The lung microbiota in cystic fibrosis

描述(由申请人提供)：本申请涉及广泛的挑战领域(15)翻译科学和特定挑战主题，15-HL-104：表征呼吸道和/或肠道微生物区系对肺部疾病的存在和临床表型的作用和影响。进行性肺部疾病是囊性纤维化患者疾病和死亡的主要原因，它受到呼吸道免疫防御机制的强烈影响，而个体免疫反应的主要贡献者是在呼吸道中定居的微生物。目前，人们对CF患者呼吸道微生物区系或肺部疾病与呼吸道微生物群落变化的关系知之甚少。国家心肺血液研究所的一项任务是更好地了解个体微生物群与肺部疾病之间的关系。这一认识不仅将对肺部疾病的病因和机制提供重要的见解，而且将为快速将研究成果转化为预防和治疗慢性肺病的改进方法提供巨大的潜力。该项目的长期目标是了解囊性纤维症患者肺部微生物区系与肺部疾病进展之间的关系。我们将分析过去十年中从数百名CF患者中获得的大量现有的痰样本。我们将在CF肺分析中利用微生物群落的培养独立分析来表征这些人的肺微生物区系，并将呼吸道微生物群落的变化与患者临床状态的变化联系起来。在相对健康和疾病期间，以及临床状态相似或不同的患者之间，将进行个体内微生物群落结构的比较，以将肺微生物区系的特定生态和功能特征与CF肺部疾病的进展联系起来。 公共卫生相关性：慢性呼吸道感染引起的进行性肺部疾病是囊性纤维症患者患病和死亡的主要原因。最近的研究表明，在肺微生物区系中，参与肺部感染的微生物种类比以前认为的要多得多，也更复杂。然而，目前关于肺微生物区系的结构(即，存在的物种的确切类型和每种微生物的相对丰度)或这种结构的变化如何影响CF肺部疾病的进展，目前知之甚少。该项目的长期目标是了解肺微生物区系与CF患者肺部疾病进展之间的关系。

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (15) Translational Science and specific Challenge Topic, 15-HL-104: Characterize the role and effects of the respiratory and/or intestinal microbiota on the presence and clinical phenotype of lung disease. The progressive lung disease that is the primary cause of illness and death in persons with cystic fibrosis (CF) is strongly influenced by immunological defense mechanisms in the airways, and a major contributor to an individual's immune response is the microorganisms that have established themselves in the airways. Currently, very little is known about the microbiota of the respiratory tract in persons with CF or the relationship of lung disease to changes in the microbial community of the airways. A mission of the National Heart, Lung and Blood Institute is to better understand the relationships between individual microbiomes and lung disease. This understanding will not only provide important insights into the causes and mechanisms of lung disease, but also offer great potential for rapid translation of research results into improved approaches for prevention and treatment of CF lung disease. The long-term objective of this project is to understand the relationship between the lung microbiota and the progression of lung disease in persons with cystic fibrosis (CF). We will analyze a large existing repository of sputum samples obtained from several hundred CF patients during the past decade. We will utilize culture-independent analysis of the microbial community in the CF lung analyses to characterize the lung microbiota of these individuals and correlate changes in airway microbial community to changes in patient clinical status. Comparison of microbial community structure within individual patients during periods of relative health and illness, and between patients with similar or different clinical status will be done to associate specific ecologic and functional characteristics of the lung microbiota with the progression of CF lung disease. PUBLIC HEALTH RELEVANCE: Progressive lung disease, resulting from chronic infection of the airways, is the primary cause of illness and death in persons with cystic fibrosis (CF). Recent studies indicate that the number of microbial species involved in lung infection in CF (the CF lung microbiota) is much larger and more complex than previously believed. Nevertheless, currently little is known about how the structure of the lung microbiota (i.e., the precise types of species present and the relative abundance of each) or changes in this structure influence the progression of lung disease in CF. The long-term objective of this project is to understand the relationship between the lung microbiota and the progression of lung disease in persons with CF.