J Neurogastroenterol Motil.  2017 Oct;23(4):517-525. 10.5056/jnm16178.

Relationship Between Salivary Pepsin Concentration and Esophageal Mucosal Integrity in Patients With Gastroesophageal Reflux Disease

  • 1Department of Gastroenterology, First affiliated Hospital, Sun Yat-sen University, Guangzhou, GuangDong Province, China. chenminhu@vip.163.com
  • 2Wingate Institute of Neurogastroenterology, Queen Mary University of London, London, UK.


Increased salivary pepsin could indicate an increase in gastro-esophageal reflux, however, previous studies failed to demonstrate a correlation between salivary pepsin concentrations and 24-hour esophageal acid exposure. This study aims to detect the salivary pepsin and to evaluate the relationship between salivary pepsin concentrations and intercellular spaces (IS) in different gastroesophageal reflux disease phenotypes in patients.
A total of 45 patients and 11 healthy volunteers were included in this study. All subjects underwent upper gastrointestinal endoscopy, 24-hour ambulatory multichannel impedance-pH (MII-pH) monitoring, and salivary sampling at 3-time points during the 24-hour MII-pH monitoring. IS were measured by transmission electron microscopy, and salivary pepsin concentrations were determined by enzyme-linked immunosorbent assay.
The IS measurements were greater in the esophagitis (EE), non-erosive reflux disease (NERD), and hypersensitive esophagus (HO) groups than in the functional heartburn (FH) and healthy volunteer groups, and significant differences were indicated. Patients with NERD and HO had higher average pepsin concentrations compared with FH patients. A weak correlation was determined between IS and salivary pepsin among patients with NERD (r = 0.669, P = 0.035).
We confirmed the presence of a higher level of salivary pepsin in patients with NERD than in patients with FH. Salivary pepsin concentrations correlated with severity of mucosal integrity impairment in the NERD group. We suggest that in patients with NERD, low levels of salivary pepsin can help identify patients with FH, in addition the higher the pepsin concentration, the more likely the severity of dilated IS.


Acid exposure time; Dilated intercellular spaces; Gastroesophageal reflux disease; Salivary pepsin

MeSH Terms

Endoscopy, Gastrointestinal
Enzyme-Linked Immunosorbent Assay
Extracellular Space
Gastroesophageal Reflux*
Healthy Volunteers
Microscopy, Electron, Transmission
Pepsin A*
Pepsin A
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