Data from: The host response to the lung microbiome in Chromic Obstructive Pulmonary Disease

Rationale: The relatively sparse but diverse microbiome in human lungs may become less diverse in chronic obstructive pulmonary disease (COPD). This report examines the relationship of this microbiome to emphysematous tissue destruction, number of terminal bronchioles, infiltrating inflammatory cells, and host gene expression. Methods: A culture-independent pyrosequencing microbiome analysis was used to examine the V3-V5 regions of the bacterial 16S rDNA in 40 samples of lung from 5 patients with (GOLD 4) COPD and 28 samples from 4 donors (controls). A second protocol based on the V1-V3 regions was used to verify the bacterial microbiome results. Within lung tissue samples the microbiome was compared to results of microCT, infiltrating inflammatory cells measured using quantitative histology, and host gene expression. Results: A total of 10 Operational Taxonomic Units (OTUs) were found to be able to discriminate between control and GOLD 4 lung tissue, which included known pathogens such as Haemophilus influenzae. We also observed a decline in microbial diversity that was associated with emphysematous destruction, remodeling of the bronchiolar and alveolar tissue, and the infiltration of the tissue by CD4+ T cells. Specific OTUs were also associated with neutrophils, eosinophils and B cell infiltration (P<0.05). The expression profiles of 859 genes and 235 genes were associated with either enrichment or reductions of Firmicutes and Proteobacteria, respectively, at an FDR cutoff < 0.1. Conclusion: These results support the hypothesis that there is a host immune response to microorganisms within the lung microbiome that appears to contribute to the pathogenesis of COPD.

研究背景：人类肺部菌群虽相对稀疏但兼具多样性，而慢性阻塞性肺疾病（COPD）患者的肺部菌群多样性可能出现下降。本研究旨在探讨肺部菌群与肺气肿性组织破坏、终末细支气管数量、浸润性炎症细胞水平以及宿主基因表达之间的关联。
方法：本研究采用非培养焦磷酸测序菌群分析技术，对5例GOLD 4级COPD患者的40份肺组织样本，以及4名健康供体（对照组）的28份肺组织样本中的细菌16S rDNA的V3-V5可变区进行检测。同时采用基于V1-V3可变区的第二套实验方案，对细菌菌群的检测结果进行验证。针对肺组织样本，将菌群分析结果与微型计算机断层扫描（microCT）结果、定量组织学检测的浸润性炎症细胞水平以及宿主基因表达数据进行对比分析。
结果：本研究共鉴定出10个操作分类单元（Operational Taxonomic Units, OTUs），可用于区分对照组与GOLD 4级COPD患者的肺组织样本，其中包含已知致病菌流感嗜血杆菌（Haemophilus influenzae）。我们还观察到，菌群多样性的下降与肺气肿性组织破坏、细支气管及肺泡组织重塑以及CD4+ T细胞的组织浸润呈显著相关。特定OTUs还与中性粒细胞、嗜酸性粒细胞及B细胞浸润呈显著关联（P<0.05）。在错误发现率（False Discovery Rate, FDR）阈值<0.1的条件下，共有859个基因与厚壁菌门（Firmicutes）的丰度变化相关，235个基因与变形菌门（Proteobacteria）的丰度变化相关，二者均表现为丰度升高或降低。
结论：本研究结果支持下述假说：肺部菌群中的微生物可触发宿主免疫应答，该应答似乎参与了COPD的发病进程。