HELICOBACTER PYLORI AND THE GASTRIC MICROBIAL COMMUNITY IN RHESUS MACAQUES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 幽门螺杆菌通常感染胃，在所有个体中引起炎症（胃炎），在一些个体中引起消化性溃疡疾病或胃癌。研究最多的细菌因素与胃癌和消化性溃疡的发展是cag致病岛（cag派）。我们最近使用恒河猴模型来证明H。幽门螺杆菌以cagPAI依赖性方式诱导抗微生物宿主应答，其包括胃粘膜中2-防御素2、弹性蛋白酶、铁黄素和其它先天免疫效应分子的上调。乍看起来，H。幽门螺杆菌水平获得派，其至少部分用于诱导抗微生物先天免疫应答。一种可能性是这些抗菌蛋白对H.幽门螺杆菌，或至少比竞争相同胃生态位的其他微生物群更不活跃。虽然以前被认为是无菌的，但H。幽门螺杆菌，最近的证据的基础上广泛的16 S rDNA文库表明，人类胃的微生物群具有相当大的多样性。H.携带cag派的pylori可能诱导抗微生物反应，对这些生物体中的一些具有活性，因此可能有助于H. pylori有效竞争。我们假设H. pylori以cag派依赖的方式诱导先天性抗微生物宿主应答，这改变了胃微生物群落并增加了H.胃龛中的幽门。在这里，我们建议检查H的影响。pylori对胃微生物群落的影响，进而研究该群落对H.幽门定植。由于胃微生物群甚至肠道微生物群的cag PAI依赖性变化可能在感染H. pylori，这项工作完全符合最近纳入NIH路线图的人类微生物组计划。公共卫生相关性：幽门螺杆菌是一种重要的胃病原体，可诱导胃上皮细胞产生先天性抗微生物宿主反应。我们推测，这种抗菌反应改变了胃微生物群落，增加了H。胃龛中的幽门。

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. Helicobacter pylori commonly infects the stomach, where it causes inflammation (gastritis) in all individuals and peptic ulcer disease or gastric cancer in some. The best studied bacterial factor associated with development of gastric cancer and peptic ulcer is the cag pathogenicity island (cag PAI). We recently used the rhesus macaque model to demonstrate that H. pylori induces an antimicrobial host response in a cag PAI-dependent manner, which includes upregulation of 2- defensin2, elafin, siderocalin, and other innate immune effector molecules in the gastric mucosa. At first glance it seems paradoxical that H. pylori has horizontally acquired a PAI that serves, at least in part, to induce an antimicrobial innate immune response. One possibility is that these antimicrobial proteins may be inactive against H. pylori, or at least less active than against other microbiota that compete for the same gastric niche. While previously viewed as sterile except for H. pylori, recent evidence based on broad range 16S rDNA libraries suggests that the microbiota of the human stomach has considerable diversity. H. pylori bearing the cag PAI may induce an antimicrobial response that is active against some of these organisms, and so may help H. pylori compete effectively. We hypothesize that H. pylori induces an innate antimicrobial host response in a cag PAI dependent manner, which alters the gastric microbial community and increases the competitive advantage of H. pylori in the gastric niche. Here we propose to examine the effects of H. pylori on the gastric microbial community, and in turn to study the effect that this community has on H. pylori colonization. Since cag PAI-dependent changes in the gastric microbiota, or even the microbiota of the gut, could be important in the diverse outcomes that occur after infection with H. pylori, this work fits squarely within the human microbiome initiative that was recently incorporated into the NIH Roadmap. PUBLIC HEALTH RELEVANCE: Helicobacter pylori is an important gastric pathogen that induces an innate antimicrobial host response in the gastric epithelium. We hypothesize that this antimicrobial response alters the gastric microbial community and increases the competitive advantage of H. pylori in the gastric niche.