Humans are the only known reservoir of H. pylori infection. How the organism is transmitted from one person to another, however, remains unknown. Data collected during the investigators initial funding period indicate that viable H. pylori are shed by infected hosts in vomitus and diarrheal stools under conditions that simulate gastroenteritis. In addition, H. pylori infection has been linked to increased risk for diarrheal disease, specifically, symptomatic cholera and infantile diarrhea. The investigators postulate that H. pylori decreases gastric acidity, allowing gastroenteritis pathogens to circumvent the first barrier to entry into the intestine. The gastroenteritis pathogens then cause diarrhea and vomiting, fostering excretion of H. pylori and completion of the transmission cycle. With this submission, they propose: 1) to determine whether H. pylori infection, by decreasing gastric acidity, is permissive of gastrointestinal infection with acid sensitive organisms. and 2) to determine whether gastrointestinal infection which leads to diarrhea and vomiting increases shedding of H. pylori.
These aims will be accomplished in a three-pronged fashion: First, they will identify suitable acid-resistant and acid-sensitive strains of non-pathogenic E. coli for human inoculation, and determine the conditions for recovering these organisms from stools. Next, they will administer the acid-resistant/acid-sensitive pair to human subjects and determine the effects of H. pylori infection and gastric acidity on bacterial survival. Last, they will inoculate H. pylori infected and uninfected human subjects with low doses of an acid-sensitive, enteropathogenic E. coli (EPEC) and determine both how H. pylori affects EPEC infectivity and how EPEC affects H. pylori shedding. H. pylori infection causes gastric cancer-the second leading cause of cancer death worldwide-and peptic ulcer disease. Diarrheal disease remains a leading killer of children in developing countries, causing 20 percent of infant mortality worldwide. In these same countries where diarrheal disease runs rampant, H. pylori infects up to 80 percent of the population. If a causal link between these diseases can be established, then treatment or prevention of H. pylori would attain a significantly higher public health priority than it currently occupies.
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