title: Genetic or chemical hypochlorhydria is associated with inflammation that modulates parietal and G-cell populations in mice.
abstract: OBJECTIVE
  Reduced gastric acid predisposes the stomach to colonization by bacteria and inflammation. Therefore, we investigated how the chronic gastritis in mice made hypochlorhydric by either gastrin deficiency or omeprazole treatment modulates epithelial cell function.
  
  
  METHODS
  The gastric pathology of 16-week-old wild-type gastrin-expressing (G+/+) and gastrin-deficient (G-/-) mice maintained in conventional housing was compared. G-/- mice were then treated with antibiotics for 20 days. In a separate experiment, G+/+ mice were treated with omeprazole for 2 months or treated with omeprazole and antibiotics.
  
  
  RESULTS
  Compared with the G+/+ animals, the hypochlorhydric G-/- mice showed significant inflammation that resolved after 20 days of antibiotic treatment and correlated with a decrease in bacterial overgrowth. Elevated G- and parietal-cell numbers in the G-/- mice, quantified by flow cytometry, normalized after antibiotic treatment. G+/+ mice treated with omeprazole had increased bacteria and mucosal lymphocytes that resolved after antibiotic therapy. Quantitation of the gastric cells in these omeprazole-treated mice revealed a significant increase in G- and parietal-cell numbers. On resolution of the gastritis, a decrease in parietal and gastrin-expressing (G) cells was observed despite sustained hypochlorhydria in the presence of omeprazole.
  
  
  CONCLUSIONS
  Genetic or chemical hypochlorhydria predisposes the stomach to bacterial overgrowth resulting in inflammation. The specific changes in parietal and G cells correlate with the presence of inflammation and not directly with gastric acid. Thus, the normal stomach responds to inflammation by increasing the number and function of cell types that are able to maximize gastric acid output.
authors.affiliation: Howard Hughes Medical Institute, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Yana
authors.initials: Y
authors.lastname: Zavros
authors.forename: Gabriele
authors.initials: G
authors.lastname: Rieder
authors.forename: Amy
authors.initials: A
authors.lastname: Ferguson
authors.forename: Linda C
authors.initials: LC
authors.lastname: Samuelson
authors.forename: Juanita L
authors.initials: JL
authors.lastname: Merchant
mesh_terms: D000126:Achlorhydria / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000897:Anti-Ulcer Agents; D001402:B-Lymphocytes / Q000166:cytology; D001431:Bacteriological Techniques; D002167:Campylobacter / Q000254:growth & development; D002169:Campylobacter Infections / Q000188:drug therapy / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005744:Gastric Acid / Q000378:metabolism; D005755:Gastrins / Q000235:genetics*; D005756:Gastritis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000188:drug therapy / Q000473:pathology; D016480:Helicobacter pylori / Q000254:growth & development; D008297:Male; D051379:Mice; D009853:Omeprazole; D010295:Parietal Cells, Gastric / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000166:cytology
chemical_list: D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D005755:Gastrins; D009853:Omeprazole