title: Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebo-controlled trial.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  "Non-celiac gluten intolerance" may exist, but no clues to the mechanism were elucidated.
authors.affiliation: Monash University Department of Medicine and Gastroenterology, Box Hill Hospital, Box Hill, Victoria, Australia.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Biesiekierski
authors.forename: Evan D
authors.initials: ED
authors.lastname: Newnham
authors.forename: Peter M
authors.initials: PM
authors.lastname: Irving
authors.forename: Jacqueline S
authors.initials: JS
authors.lastname: Barrett
authors.forename: Melissa
authors.initials: M
authors.lastname: Haines
authors.forename: James D
authors.initials: JD
authors.lastname: Doecke
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Shepherd
authors.forename: Jane G
authors.initials: JG
authors.lastname: Muir
authors.forename: Peter R
authors.initials: PR
authors.lastname: Gibson
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002446:Celiac Disease / Q000175:diagnosis; D003092:Colitis / Q000139:chemically induced; D055050:Diet, Gluten-Free; D004311:Double-Blind Method; D004751:Enteritis / Q000139:chemically induced; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology*; D005983:Glutens / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000276:immunology / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005983:Glutens