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）转化科学和特定的挑战主题15-HL-104：表征呼吸道和/或肠道微生物群对肺部疾病的存在和临床表型的作用和影响。作为囊性纤维化（CF）患者疾病和死亡的主要原因的进行性肺病受到气道中免疫防御机制的强烈影响，并且个体免疫应答的主要贡献者是已经在气道中建立的微生物。目前，对CF患者呼吸道的微生物群或肺部疾病与气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使命是更好地了解个体微生物组与肺部疾病之间的关系。这种理解不仅将为肺部疾病的原因和机制提供重要的见解，而且还为将研究结果快速转化为预防和治疗CF肺部疾病的改进方法提供了巨大的潜力。该项目的长期目标是了解囊性纤维化（CF）患者肺部微生物群与肺部疾病进展之间的关系。我们将分析在过去十年中从数百名CF患者中获得的大量现有痰液样本库。我们将利用CF肺分析中微生物群落的非培养分析来表征这些个体的肺微生物群，并将气道微生物群落的变化与患者临床状态的变化相关联。将比较相对健康和疾病期间个体患者内以及具有相似或不同临床状态的患者之间的微生物群落结构，以将肺微生物群的特定生态和功能特征与CF肺病的进展相关联。 公共卫生相关性：由气道慢性感染引起的进行性肺病是囊性纤维化（CF）患者患病和死亡的主要原因。最近的研究表明，CF中涉及肺部感染的微生物物种（CF肺微生物群）的数量比以前认为的要大得多，也更复杂。然而，目前对肺微生物群的结构（即，存在的物种的精确类型和每种物种的相对丰度）或该结构的变化影响CF中肺病的进展。该项目的长期目标是了解CF患者肺部微生物群与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.