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Int J Colorectal Dis. 2017 Jan;32(1):29-39. doi: 10.1007/s00384-016-2663-x. Epub 2016 Sep 30.

Long-term response to gluten-free diet as evidence for non-celiac wheat sensitivity in one third of patients with diarrhea-dominant and mixed-type irritable bowel syndrome.

Author information

Medical Department, Division of Gastroenterology, Infectiology, and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany.
Institute of Clinical Physiology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Department of Dermatology and Allergy, Allergy-Centre-Charité, Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Department of Medical Microbiology, Immunology, and Hygiene, Technische Universität, Munich, Germany.
Medical Department, Division of Gastroenterology, Infectiology, and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany.



Irritable bowel syndrome (IBS) is common but therapies are unsatisfactory. Food is often suspected as cause by patients, but diagnostic procedures, apart from allergy testing, are limited. Based on the hypothesis of non-celiac wheat sensitivity (WS) in a subgroup of IBS patients, we tested the long-term response to a gluten-free diet (GFD) and investigated HLA-DQ2 or -DQ8 expression as a diagnostic marker for WS in diarrhea-dominant (IBS-D) and mixed-type IBS (IBS-M).


The response to a GFD served as reference test for WS and HLA-DQ2/8 expression was determined as index test. Patients were classified as responders if they reported complete or considerable relief of IBS symptoms on at least 75 % of weeks over a 4-month period of gluten-free diet. Established questionnaires (IBS-Quality of Life (IBS-QoL), IBS Symptom Severity Scale (IBS-SSS), European Quality of Life-5 Dimensions (EQ-5D)) were used for secondary outcome measures.


Thirty-five patients finished the study. Of these, 12 (34 %) were responders and classified as having WS (95 % CI 21-51 %). HLA-DQ2/8 expression had a specificity of 52 % (95 % CI 33-71 %) and sensitivity of 25 % (95 % CI 8-54 %) for WS. Responders showed improvement in quality of life and symptom scores. At 1-year follow-up, all responders and 55 % of non-responders were still on GFD and reported symptom relief.


Using strict criteria as recommended for IBS studies, about one third of patients with IBS-D or IBS-M are wheat sensitive, with a similar proportion in both IBS types. Expression of HLA-DQ2/8 is not useful as diagnostic marker for WS. Long-term adherence to a GFD is high and can sustain symptomatic improvement.


Gluten-free diet; HLA-DQ2; HLA-DQ8; Irritable bowel syndrome; Wheat-sensitivity

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Conflict of interest statement

Compliance with ethical standards The study was approved by the local ethics committee of the Charité—Universitätsmedizin Berlin under the number EA4/044/11. Written informed consent was obtained from all study participants. Funding The study was initiated by the investigators and supported by a grant from Dr. Schär AG. Conflict of interest Reiner Ullrich and Michael Schumann received research grants from Dr. Schär AG. Britta Siegmund received a research grant from Hospira and served as consultant for Janssen, MSD, Abbvie, Takeda, Hospira and received lecture fees from Abbvie, Falk, Ferring, MSD, Merck, Takeda; all money went to the institution. Torsten Zuberbier served as a consultant for ALK, Almirall, Abbvie, Astellas, Bayer Health Care, Bencard, Berlin Chemie, FAES, HAL, Henkel, Kryolan, Leti, Meda, Menarini, Merck, MSD, Novartis, Pharmasquire, Quintiles, Serono, Stallergenes, Takeda, Teva, and UCB. Christian Barmeyer, Tim Meyer, Christina Zielinski, Jörg-Dieter Schulzke, and Severin Daum declare that they have no conflict of interest. Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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