Helicobacter pylori and the gastric microbial community in rhesus macaques

恒河猴的幽门螺杆菌和胃微生物群落

• 批准号: 7843477
• 负责人: JAY V. SOLNICK
• 金额: $ 19.13万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-15 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7843477
• 关键词: Antibiotics; Cellular biology; Communities; Cytotoxin; Development; Epithelium; Gastric Tissue; Gastric mucosa; Gastritis; Genes; Helicobacter pylori; Histopathology; Human; Human Microbiome; Immune; Immune response; In Vitro; Individual; Infection; Inflammation; Inflammatory Response; Knock-out; Libraries; Macaca; Macaca mulatta; Measures; Modeling; Organism; Outcome; PI3 gene; Pathogenicity Island; Peptic Ulcer; Proteins; Recombinant DNA; Sequence Analysis; Sterility; Stomach; Testing; United States National Institutes of Health; Up-Regulation; Work; antimicrobial; evidence base; gut microbiota; in vivo; malignant stomach neoplasm; microbial community; pathogen; public health relevance; response; tool

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：幽门螺杆菌通常感染胃部，在那里它会引起所有人的炎症（胃炎），并在某些人中引起消化性溃疡疾病或胃癌。与胃癌和消化性溃疡相关的细菌因子研究得最好的是cag致病性岛（cag PAI）。我们最近使用恒河猴模型证明幽门螺杆菌以cag - pai依赖的方式诱导抗微生物宿主反应，其中包括胃粘膜中2-防御素2、elafin、siderocalin和其他先天免疫效应分子的上调。乍一看，似乎矛盾的是，幽门螺杆菌水平获得PAI服务，至少部分，诱导抗菌先天免疫反应。一种可能性是，这些抗菌蛋白可能对幽门螺杆菌没有活性，或者至少不如对竞争同一胃生态位的其他微生物群有活性。虽然以前认为除了幽门螺杆菌外是无菌的，但最近基于广泛的16S rDNA文库的证据表明，人类胃的微生物群具有相当大的多样性。携带cag PAI的幽门螺杆菌可能会诱导对这些微生物的抗菌反应，因此可能有助于幽门螺杆菌有效地竞争。我们假设幽门螺杆菌以cag PAI依赖的方式诱导先天抗菌宿主反应，这改变了胃微生物群落，增加了幽门螺杆菌在胃生态位中的竞争优势。在此，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。由于胃微生物群，甚至肠道微生物群的cag pai依赖性变化可能对幽门螺杆菌感染后发生的各种结果很重要，因此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，可诱导胃上皮内的先天抗微生物宿主反应。我们假设这种抗菌反应改变了胃微生物群落，增加了幽门螺杆菌在胃生态位中的竞争优势。