title: Efficacy of a Gluten-Free Diet in Subjects With Irritable Bowel Syndrome-Diarrhea Unaware of Their HLA-DQ2/8 Genotype.
abstract: OBJECTIVE
  A gluten-containing diet alters bowel barrier function in patients with irritable bowel syndrome with diarrhea (IBS-D), particularly those who are positive for HLA allele DQ2/8. We studied the effects of a gluten-free diet (GFD) in patients with IBS-D who have not previously considered the effects of gluten in their diet and were unaware of their HLA-DQ2/8 genotype.
  
  
  METHODS
  We performed a prospective study of 41 patients with IBS-D (20 HLA-DQ2/8-positive and 21 HLA-DQ2/8-negative) at the Royal Hallamshire Hospital in Sheffield, United Kingdom, from September 2012 through July 2015. All subjects were placed on a 6-week GFD following evaluation by a dietician. Subjects completed validated questionnaires at baseline and Week 6 of the GFD. The primary endpoint was mean change in IBS Symptom Severity Score; a 50-point reduction was considered to indicate a clinical response. Secondary endpoints were changes in hospital anxiety and depression score, fatigue impact score, and Short Form-36 results. Clinical responders who chose to continue a GFD after the study period were evaluated on average 18 months later to assess diet durability, symptom scores, and anthropometric and biochemical status.
  
  
  RESULTS
  A 6-week GFD reduced IBS Symptom Severity Score by ≥50 points in 29 patients overall (71%). The mean total IBS Symptom Severity Score decreased from 286 before the diet to 131 points after 6 weeks on the diet (P < .001); the reduction was similar in each HLA-DQ group. However, HLA-DQ2/8-negative subjects had a greater reduction in abdominal distention (P = .04). Both groups had marked mean improvements in hospital anxiety and depression scores, fatigue impact score, and Short Form-36 results, although HLA-DQ2/8-positive subjects had a greater reduction in depression score and increase in vitality score than HLA-DQ2/8-negative subjects (P = .02 and P = .03, respectively). Twenty-one of the 29 subjects with a clinical response (72%) planned to continue the GFD long term; 18 months after the study they were still on a GFD, with maintained symptom reductions, and demonstrated similar anthropometric and biochemical features compared with baseline.
  
  
  CONCLUSIONS
  A dietitian-led GFD provided sustained benefit to patients with IBS-D. The symptoms that improved differed in magnitude according to HLA-DQ status. Clinical trials.gov no: NCT02528929.
authors.affiliation: Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, United Kingdom. Electronic address: imran.aziz@sth.nhs.uk.
authors.forename: Imran
authors.initials: I
authors.lastname: Aziz
authors.affiliation: Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, United Kingdom.
authors.forename: Nick
authors.initials: N
authors.lastname: Trott
authors.affiliation: Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, United Kingdom.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Briggs
authors.affiliation: Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, United Kingdom.
authors.forename: John R
authors.initials: JR
authors.lastname: North
authors.affiliation: Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, United Kingdom.
authors.forename: Marios
authors.initials: M
authors.lastname: Hadjivassiliou
authors.affiliation: Academic Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield Teaching Hospitals, Sheffield, United Kingdom.
authors.forename: David S
authors.initials: DS
authors.lastname: Sanders
mesh_terms: D000328:Adult; D003967:Diarrhea / Q000628:therapy*; D055050:Diet, Gluten-Free; D005260:Female; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016896:Treatment Outcome; D006113:United Kingdom
chemical_list: D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen
keywords: Carbohydrates; Clinical Trial; Food; Gastrointestinal Symptoms