No effects of gluten in patients with self-reported non-celiac gluten sensitivity after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates.

BACKGROUND & AIMS Patients with non-celiac gluten sensitivity (NCGS) do not have celiac disease but their symptoms improve when they are placed on gluten-free diets. We investigated the specific effects of gluten after dietary reduction of fermentable, poorly absorbed, short-chain carbohydrates (fermentable, oligo-, di-, monosaccharides, and polyols [FODMAPs]) in subjects believed to have NCGS. METHODS We performed a double-blind cross-over trial of 37 subjects (aged 24-61 y, 6 men) with NCGS and irritable bowel syndrome (based on Rome III criteria), but not celiac disease. Participants were randomly assigned to groups given a 2-week diet of reduced FODMAPs, and were then placed on high-gluten (16 g gluten/d), low-gluten (2 g gluten/d and 14 g whey protein/d), or control (16 g whey protein/d) diets for 1 week, followed by a washout period of at least 2 weeks. We assessed serum and fecal markers of intestinal inflammation/injury and immune activation, and indices of fatigue. Twenty-two participants then crossed over to groups given gluten (16 g/d), whey (16 g/d), or control (no additional protein) diets for 3 days. Symptoms were evaluated by visual analogue scales. RESULTS In all participants, gastrointestinal symptoms consistently and significantly improved during reduced FODMAP intake, but significantly worsened to a similar degree when their diets included gluten or whey protein. Gluten-specific effects were observed in only 8% of participants. There were no diet-specific changes in any biomarker. During the 3-day rechallenge, participants' symptoms increased by similar levels among groups. Gluten-specific gastrointestinal effects were not reproduced. An order effect was observed. CONCLUSIONS In a placebo-controlled, cross-over rechallenge study, we found no evidence of specific or dose-dependent effects of gluten in patients with NCGS placed diets low in FODMAPs.

[1]  B. Powell,et al.  Rapid disruption of intestinal barrier function by gliadin involves altered expression of apical junctional proteins , 2005, FEBS letters.

[2]  Jean-Michel Antoine,et al.  Guidelines for the design, conduct and reporting of human intervention studies to evaluate the health benefits of foods , 2011, British Journal of Nutrition.

[3]  G. Corazza,et al.  A gluten-free diet score to evaluate dietary compliance in patients with coeliac disease. , 2009, The British journal of nutrition.

[4]  Jane G Muir,et al.  Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease: A Double-Blind Randomized Placebo-Controlled Trial , 2011, The American Journal of Gastroenterology.

[5]  T. Kaptchuk.  The double-blind, randomized, placebo-controlled trial: gold standard or golden calf? , 2001, Journal of clinical epidemiology.

[6]  Peter HR Green,et al.  Spectrum of gluten-related disorders: consensus on new nomenclature and classification , 2012, BMC Medicine.

[7]  B. Walker,et al.  Rural Industries Research and Development Corporation , 2011 .

[8]  P. Gibson,et al.  Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo-controlled evidence. , 2008, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[9]  J. Fisk,et al.  Construction and validation of a fatigue impact scale for daily administration (D-FIS) , 2002, Quality of Life Research.

[10]  D. Jewell,et al.  T cells in peripheral blood after gluten challenge in coeliac disease , 2005, Gut.

[11]  M. Soresi,et al.  Non-Celiac Wheat Sensitivity Diagnosed by Double-Blind Placebo-Controlled Challenge: Exploring a New Clinical Entity , 2012, The American Journal of Gastroenterology.

[12]  Stewart G Trost,et al.  Conducting accelerometer-based activity assessments in field-based research. , 2005, Medicine and science in sports and exercise.

[13]  W. Chey,et al.  The prevalence of celiac disease among patients with nonconstipated irritable bowel syndrome is similar to controls. , 2011, Gastroenterology.

[14]  K. Klein.  Controlled treatment trials in the irritable bowel syndrome: a critique. , 1988, Gastroenterology.

[15]  J. Schulzke,et al.  Celiac disease-like abnormalities in a subgroup of patients with irritable bowel syndrome. , 2001, Gastroenterology.

[16]  R. Ford.  The gluten syndrome: a neurological disease. , 2009, Medical hypotheses.

[17]  P. Gibson,et al.  Measurement of short-chain carbohydrates in common Australian vegetables and fruits by high-performance liquid chromatography (HPLC). , 2009, Journal of agricultural and food chemistry.

[18]  F. Tovoli,et al.  Serological Tests in Gluten Sensitivity (Nonceliac Gluten Intolerance) , 2012, Journal of clinical gastroenterology.

[19]  D. Sanders,et al.  The Oslo definitions for coeliac disease and related terms , 2012, Gut.

[20]  T. Libermann,et al.  Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4 , 2012, The Journal of experimental medicine.

[21]  M. Zeitz,et al.  Predictors of clinical response to gluten-free diet in patients diagnosed with diarrhea-predominant irritable bowel syndrome. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[22]  G. Anastasi,et al.  Scanning Electron Microscopy of Histological Relapse after Gluten‐Challenge in Coeliac Disease , 1989, Acta paediatrica Scandinavica.

[23]  P. Gibson,et al.  Fructan and free fructose content of common Australian vegetables and fruit. , 2007, Journal of agricultural and food chemistry.

[24]  Peter R. Gibson,et al.  Proton Pump Inhibitor Therapy Use Does Not Predispose to Small Intestinal Bacterial Overgrowth , 2011, The American Journal of Gastroenterology.

[25]  Valeria Panebianco,et al.  Supplementary Figure 2 , 2012 .

[26]  B. Popkin,et al.  Determinants of adolescent physical activity and inactivity patterns. , 2000, Pediatrics.

[27]  P. Gibson,et al.  Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome , 2010, Journal of gastroenterology and hepatology.

[28]  B. Beaufrère,et al.  Slow and fast dietary proteins differently modulate postprandial protein accretion. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[29]  E. Straface,et al.  Induction of apoptosis in caco-2 cells by wheat gliadin peptides. , 2000, Toxicology.