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.
OBJECTIVE
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
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.
Christian
C
Barmeyer
Medical Department, Division of Gastroenterology, Infectiology, and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany.
Michael
M
Schumann
Medical Department, Division of Gastroenterology, Infectiology, and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany.
Tim
T
Meyer
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.
Christina
C
Zielinski
Department of Dermatology and Allergy, Allergy-Centre-Charité, Campus Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Torsten
T
Zuberbier
Medical Department, Division of Gastroenterology, Infectiology, and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany.
Britta
B
Siegmund
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.
Jörg-Dieter
JD
Schulzke
Medical Department, Division of Gastroenterology, Infectiology, and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany.
Severin
S
Daum
Medical Department, Division of Gastroenterology, Infectiology, and Rheumatology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Hindenburgdamm 30, 12200, Berlin, Germany. reiner.ullrich@charite.de.
Reiner
R
Ullrich
D000328:Adult; D000368:Aged; D002446:Celiac Disease / Q000150:complications*; D003967:Diarrhea / Q000150:complications* / Q000178:diet therapy*; D055050:Diet, Gluten-Free; D005247:Feeding Behavior; D005260:Female; D005500:Follow-Up Studies; D006683:HLA-DQ Antigens / Q000276:immunology; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000150:complications* / Q000178:diet therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014908:Triticum / Q000009:adverse effects*
D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen
Gluten-free diet; HLA-DQ2; HLA-DQ8; Irritable bowel syndrome; Wheat-sensitivity
Gastroenterology. 2013 May;144(5):903-911.e3
23357715
Am J Gastroenterol. 2007 Jul;102(7):1454-60
17355413
Am J Gastroenterol. 2012 Dec;107(12):1898-906; quiz 1907
22825366
Dig Dis Sci. 1998 Feb;43(2):400-11
9512138
Gastroenterology. 2014 Nov;147(5):1012-20.e4
25083606
J Clin Epidemiol. 2003 Apr;56(4):310-6
12767407
Gastroenterology. 2005 Apr;128(4 Suppl 1):S74-8
15825130
Digestion. 2015;92(1):22-31
26044145
Gastroenterology. 2001 Dec;121(6):1329-38
11729112
Aliment Pharmacol Ther. 2001 Oct;15(10):1655-66
11564007
Lancet. 2001 Nov 3;358(9292):1504-8
11705563
Aliment Pharmacol Ther. 1997 Apr;11(2):395-402
9146781
Eur J Gastroenterol Hepatol. 2003 Apr;15(4):407-13
12655262
Clin Gastroenterol Hepatol. 2007 Jul;5(7):844-50; quiz 769
17553753
Gastroenterology. 1991 Oct;101(4):927-34
1889716
Eur J Gastroenterol Hepatol. 2007 Feb;19 Suppl 1:S11-37
17325546
Dig Dis Sci. 1995 Dec;40(12):2647-55
8536526
Nutrients. 2013 Sep 26;5(10):3839-53
24077239
Aliment Pharmacol Ther. 2003 Oct 1;18(7):671-82
14510740
Gastroenterology. 2015 Sep;149(3):596-603.e1
26026392
J Exp Med. 1989 Jan 1;169(1):345-50
2909659
J Exp Med. 2012 Dec 17;209(13):2395-408
23209313
Arch Intern Med. 2003 Apr 28;163(8):929-35
12719202
Gut. 2013 Jan;62(1):43-52
22345659
Clin Gastroenterol Hepatol. 2016 May;14 (5):696-703.e1
26748221
Am J Gastroenterol. 2011 Mar;106(3):508-14; quiz 515
21224837
Gastroenterology. 1991 Apr;100(4):998-1005
2001837
BMC Med. 2012 Feb 07;10:13
22313950
Z Gastroenterol. 2013 Oct;51(10):1171-6
24122378
Aliment Pharmacol Ther. 2014 May;39(10):1104-12
24689456
Gastroenterology. 2015 May;148(6):1195-204
25583468
Rofo. 2002 Nov;174(11):1438-44
12424672
BMJ. 2012 Sep 04;345:e5836
22951548
Pharmacoeconomics. 1992 May;1(5):312-24
10146996
Lancet. 2003 Aug 2;362(9381):383-91
12907013
Gastroenterology. 2013 Aug;145(2):320-8.e1-3
23648697
Am J Gastroenterol. 2000 Apr;95(4):999-1007
10763950
BMC Med. 2014 May 23;12:85
24885375
Allergy. 2004 Mar;59(3):338-45
14982518
Am J Gastroenterol. 2014 Aug;109 Suppl 1:S2-26; quiz S27
25091148
Aliment Pharmacol Ther. 2003 Jul 15;18(2):231-5
12869084