title: 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.
abstract: BACKGROUND
  Long-term acid suppression may accelerate the development of atrophic gastritis in Helicobacter pylori-positive subjects. The pathogenetic mechanism remains unclear.
  
  
  OBJECTIVE
  To test the hypothesis that gastric double infection with H. pylori and non-H. pylori bacterial species-during acid suppression-may result in an enhanced inflammatory response, contributing to the development of atrophic gastritis.
  
  
  METHODS
  A consecutive series of patients with gastro-oesophageal reflux disease undergoing treatment with proton pump inhibitors (n=113) or histamine2-receptor antagonists (H2-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 circulating interleukin (IL)-1beta, IL-6, and IL-8 were examined.
  
  
  RESULTS
  Patients on acid suppression with either proton pump inhibitors or H2-RAs had a similar prevalence of H. pylori infection to the controls, but 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 bacteria 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 presence of H. pylori and non-H. pylori bacteria was associated with a markedly increased risk of atrophic gastritis (antrum: RR, 20.25; corpus: RR, 20.38), compatible with a synergistic effect. Furthermore, the simultaneous presence of both types of bacteria was associated with higher cytokine levels than in patients without any type of bacteria. This increase was also greater than in patients with H. pylori infection alone (P < 0.001, for both IL-1beta and IL-8).
  
  
  CONCLUSIONS
  H. pylori-positive patients on long-term acid inhibition displayed three features: non-H. pylori bacterial growth; increased cytokine levels; and a higher risk of atrophic gastritis. We suggest that double infection with H. pylori and non-H. pylori bacteria is a major factor in the development of atrophic gastritis during gastric acid inhibition.
authors.affiliation: Department of Gastroenterology/Hepatology, University Hospital Maastricht, The Netherlands. sda@sint.azm.nl
authors.forename: S
authors.initials: S
authors.lastname: Sanduleanu
authors.forename: D
authors.initials: D
authors.lastname: Jonkers
authors.forename: A
authors.initials: A
authors.lastname: De Bruïne
authors.forename: W
authors.initials: W
authors.lastname: Hameeteman
authors.forename: R W
authors.initials: RW
authors.lastname: Stockbrügger
mesh_terms: D000328:Adult; D000368:Aged; D000863:Antacids / Q000009:adverse effects* / Q000627:therapeutic use; D002908:Chronic Disease; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005757:Gastritis, Atrophic / Q000139:chemically induced / Q000209:etiology*; D005764:Gastroesophageal Reflux / Q000150:complications* / Q000188:drug therapy; D016481:Helicobacter Infections / Q000139:chemically induced / Q000175:diagnosis / Q000209:etiology* / Q000382:microbiology; D016480:Helicobacter pylori / Q000302:isolation & purification / Q000472:pathogenicity; D006633:Histamine Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007378:Interleukins / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000166:cytology / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D054328:Proton Pump Inhibitors; D017494:Proton Pumps / Q000627:therapeutic use; D011706:Pyloric Antrum; D012307:Risk Factors; D013270:Stomach / Q000382:microbiology
chemical_list: D000863:Antacids; D016207:Cytokines; D006633:Histamine Antagonists; D007378:Interleukins; D054328:Proton Pump Inhibitors; D017494:Proton Pumps