Oesophageal mucosal barrier: a key factor in the pathophysiology of non-erosive reflux disease (NERD) and a potential target for treatment
- Center for Digestive Diseases, Wingate Institute for Neurogastroenterology, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
- Correspondence to Dr Daniel Sifrim, Wingate Institute of Neurogastroenterology, 26 Ashfield Street, London E1 2AJ, UK;
- Received 3 June 2013
- Revised 16 June 2013
- Accepted 18 June 2013
- Published Online First 6 July 2013
The stratified squamous epithelium of the oesophageal mucosa usually forms a tight protective barrier against noxious components of gastro-oesophageal reflux (such as acid and bile acids), a necessary function since the distal oesophageal mucosa is exposed to physiological reflux events, even in health.
If there is a disruption to the effectiveness of this epithelial barrier (a so-called impairment of the mucosal integrity), its protective function is likely to be compromised, resulting in reflux-induced symptoms.
Non-erosive reflux disease (NERD) is the phenotype of gastro-oesophageal reflux disease most frequently encountered in clinical practice, and may be more difficult to treat than erosive reflux disease.1 Contrary to endoscopic appearances, the oesophageal mucosa in patients with NERD is not completely normal and integrity of the mucosal barrier is impaired. This has been demonstrated by morphological and functional studies. In NERD, the basal layer of oesophageal mucosal epithelium demonstrates dilated intercellular spaces (DIS).2 This histological abnormality is not specific for NERD but is related to mucosal exposure to intraluminal acid since it resolves with successful proton pump inhibitors (PPI) therapy.3
Functional studies confirm impairment of oesophageal mucosal integrity in NERD. These studies have been performed both in vitro, in biopsies of NERD patients, and in vivo, by measuring oesophageal baseline impedance.
Measurements of trans-epithelial electrical resistance (TEER) (a measure of paracellular permeability to ions), either in tissue sections or in biopsies, are used to interrogate the oesophageal mucosal barrier function. When the mucosa is exposed to solutions containing acid and bile acids, the TEER falls and the magnitude of such reduction correlates with permeability to small molecules (such …