Helicobacter pylori and the gastric microbial community in rhesus macaques

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DESCRIPTION (provided by applicant): 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.