Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease: A Double-Blind Randomized Placebo-Controlled Trial

• Published in: The American journal of gastroenterology Vol. 106; no. 3; pp. 508 - 514
• Main Authors: Biesiekierski, Jessica R, Newnham, Evan D, Irving, Peter M, Barrett, Jacqueline S, Haines, Melissa, Doecke, James D, Shepherd, Susan J, Muir, Jane G, Gibson, Peter R
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.03.2011; Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Biological and medical sciences; Biomarkers - blood; Celiac disease; Celiac Disease - diagnosis; Colitis - chemically induced; Diet, Gluten-Free; Double-Blind Method; Enteritis - chemically induced; Female; Gastroenterology; Gastroenterology. Liver. Pancreas. Abdomen; Gastrointestinal Tract - drug effects; Gastrointestinal Tract - immunology; Gastrointestinal Tract - physiopathology; Glutens - adverse effects; Glutens - immunology; Humans; Irritable Bowel Syndrome - immunology; Irritable Bowel Syndrome - physiopathology; Male; Medical sciences; Middle Aged; Other diseases. Semiology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Treatment Outcome; Human; Immunopathology; Symptomatology; Intestinal malabsorption; Gastroenterology; Digestive diseases; Intestinal disease; Gastrointestinal; Coeliac disease; Gluten
• ISSN: 0002-9270; 1572-0241; 1572-0241
• DOI: 10.1038/ajg.2010.487

Despite increased prescription of a gluten-free diet for gastrointestinal symptoms in individuals who do not have celiac disease, there is minimal evidence that suggests that gluten is a trigger. The aims of this study were to determine whether gluten ingestion can induce symptoms in non-celiac individuals and to examine the mechanism. A double-blind, randomized, placebo-controlled rechallenge trial was undertaken in patients with irritable bowel syndrome in whom celiac disease was excluded and who were symptomatically controlled on a gluten-free diet. Participants received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. Symptoms were evaluated using a visual analog scale and markers of intestinal inflammation, injury, and immune activation were monitored. A total of 34 patients (aged 29-59 years, 4 men) completed the study as per protocol. Overall, 56% had human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8. Adherence to diet and supplements was very high. Of 19 patients (68%) in the gluten group, 13 reported that symptoms were not adequately controlled compared with 6 of 15 (40%) on placebo (P=0.0001; generalized estimating equation). On a visual analog scale, patients were significantly worse with gluten within 1 week for overall symptoms (P=0.047), pain (P=0.016), bloating (P=0.031), satisfaction with stool consistency (P=0.024), and tiredness (P=0.001). Anti-gliadin antibodies were not induced. There were no significant changes in fecal lactoferrin, levels of celiac antibodies, highly sensitive C-reactive protein, or intestinal permeability. There were no differences in any end point in individuals with or without DQ2/DQ8. "Non-celiac gluten intolerance" may exist, but no clues to the mechanism were elucidated.