Understanding the Lung Microbiome in HIV-Infected and HIV-uninfected individuals

了解 HIV 感染者和 HIV 未感染者的肺部微生物组

• 批准号: 7937019
• 负责人: JAMES M BECK
• 金额: $ 76.15万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-23 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7937019
• 关键词: Animal Experimentation; Area; Clinical; Data; Data Collection; Development; Dyspnea; Environment; Epidemic; Experimental Designs; Funding; Gastrointestinal tract structure; Genitourinary system; HIV; Host Defense; Human; Human Microbiome; Immunologics; Incidence; Individual; Instruction; Investigation; Lead; Lower respiratory tract structure; Lung; Lung diseases; Measurement; Measures; Molecular; Nasal cavity; Nose; Oral cavity; Organ; Organism; Oropharyngeal; Pathogenesis; Pilot Projects; Pneumocystis; Pneumonia; Population; Principal Investigator; Production; Prophylactic treatment; Pulmonary Emphysema; Reporting; Research Personnel; Research Subjects; Respiratory System; Respiratory Tract Infections; Respiratory tract structure; Sampling; Site; Skin; Smoker; Smoking; Sputum; Stomach; Symptoms; Techniques; Testing; Time; Translational Research; Work; base; body system; cigarette smoking; clinically relevant; gastrointestinal system; in vivo; insight; microbial; microbiome; mouse model; non-smoking; pathogen; pulmonary function; respiratory

DESCRIPTION (provided by applicant): The Human Microbiome Project originally focused on the microbiome of the nasal and oral cavities, the skin, the gastrointestinal tract, and the urogenital tract. Like these other organs and organ systems, the respiratory tract is continually exposed to the external environment, but virtually nothing is known about the microbiome of the lung. Indeed, the presence of a lung microbiome in normal individuals has yet to be established conclusively. Since the beginning of the HIV epidemic in the 1980's, HIV-infected individuals have been known to be extremely susceptible to pneumonias caused by opportunistic and non-opportunistic organisms. Comparison of the microbiome of HIV-infected and HIV-uninfected individuals, then, should be a productive way to begin to explore changes in the lung microbiome. Because the microbiome may shift subtly (or not so subtly) over time, we have constructed an experimental design in which each research subject can also serve as his/her own control. In specific aim 1, we will employ molecular and advanced culture-based techniques for the characterization of the bacterial microbiota of the lower respiratory tract in HIV-infected and HIV-uninfected individuals longitudinally. We will compare these data with those obtained from the nasal cavity, the oropharynx, and the stomach. We hypothesize that significant differences will be present, even after controlling for clinical factors. In specific aim 2, we will compare data from currently smoking and non-smoking individuals (never- or former-smokers), and correlate these data with measurements of pulmonary function longitudinally. These studies will assist with our understanding of the pathogenesis of early emphysema development in HIV-infected individuals. We hypothesize that the rate of decline in both smoking and non-smoking HIV-infected subjects will exceed the rate measured in smoking and non-smoking HIV-uninfected subjects, and that this rate of decline will correlate with microbial diversity. Furthermore, we anticipate that microbiota data will relate directly to subject reports of sputum production and dyspnea. In specific aim 3, we will compare colonization with Pneumocystis in HIV-infected and HIV- uninfected individuals. This is our proposal for a collaborative pilot study that will involve all funded centers, but will develop in greater detail by the Steering Committee. We will partner with the other funded data collection sites to determine whether Pneumocystis colonization alters the microbiome. RELEVANCE (See instructions): Virtually nothing is known about the microbiome of the normal lung, and so beginning characterization of the microflora of the lung is an area of considerable scientific and clinical relevance. These studies will characterize the microbiome of the lung and will provide insights into the development of lung disease in HIV-infected and HIV-uninfected populations.

描述（由申请人提供）：人类微生物组项目最初专注于鼻腔和口腔、皮肤、胃肠道和泌尿生殖道的微生物组。像这些其他器官和器官系统一样，呼吸道持续暴露于外部环境，但对肺部的微生物组几乎一无所知。事实上，正常个体中肺部微生物组的存在尚未最终确定。自20世纪80年代HIV流行开始以来，已知HIV感染者极易感染由机会性和非机会性生物体引起的肺炎。因此，比较HIV感染者和未感染者的微生物组应该是开始探索肺部微生物组变化的一种有效方法。由于微生物组可能会随着时间的推移而微妙地（或不那么微妙地）发生变化，我们构建了一个实验设计，其中每个研究对象也可以作为他/她自己的对照。在具体目标1中，我们将采用分子和先进的基于培养的技术来纵向表征HIV感染和HIV未感染个体下呼吸道的细菌微生物群。我们将这些数据与从鼻腔、口咽和胃获得的数据进行比较。我们假设，即使在控制了临床因素后，也会存在显著差异。在具体目标2中，我们将比较目前吸烟者和非吸烟者（从不吸烟者或以前吸烟者）的数据，并将这些数据与肺功能的纵向测量结果相关联。这些研究将有助于我们了解HIV感染者早期肺气肿发展的发病机制。我们假设吸烟和不吸烟的HIV感染者的下降率将超过吸烟和不吸烟的HIV未感染者的下降率，并且这种下降率将与微生物多样性相关。此外，我们预计微生物群数据将与受试者的痰液产生和呼吸困难报告直接相关。在具体目标3中，我们将比较肺孢子虫在HIV感染和未感染HIV的个体中的定殖。这是我们关于合作试点研究的建议，将涉及所有受资助的中心，但将由指导委员会制定更详细的内容。我们将与其他受资助的数据收集网站合作，以确定肺孢子虫定植是否改变了微生物组。相关性（参见说明）：事实上，对正常肺的微生物组一无所知，因此开始表征肺的微生物菌群是一个具有相当大的科学和临床相关性的领域。这些研究将表征肺部的微生物组，并将为艾滋病毒感染和未感染艾滋病毒的人群中肺部疾病的发展提供见解。