Helicobacter pylori commonly infects the stomach, where it causes inflammation (gastritis) in all individuals and peptic ulcer disease or gastric cancer in some. The best studied bacterial factor associated with development of gastric cancer and peptic ulcer is the cag pathogenicity island (cag PAI). We recently used the rhesus macaque model to demonstrate that H. pylori induces an antimicrobial host response in a cag PAI-dependent manner, which includes upregulation of 2- defensin2, elafin, siderocalin, and other innate immune effector molecules in the gastric mucosa. At first glance it seems paradoxical that H. pylori has horizontally acquired a PAI that serves, at least in part, to induce an antimicrobial innate immune response. One possibility is that these antimicrobial proteins may be inactive against H. pylori, or at least less active than against other microbiota that compete for the same gastric niche. While previously viewed as sterile except for H. pylori, recent evidence based on broad range 16S rDNA libraries suggests that the microbiota of the human stomach has considerable diversity. H. pylori bearing the cag PAI may induce an antimicrobial response that is active against some of these organisms, and so may help H. pylori compete effectively. We hypothesize that H. pylori induces an innate antimicrobial host response in a cag PAI dependent manner, which alters the gastric microbial community and increases the competitive advantage of H. pylori in the gastric niche. Here we propose to examine the effects of H. pylori on the gastric microbial community, and in turn to study the effect that this community has on H. pylori colonization. Since cag PAI-dependent changes in the gastric microbiota, or even the microbiota of the gut, could be important in the diverse outcomes that occur after infection with H. pylori, this work fits squarely within the human microbiome initiative that was recently incorporated into the NIH Roadmap.

Public Health Relevance

Helicobacter pylori is an important gastric pathogen that induces an innate antimicrobial host response in the gastric epithelium. We hypothesize that this antimicrobial response alters the gastric microbial community and increases the competitive advantage of H. pylori in the gastric niche.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI080788-02
Application #
7843477
Study Section
Gastrointestinal Mucosal Pathobiology Study Section (GMPB)
Program Officer
Mills, Melody
Project Start
2009-05-15
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2012-04-30
Support Year
2
Fiscal Year
2010
Total Cost
$191,250
Indirect Cost
Name
University of California Davis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Martin, Miriam E; Solnick, Jay V (2014) The gastric microbial community, Helicobacter pylori colonization, and disease. Gut Microbes 5:345-50
Martin, Miriam E; Bhatnagar, Srijak; George, Michael D et al. (2013) The impact of Helicobacter pylori infection on the gastric microbiota of the rhesus macaque. PLoS One 8:e76375