Annette Fritscher-Ravens1, Detlef Schuppan2, Mark Ellrichmann3, Stefan Schoch3, Christoph Röcken4, Jochen Brasch5, Johannes Bethge3, Martina Böttner6, Julius Klose3, Peter J Milla7. 1. Unit of Experimental Endoscopy, Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany. Electronic address: fri.rav@btopenworld.com. 2. 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. 3. Unit of Experimental Endoscopy, Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel, Germany. 4. Department of Pathology, University Hospital Schleswig-Holstein, Kiel, Germany. 5. Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany. 6. Department of Anatomy, Christian Albrecht University, Kiel, Germany. 7. University College London Institute of Child Health, University College London, London, United Kingdom.
Abstract
BACKGROUND & AIMS: 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).
BACKGROUND & AIMS: 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 IBSpatients 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 IBSpatients 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).
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