Lung microbiome dynamics in COPD exacerbations

Lung microbiome dynamics in COPD exacerbations
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DOI:
10.1183/13993003.01406-2015
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发表时间:
2016-04-01
影响因子:
24.3
通讯作者:
Brown, James R.
Brown, James R.
中科院分区:
医学1区
文献类型:
--
作者:
Wang, Zhang;Bafadhel, Mona;Brown, James R.

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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) 严重程度中发挥着重要作用。然而,COPD 恶化期间肺微生物组的动态及其在疾病病因学中的潜在作用仍然知之甚少。我们对 87 名 COPD 受试者收集的 476 份痰样本进行了肺微生物组的纵向 16S 核糖体 RNA 调查,四次就诊定义为稳定状态、恶化、治疗后 2 周和恢复 6 周。我们的分析揭示了动态的肺 微生物群的变化似乎与恶化事件相关并指示特定的恶化表型。抗生素和类固醇治疗似乎对肺部微生物群有不同的影响。我们描述了肺微生物组的微生物相互作用网络,并表明一些细菌操作分类单位(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,几种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 患者的肺微生物组动态,并强调了其作为生物标志物的潜力,并可能成为未来呼吸治疗的目标。
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.