Double gastric infection with Helicobacter pylori and non-Helicobacter pylori bacteria during acid-suppressive therapy: increase of pro-inflammatory cytokines and development of atrophic gastritis

Background: Long-term acid suppression may accelerate the development of at rophic gastritis in Helicobacter pylori-positive subjects. The pathogenetic mechanism remains unclear. Aim: To test the hypothesis that gastric double infection with H. pylori an d non-H. pylori bacterial species-during acid suppression-may result in an enhanced inflammatory response, contributing to the development of atrophic gastritis. Patients and methods: A consecutive series of patients with gastro-oesophag eal reflux disease undergoing treatment with proton pump inhibitors (n=113) or histamine(2)-receptor antagonists (H-2-RAs) (n=37), and 76 non-treated dyspeptic controls were investigated. Gastric mucosal H. pylori and non-H. pylori bacteria, histological gastritis, H. pylori serology, and circulatin g interleukin (IL)-1 beta, IL-6, and IL-8 were examined. Results: Patients on acid suppression with either proton pump inhibitors or H-2-RAs had a similar prevalence of H. pylori infection to the controls, b ut a higher prevalence of non-H. pylori bacteria (61% and 60% vs. 29%, P < 0.0001 and P < 0.002). Both the presence of H. pylori and non-H. pylori bac teria were independent risk factors of atrophic gastritis (antrum: relative risks (RRs), 10.1 and 5.07; corpus: RRs, 11.74 and 6.38). A simultaneous p resence of H. pylori and non-H. pylori bacteria was associated with a marke dly increased risk of atrophic gastritis (antrum: RR, 20.25; corpus: RR, 20 .38), compatible with a synergistic effect. Furthermore, the simultaneous p resence of both types of bacteria was associated with higher cytokine level s than in patients without any type of bacteria. This increase was also gre ater than in patients with H. pylori infection alone (P < 0.001, for both I L-1 beta and IL-8). Summary and conclusions: H. pylori-positive patients on long-term acid inhi bition displayed three features: non-H. pylori bacterial growth; increased cytokine levels; and a higher risk of atrophic gastritis. We suggest that d ouble infection with H. pylori and non-H. pyloribacteria is a major factor in the development of atrophic gastritis during gastric acid inhibition.