"2015","journal-title":"Nutrients"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1038\/ajg.2012.344","article-title":"Editorial: Non-celiac wheat sensitivity: Separating the wheat from the chat!","volume":"107","author":"Sanders","year":"2012","journal-title":"Am. J. Gastroenterol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1053\/j.gastro.2013.08.061","article-title":"Non-celiac wheat sensitivity is a more appropriate label than non-celiac gluten sensitivity","volume":"146","author":"Carroccio","year":"2014","journal-title":"Gastroenterology"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/1\/136\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:25:00Z","timestamp":1760185500000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/1\/136"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1,10]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,1]]}},"alternative-id":["nu11010136"],"URL":"https:\/\/doi.org\/10.3390\/nu11010136","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1,10]]}}}