Exploration of the Esophageal Mucosal Barrier in Non-Erosive Reflux Disease

Abstract

In the absence of visible mucosal damage, it is hypothesized that the esophageal mucosal barrier is functionally impaired in patients with non-erosive reflux disease (NERD). The aim of the present study was to perform an exploratory analysis of the mucosal barrier in NERD compared to erosive esophagitis (EE) and controls. A second aim was to explore TRPV1 gene transcription in relation to the mucosal barrier function and heartburn symptoms. In this prospective study, 10 NERD patients, 11 patients with active erosive esophagitis and 10 healthy volunteers were included. Biopsies from non-eroded mucosa were obtained for (1) ex vivo analyses (Ussing chamber) of transepithelial electrical resistance (TEER) and permeability (2) gene transcription of tight-junction proteins and transient receptor potential vanilloid subfamily member 1 (TRPV1). No differences in TEER or permeability were found between NERD and healthy volunteers, whereas TEER was lower in patients with erosive esophagitis. TRPV1 gene transcription was not significantly different between EE, NERD and controls. Conclusions: esophageal mucosal barrier function and TRPV1 transcription is not significantly altered in NERD patients. Future research is needed to explore other potential mechanisms that may account for the high symptom burden in these patients.

Intestinal barrier function is maintained with aging – a comprehensive study in healthy subjects and irritable bowel syndrome patients

“…Six tissue samples from the sigmoid colon were used for ex vivo Ussing chamber experiments as previously described by our group 25 . Three tissue samples were stressed by adding mast cell degranulator Compound 48/80 (1 µg/ml, Sigma-Aldrich, St. Louis, MO, USA) to the serosal compartment.…”

Role of TRPV1 receptor in inflammation and impairment of esophageal mucosal integrity in a murine model of nonerosive reflux disease

“…Third, the size of the sample evaluated in an Ussing chamber is much smaller. 33,34 The present results provide new insights into NERD pathophysiology. We demonstrated that TRPV1 is critical for the esophageal inflammatory response and impairment of esophageal mucosal integrity.…”

“…The alteration of epithelial barrier function is well elucidated in patients with EE, but is controversial in patients with NERD . In contrast with studies measuring in vivo impedance, the ex vivo evaluation of biopsies from esophageal mucosa in an Ussing chamber system revealed no difference in basal TEER between patients with NERD and controls . Some factors may explain, at least in part, this discrepancy.…”

“…Second, mediators released from sensory nerve endings and immune cells may be present in the mucosa in vivo, but not in the epithelium ex vivo. Third, the size of the sample evaluated in an Ussing chamber is much smaller …”

“…32,33 In contrast with studies measuring in vivo impedance, the ex vivo evaluation of biopsies from esophageal mucosa in an Ussing chamber system revealed no difference in basal TEER between patients with NERD and controls. 32,34 Some factors may explain, at least in part, this discrepancy. First, endogenous factors (ie, bicarbonate, saliva secretion, and blood flow) may influence mucosal impedance.…”