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

Abstract

PurposeIrritable 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).MethodsThe 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.ResultsThirty-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.ConclusionUsing 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00384-016-2663-x) contains supplementary material, which is available to authorized users.

Dietary therapies for functional bowel symptoms: Recent advances, challenges, and future directions

“…Non‐randomized clinical trials: Two studies have shown improved symptoms following 4‐6 month use of the gluten‐free diet in IBS …”

“…Trials assessing effect by genotype: One RCT showed greatest effect in HLA‐DQ2/8‐positive patients; another showed improvement in 60% of HLA‐DQ2‐positive patients and only 12% who were HLA‐DQ2‐negative . While another study showed no association between genotyping and response …”

“…Non-randomized clinical trials: Two studies have shown improved symptoms following 4-6 month use of the gluten-free diet in IBS. 141,142 Trials assessing effect by genotype: One RCT showed greatest effect in HLA-DQ2/8-positive patients 137 ; another showed improvement in 60% of HLA-DQ2-positive patients and only 12% who were HLA-DQ2-negative. 141 While another study showed no association between genotyping and response.…”

“…141 While another study showed no association between genotyping and response. 142 Animal models: Alterations in gut function have been observed in mice in response to gluten challenge, including muscle hyper contractility in HLA-DQ8 transgenic mice, 143 and increased transcellular macromolecular transport in HLA-DQ8/HCD4 mice. 144 How this translates in patients with IBS requires elucidation.…”

Modulation of the gut microbiota: a focus on treatments for irritable bowel syndrome

“…Because studies have shown that a gluten-free diet can improve IBS symptoms, at least in some patients, nonceliac wheat sensitivity may comprise a subset of patients with IBS [40,42]. A gluten-free diet was also shown to improve IBS-related QOL from baseline in some patients with IBS [43]. This may partly be related to GI mucosal changes observed in patients with IBS with a suspected food intolerance; these changes include epithelial barrier disruptions, fluid secretion into the GI lumen, and an influx of intraepithelial lymphocytes [44].…”