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

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。像其他器官和器官系统一样，呼吸道也不断地暴露在外部环境中，但人们对肺部的微生物群几乎一无所知。事实上，在正常个体中是否存在肺微生物还有待最终确定。自1980年代艾滋病毒开始流行以来，人们知道感染艾滋病毒的人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）变化，我们已经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感染者和未感染hiv的个体的下呼吸道细菌微生物群。我们将把这些数据与从鼻腔、口咽和胃中获得的数据进行比较。我们假设，即使在控制了临床因素后，仍会存在显著差异。在具体目标2中，我们将比较当前吸烟和非吸烟个体（从不吸烟或曾经吸烟）的数据，并将这些数据与肺功能的测量结果纵向关联。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感染者的下降速度将超过吸烟和不吸烟的hiv感染者的下降速度，并且这种下降速度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报告的痰产生和呼吸困难直接相关。在具体目标3中，我们将比较肺囊虫在HIV感染和HIV未感染个体中的定植。这是我们的合作试点研究的建议，将涉及所有资助的中心，但将由指导委员会制定更详细的内容。我们将与其他资助的数据收集站点合作，以确定肺囊虫定植是否会改变微生物组。相关性（见说明书）：实际上我们对正常肺的微生物群一无所知，因此开始描述肺微生物群是一个具有相当大的科学和临床相关性的领域。这些研究将描述肺部微生物组的特征，并将为艾滋病毒感染和未感染人群肺部疾病的发展提供见解。

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.