HELICOBACTER PYLORI AND THE GASTRIC MICROBIAL COMMUNITY IN RHESUS MACAQUES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 幽门螺杆菌通常会感染胃，在所有人中都会引起炎症(胃炎)，一些人还会患上消化性溃疡或胃癌。研究得最多的与胃癌和消化性溃疡相关的细菌因子是CAG致病岛(CAG PAI)。我们最近使用恒河猴模型证明了幽门螺杆菌以CAG PAI依赖的方式诱导抗菌宿主反应，包括上调胃粘膜中的2-防御素2、弹力素、铁皮环素和其他先天免疫效应分子。乍一看，幽门螺杆菌水平获得了一种PAI，这似乎是自相矛盾的，这种PAI至少在一定程度上是为了诱导抗微生物的先天免疫反应。一种可能性是，这些抗菌蛋白可能对幽门螺杆菌没有活性，或者至少比对其他争夺相同胃部生态位的微生物群的活性要低。虽然以前被认为是除幽门螺杆菌以外的不育菌，但最近基于广泛16S rDNA文库的证据表明，人类胃的微生物区系具有相当大的多样性。携带CAG PAI的幽门螺杆菌可能会诱导抗菌反应，对其中一些微生物有积极的作用，因此可能有助于幽门螺杆菌有效竞争。我们推测，幽门螺杆菌以CAG PAI依赖的方式诱导固有的抗菌宿主反应，改变了胃微生物群落，增加了幽门螺杆菌在胃利基的竞争优势。在这里，我们建议研究幽门螺杆菌对胃微生物群落的影响，进而研究该群落对幽门螺杆菌定植的影响。由于依赖CAG PAI的胃微生物区系，甚至肠道微生物区系的变化，可能在感染幽门螺杆菌后发生的不同结果中发挥重要作用，这项工作正好符合最近被纳入NIH路线图的人类微生物组倡议。公共卫生相关性：幽门螺杆菌是一种重要的胃部病原体，可在胃上皮细胞中诱导天然的抗菌素宿主反应。我们假设，这种抗菌反应改变了胃微生物群落，并增加了幽门螺杆菌在胃利基的竞争优势。

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.