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, 23 (4), 517-525

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


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

Yu-Wen Li et al. J Neurogastroenterol Motil.


Background/aims: 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.

Methods: 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.

Results: 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).

Conclusions: 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.

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

Conflict of interest statement

Conflicts of interest: None.


Figure 1
Figure 1
(A) Comparison of intercellular space among the esophagitis (EE), non-erosive reflux disease (NERD), hypersensitive esophagus (HO), functional heartburn (FH), and healthy volunteer (HV) groups. (B-F) Electron microscope image of EE, NERD, HO, FH, and HV groups. DIS, dilated intercellular spaces.
Figure 2
Figure 2
Salivary pepsin concentration (conc.) in different time points. EE, esophagitis; NERD, non-erosive reflux disease; HO, hypersensitive esophagus; FH, functional heartburn; HV, healthy volunteer. *P < 0.05.
Figure 3
Figure 3
Relationship between salivary pepsin and intercellular spaces (IS) or acid exposure time (AET). (A) IS correlates with salivary pepsin in saliva in all subjects at the time point of before bedtime; (B) IS correlates with AET in all subjects; (C) IS correlates with maximal pepsin concentration (conc.) during the 24-hour monitoring in patients with non-erosive reflux disease (NERD).

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