Ans Pauwels1, Charlotte Broers1, Tim Vanuytsel1, Nicolas Pardon1, Silvia Cocca2, Sabine Roman3, Frank Zerbib4, Jan Tack1, Ricard Farré1,5. 1. Catholic University of Leuven, KU Leuven, Translational Research Center for Gastrointestinal Disorders (TARGID), Leuven, Belgium. 2. 2Department of Digestive Diseases, Campus Bio-Medico University, Rome, Italy. 3. Digestive Physiology, Hospices Civils de Lyon and Lyon I University; and LabTAU, Inserm U1032, Lyon, France. 4. Gastroenterology department, Hôpital Haut Lévêque, CHU de Bordeaux; and Université de Bordeaux, Bordeaux, France. 5. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, (Ciberehd), Instituto de Salud Carlos III, Barcelona, Spain.
Abstract
INTRODUCTION: Approximately 30% of healthy volunteers (HVs) show dilated intercellular spaces in the esophageal epithelium suggesting a functionally reduced epithelial integrity. We aimed to evaluate the presence of an altered epithelial integrity in HVs and whether physiological acid could explain such a difference. METHODS: Biopsies for Ussing chamber experiments were taken between 3 cm and 5 cm proximal to the gastroesophageal junction. Twenty-four-hour impedance-pH (MII-pH) monitoring was performed in the same 15 HVs. MII-pH tracings from 24 HVs before and after treatment with esomeprazole (40 mg b.i.d., two weeks), a proton pump inhibitor, were analyzed. Reflux parameters and impedance baseline (IB) at different levels of the esophagus were calculated. RESULTS: Epithelial integrity in the distal esophagus presents a large variability in vivo and in vitro (transepithelial electrical resistance 196.9 ± 16.27Ω. cm2; IB measurements 2022 ± 143.5Ω). Esomeprazole highly suppressed the total acid exposure time (AET) (1.9 (0.8-3.1) vs 0 (0-0)%, p < 0.0001). After splitting our participants into "high" and "low" IB, based on the median value, we observed only in the distal esophagus a higher total AET before (2.8 (1.6-4.8) vs 1.0 (0.5-2.2), p = 0.04) and increased IB values after esomeprazole (1620 (1347-1898) vs 2192 (1784-2503)Ω, p = 0.002) in the "low" IB group. CONCLUSION: A subgroup of HVs presents a low epithelial integrity in the distal esophagus probably due to the increased presence of physiological acid reflux. Whether these individuals have a higher chance to develop gastroesophageal reflux disease is unknown. The role of epithelial integrity in symptom perception needs to be further explored.
INTRODUCTION: Approximately 30% of healthy volunteers (HVs) show dilated intercellular spaces in the esophageal epithelium suggesting a functionally reduced epithelial integrity. We aimed to evaluate the presence of an altered epithelial integrity in HVs and whether physiological acid could explain such a difference. METHODS: Biopsies for Ussing chamber experiments were taken between 3 cm and 5 cm proximal to the gastroesophageal junction. Twenty-four-hour impedance-pH (MII-pH) monitoring was performed in the same 15 HVs. MII-pH tracings from 24 HVs before and after treatment with esomeprazole (40 mg b.i.d., two weeks), a proton pump inhibitor, were analyzed. Reflux parameters and impedance baseline (IB) at different levels of the esophagus were calculated. RESULTS: Epithelial integrity in the distal esophagus presents a large variability in vivo and in vitro (transepithelial electrical resistance 196.9 ± 16.27Ω. cm2; IB measurements 2022 ± 143.5Ω). Esomeprazole highly suppressed the total acid exposure time (AET) (1.9 (0.8-3.1) vs 0 (0-0)%, p < 0.0001). After splitting our participants into "high" and "low" IB, based on the median value, we observed only in the distal esophagus a higher total AET before (2.8 (1.6-4.8) vs 1.0 (0.5-2.2), p = 0.04) and increased IB values after esomeprazole (1620 (1347-1898) vs 2192 (1784-2503)Ω, p = 0.002) in the "low" IB group. CONCLUSION: A subgroup of HVs presents a low epithelial integrity in the distal esophagus probably due to the increased presence of physiological acid reflux. Whether these individuals have a higher chance to develop gastroesophageal reflux disease is unknown. The role of epithelial integrity in symptom perception needs to be further explored.
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