Genetic or Chemical Hypochlorhydria Is Associated With Inflammation That Modulates Parietal and G-cell Populations in Mice

Gastroenterology. 2002 Jan;122(1):119-33. doi: 10.1053/gast.2002.30298.

Abstract

Background & aims: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Achlorhydria / chemically induced
  • Achlorhydria / immunology*
  • Achlorhydria / microbiology*
  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Anti-Ulcer Agents
  • B-Lymphocytes / cytology
  • Bacteriological Techniques
  • Campylobacter / growth & development
  • Campylobacter Infections / drug therapy
  • Campylobacter Infections / pathology
  • Female
  • Flow Cytometry
  • Gastric Acid / metabolism
  • Gastrins / genetics*
  • Gastritis / immunology*
  • Gastritis / microbiology
  • Gastritis / pathology
  • Helicobacter Infections / drug therapy
  • Helicobacter Infections / pathology
  • Helicobacter pylori / growth & development
  • Male
  • Mice
  • Omeprazole
  • Parietal Cells, Gastric / metabolism
  • Parietal Cells, Gastric / pathology*
  • T-Lymphocytes / cytology

Substances

  • Anti-Bacterial Agents
  • Anti-Ulcer Agents
  • Gastrins
  • Omeprazole