Computational Biology, Target Sciences, GSK R&D, Collegeville, PA, USA These authors contributed equally.
Respiratory Medicine Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK These authors contributed equally.
Eur Respir J. 2016 Apr;47(4):1082-92. doi: 10.1183/13993003.01406-2015. Epub 2016 Feb 25.
Increasing evidence suggests that the lung microbiome plays an important role in chronic obstructive pulmonary disease (COPD) severity. However, the dynamics of the lung microbiome during COPD exacerbations and its potential role in disease aetiology remain poorly understood.We completed a longitudinal 16S ribosomal RNA survey of the lung microbiome on 476 sputum samples collected from 87 subjects with COPD at four visits defined as stable state, exacerbation, 2 weeks post-therapy and 6 weeks recovery.Our analysis revealed a dynamic lung microbiota where changes appeared to be associated with exacerbation events and indicative of specific exacerbation phenotypes. Antibiotic and steroid treatments appear to have differential effects on the lung microbiome. We depict a microbial interaction network for the lung microbiome and suggest that perturbation of a few bacterial operational taxonomic units, in particular Haemophilus spp., could greatly impact the overall microbial community structure. Furthermore, several serum and sputum biomarkers, in particular sputum interleukin-8, appear to be highly correlated with the structure and diversity of the microbiome.Our study furthers the understanding of lung microbiome dynamics in COPD patients and highlights its potential as a biomarker, and possibly a target, for future respiratory therapeutics.
越来越多的证据表明,肺部微生物组在慢性阻塞性肺疾病(COPD)的严重程度中起着重要作用。然而,COPD 恶化期间肺部微生物组的动态变化及其在疾病发病机制中的潜在作用仍知之甚少。我们对 87 名 COPD 患者的 476 份痰样本进行了为期 16S 核糖体 RNA 的纵向肺部微生物组调查,这些样本在四次就诊时采集,分别定义为稳定状态、恶化、治疗后 2 周和恢复后 6 周。我们的分析揭示了一个动态的肺部微生物群,其中变化似乎与恶化事件有关,并提示了特定的恶化表型。抗生素和类固醇治疗似乎对肺部微生物组有不同的影响。我们描绘了肺部微生物组的微生物相互作用网络,并提出少数细菌操作分类单元(特别是嗜血杆菌属)的扰动可能会极大地影响整体微生物群落结构。此外,一些血清和痰生物标志物,特别是痰白细胞介素-8,似乎与微生物组的结构和多样性高度相关。我们的研究进一步了解了 COPD 患者肺部微生物组的动态变化,并强调了其作为未来呼吸治疗的生物标志物和潜在靶点的潜力。