The long-term objective underlying the research proposed within this exploratory R21 application is to understand how host inflammation associated with the chronic human pathogen, Helicobacter pylori (Hp), fully impacts human health and disease. The persistent inflammation localized within the gastric mucosa during chronic Hp infection is considered the major risk factor for the onset of gastric diseases, including gastric ulcer disease and gastric adenocarcinoma. However, persistent low-level systemic inflammation also accompanies Hp gastric infection, which has been increasingly associated with extra-gastric diseases. The major gap in knowledge to be addressed in this application is the extent to which neuroinflammation, which is synonymous with brain inflammation, accompanies chronic gastric infection with Hp. In vivo animal infection studies, using Sprague-Dawley rats as an established model for studying cognitive performance, will be conducted to evaluate the previously unexplored hypothesis that chronic gastric infection with Hp promotes neuroinflammation. Preliminary results support this hypothesis, by revealing that elevated brain inflammation accompanies short-term gastric infection with Hp. Here, we propose studies to extend the duration of Hp infection to study both systemic and neuroinflammation under conditions that more closely recapitulate chronic infection. To understand the underlying mediators of systemic and neuroinflammation, levels of innate immune inflammatory cytokines normally associated with Hp gastric infection will be monitored. Finally, the causal relationship between Hp infection and neuroinflammation will be explored by monitoring neuroinflammation in the brains of animals whose Hp infections were eradicated by antibiotic administration. Results from the studies proposed here will not only advance our understanding of the extra-gastric effects of chronic Hp infection, but will also provide the necessary experimental framework for future collaborative studies to investigate the impact of neuroinflammation on the cognitive performance of animals chronically infected with Hp.
Chronic infection with the human pathogen, Helicobacter pylori, is a major risk factor for several important diseases, including stomach cancer. In this application, we propose animal studies to evaluate the manner in which the inflammation that accompanies chronic Helicobacter pylori infection negatively impacts functions associated with central nervous system and brain, such as learning and memory. Understanding the full spectrum of diseases associated with Helicobacter pylori infection will improve clinical decisions about how to most effectively treat infected individuals.
