The Lung Microbiome in Moderate and Severe Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder characterized by incompletely reversible airflow obstruction. Bacterial infection of the lower respiratory tract contributes to approximately 50% of COPD exacerbations. Even during periods of stable lung function, the lung harbors a community of bacteria, termed the microbiome. The role of the lung microbiome in the pathogenesis of COPD remains unknown. The COPD lung microbiome, like the healthy lung microbiome, appears to reflect microaspiration of oral microflora. Here we describe the COPD lung microbiome of 22 patients with Moderate or Severe COPD compared to 10 healthy control patients. The composition of the lung microbiomes was determined using 454 pyrosequencing of 16S rDNA found in bronchoalveolar lavage fluid. Sequences were analyzed using mothur, Ribosomal Database Project, Fast UniFrac, and Metastats. Our results showed a significant increase in microbial diversity with the development of COPD. The main phyla in all samples were Actinobacteria, Firmicutes, and Proteobacteria. Principal coordinate analyses demonstrated separation of control and COPD samples, but samples did not cluster based on disease severity. However, samples did cluster based on the use of inhaled corticosteroids and inhaled bronchodilators. Metastats analyses demonstrated an increased abundance of several oral bacteria in COPD samples.

慢性阻塞性肺疾病（Chronic obstructive pulmonary disease, COPD）是一类以不完全可逆性气流受限为特征的炎症性病症。下呼吸道细菌感染约占50%的COPD急性加重病例。即便处于肺功能稳定阶段，肺部仍定植有一类细菌群落，即微生物组（microbiome）。目前肺部微生物组在COPD发病机制中的作用仍未明确。与健康肺部微生物组相似，COPD患者的肺部微生物组似乎源自口腔菌群的微吸入。本研究对22例中重度COPD患者与10例健康对照者的肺部微生物组进行了分析：通过对支气管肺泡灌洗液中16S rDNA开展454焦磷酸测序（454 pyrosequencing），明确肺部微生物组的组成；测序序列采用mothur、核糖体数据库项目（Ribosomal Database Project）、Fast UniFrac以及Metastats进行分析。研究结果显示，随着COPD病情进展，微生物多样性显著提升。所有样本中的主要菌门为放线菌门（Actinobacteria）、厚壁菌门（Firmicutes）与变形菌门（Proteobacteria）。主坐标分析结果表明，对照组与COPD患者样本可实现有效区分，但样本并未按照疾病严重程度进行聚类。不过，样本可根据吸入性糖皮质激素（inhaled corticosteroids）与吸入性支气管扩张剂（inhaled bronchodilators）的使用情况完成聚类。Metastats分析显示，COPD样本中多种口腔细菌的丰度显著升高。