CLINICAL EXPERIMENT OF HELICOBACTER PYLORI TRANSMISSION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypotheses: 1. Helicobacter pylori infection (H. pylori), by decreasing gastric acidity, is permissive of gastrointestinal infection with acid-sensitive organisms. 2. Gastrointestinal infection which leads to diarrhea and vomiting increases shedding of H. pylori. Goals: H. pylori causes an extremely common human infection that has persisted since ancient times. In many populations of the world, it is difficult to find uninfected adults. To attain hyperendemic prevalence, the organism must have effective strategies for transmitting itself from person-to-person. Yet, surprisingly, it has been difficult to discover how this transmission occurs. The principle environmental niche for the organism is the human stomach, so to transmit itself the organism must be excreted through the mouth or the anus. Only recently have viable H. pylori been found consistently and incontrovertibly in stools and saliva, and then only after catharsis and emesis were induced in subjects. From this data, we hypothesized that H. pylori is transmitted during bouts of gastroenteritis and that transmission is unusual outside of this setting. Here we postulate that H. pylori transmission is enhanced by its effects on the host's stomach, specifically, its ability to induce hypochlorhydria. H. pylori typically infects humans for the entirety of their lives. To persist in the population then, these chronic infections do not need to be transmitted frequently or continuously; they just need sporadic windows of opportunity. For H. pylori, we believe these windows occur during episodes of diarrhea and vomiting and that H. pylori fosters the occurrence of these events by causing decreased gastric acidity. Acid-resistant and genetically related, acid-sensitive strains of E. coli strains exist that allow us to evaluate gastric conditions permissive of these organisms' entry into the lower gastrointestinal tract, and to test our hypotheses directly in humans. In the end, we hope the results of these human experiments may be useful in preventing both H. pylori infection and some of the diarrheal diseases that exact such a heavy toll from the developing world's children. Endpoints: The aims of this study are to learn: - whether infection with H. pylori increases the risk and/or severity of gastroenteritis caused by an acid-sensitive pathogen: enteropathogenic E. coli (EPEC), - whether this effect is mediated by hypochlorhydria, and - whether infectious gastroenteritis increases shedding of H. pylori in stools and/or vomitus.