CLINICAL EXPERIMENT OF HELICOBACTER PYLORI TRANSMISSION

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。假设：1.幽门螺杆菌感染（H. pylori）通过降低胃酸度，允许酸敏感生物体的胃肠道感染。2.胃肠道感染可导致腹泻和呕吐，从而增加H。幽门。 目标：H.幽门螺杆菌是一种极为常见的人类感染，自古以来就一直存在。在世界上许多人口中，很难找到未受感染的成年人。为了达到高流行病的流行，生物体必须有有效的策略，在人与人之间传播。然而，令人惊讶的是，很难发现这种传播是如何发生的。该生物体的主要环境生态位是人类的胃，因此为了传播自身，该生物体必须通过口腔或肛门排泄。直到最近才有活的H。幽门螺杆菌在粪便和唾液中一致且无可争议地被发现，然后仅在受试者被诱导导泻和呕吐后才被发现。根据这些数据，我们假设H。幽门螺旋杆菌在肠胃炎发作时传播，在肠胃炎以外的地方传播是不寻常的。这里我们假设H.幽门螺旋杆菌的传播通过其对宿主胃的作用而增强，特别是其诱导低氯血症的能力。 H.幽门螺杆菌通常感染人的整个生命。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;它们只需要零星的机会之窗。螺杆pylori感染时，我们认为这些窗口期出现在腹泻和呕吐的发作期，幽门螺杆菌通过引起胃酸度降低而促进这些事件的发生。耐酸性和遗传相关的酸敏感菌株的E。大肠杆菌菌株的存在，使我们能够评估胃的条件允许这些生物体进入下胃肠道，并直接在人类中测试我们的假设。最后，我们希望这些人体实验的结果可能有助于预防H。幽门螺杆菌感染和一些导致发展中国家儿童死亡人数如此之多的慢性疾病。 目的：本研究的目的是了解：-是否感染H。幽门螺杆菌增加了由酸敏感病原体引起的胃肠炎的风险和/或严重程度：肠致病性E.大肠杆菌（EPEC），-这种作用是否是介导的次氯酸钠，和-是否感染性胃肠炎增加脱落的H。粪便和/或呕吐物中的幽门螺杆菌。

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.