CLINICAL EXPERIMENT OF HELICOBACTER PYLORI TRANSMISSION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。假设:1。幽门螺杆菌感染（H. pylori），通过降低胃酸，允许胃酸敏感的微生物感染胃肠道。2. 导致腹泻和呕吐的胃肠道感染会增加幽门螺杆菌的排出。目标：幽门螺旋杆菌是一种非常常见的人类感染，自古以来就一直存在。在世界许多人口中，很难找到未受感染的成年人。要实现高地方性流行，生物体必须具有有效的人际传播策略。然而，令人惊讶的是，很难发现这种传播是如何发生的。这种生物的主要生存环境是人的胃，所以为了传播它自己，这种生物必须通过嘴或肛门排出体外。直到最近才在粪便和唾液中持续且无可争议地发现了可存活的幽门螺杆菌，而且只有在受试者进行了泻泻和呕吐后才发现。根据这些数据，我们假设幽门螺杆菌是在肠胃炎发作期间传播的，在这种情况下传播是不寻常的。在这里，我们假设幽门螺杆菌的传播通过其对宿主胃的影响而增强，特别是其诱导低氯酸的能力。幽门螺旋杆菌通常会在人的一生中感染。为了在人群中持续存在，这些慢性感染不需要频繁或持续传播；他们只是需要零星的机会。对于幽门螺杆菌，我们认为这些窗口期发生在腹泻和呕吐期间，幽门螺杆菌通过降低胃酸来促进这些事件的发生。耐酸和基因相关的酸敏感型大肠杆菌菌株的存在，使我们能够评估允许这些有机体进入下胃肠道的胃条件，并直接在人体中测试我们的假设。最后，我们希望这些人体实验的结果可能有助于预防幽门螺杆菌感染和一些腹泻疾病，这些疾病对发展中国家的儿童造成了巨大的伤害。终点：本研究的目的是了解：-幽门螺杆菌感染是否会增加由酸敏感病原体肠致病性大肠杆菌（EPEC）引起的胃肠炎的风险和/或严重程度，-这种影响是否由次氯酸介导，-感染性胃肠炎是否会增加粪便和/或呕吐物中幽门螺杆菌的脱落。

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.