title: Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome.
abstract: OBJECTIVE
  We investigated suspected food intolerances in patients with irritable bowel syndrome (IBS) using confocal laser endomicroscopy (CLE) for real-time visualization of structural/functional changes in the intestinal mucosa after food challenge. Patients with functional changes after food challenge (CLE+) were placed on personalized exclusion diets and followed up for long-term symptom relief.
  
  
  METHODS
  Thirty-six IBS patients with suspected food intolerance and 10 patients with Barrett's esophagus (controls) without IBS symptoms were examined by CLE at University Hospital Schleswig-Holstein (Kiel, Germany). Diluted food antigens were administered directly to the duodenal mucosa through the working channel of the endoscope. Epithelial breaks, intervillous spaces, and the number of intraepithelial lymphocytes (IEL) were measured before and after the food challenge. CLE+ patients were placed on exclusion diets, given symptom score questionnaires, and followed up for 1 year; controls resumed their previous diet.
  
  
  RESULTS
  CLE showed a real-time response to food antigens in 22 of 36 patients; no responses were observed in 14 of 36 patients (CLE-) or any of the controls. Baseline IELs were significantly higher in CLE+ than CLE- subjects (P = .004); numbers increased significantly after food challenge (P = .0008). Within 5 minutes of exposure of CLE+ patients to food antigens, IELs increased, epithelial leaks/gaps formed, and intervillous spaces widened. Epithelial leaks and intervillous spaces also increased significantly in CLE+ vs baseline (both P < .001). The concordance of IELs measured by CLE and conventional histology was 70.6%; they did not correlate (P = .89; r(2) = 0.027). Symptom scores improved more than 50% in CLE+ patients after a 4-week exclusion diet and increased to 74% at 12 months; symptoms continued in CLE- patients.
  
  
  CONCLUSIONS
  Based on CLE analysis of IBS patients with a suspected food intolerance, exposure to candidate food antigens caused immediate breaks, increased intervillous spaces, and increased IELs in the intestinal mucosa. These changes are associated with patient responses to exclusion diets. Registered at clinicaltrials.gov (registration number: NCT01692613).
authors.affiliation: Unit of Experimental Endoscopy, Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany. Electronic address: fri.rav@btopenworld.com.
authors.forename: Annette
authors.initials: A
authors.lastname: Fritscher-Ravens
authors.affiliation: Institute of Translational Immunology, Department of Medicine I, University of Mainz, Mainz, Germany; Research Center for Immunology, University of Mainz, Mainz, Germany; Division of Gastroenterology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts.
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
authors.affiliation: Unit of Experimental Endoscopy, Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Ellrichmann
authors.affiliation: Unit of Experimental Endoscopy, Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schoch
authors.affiliation: Department of Pathology, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
authors.affiliation: Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Brasch
authors.affiliation: Unit of Experimental Endoscopy, Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Bethge
authors.affiliation: Department of Anatomy, Christian Albrecht University, Kiel, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Böttner
authors.affiliation: Unit of Experimental Endoscopy, Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Julius
authors.initials: J
authors.lastname: Klose
authors.affiliation: University College London Institute of Child Health, University College London, London, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Milla
mesh_terms: D000328:Adult; D000368:Aged; D004386:Duodenum / Q000276:immunology / Q000473:pathology*; D016099:Endoscopy, Gastrointestinal / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D005502:Food / Q000009:adverse effects*; D005512:Food Hypersensitivity / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D007159:Immunologic Tests; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology*; D043183:Irritable Bowel Syndrome / Q000175:diagnosis* / Q000178:diet therapy / Q000276:immunology / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods*; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
keywords: FODMAP; Food Allergy; Gluten; Imaging