Background: The human microbiome has a role in the development of human diseases. Individual microbiome profiles are highly personalized, though many species are shared. Understanding the relationship between the human microbiome and disease may inform future individualized treatments. Specifically, the blood microbiome, once believed sterile, may be a surrogate for some lung and gut microbial characteristics. We sought associations between the blood microbiome and lung-relevant host factors. Methods: Based on reads not mapped to the human genome, we detected microbial nucleic acid signatures in peripheral blood RNA-sequencing for 2,590 current and former smokers with and without chronic obstructive pulmonary disease (COPD) from the COPDGene study. We used the GATK microbial pipeline PathSeq to infer microbial profiles. We tested associations between the inferred profiles and lung disease relevant phenotypes and examined links to host gene expression pathways. Results: The four phyla with highest abundance across all subjects were Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. We observed associations between exacerbation phenotypes and the relative abundance of Staphylococcus, Acidovorax and Cupriavidus. The genus Flavobacterium was associated with emphysema and change in emphysema. Our host-microbiome interaction analysis revealed clustering of genera associated with emphysema, systemic inflammation, airway remodeling and exacerbations, through links to lung-relevant host pathways. Conclusions: This study is the first to identify a bacterial microbiome signature in the peripheral blood of current and former smokers. Understanding the relationships between the systemic microbial populations and lung disease severity may inform novel interventions and aid in the understanding of exacerbation phenotypes.

中文翻译：

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COPD患者外周血微生物特征

背景：人类微生物组在人类疾病的发展中具有重要作用。尽管许多物种是共享的，但各个微生物组的配置文件还是高度个性化的。了解人类微生物组与疾病之间的关系可能会为将来的个体化治疗提供依据。具体来说，曾经被认为是无菌的血液微生物组可能是某些肺和肠道微生物特征的替代物。我们寻求血液微生物组和肺相关宿主因素之间的关联。方法：根据未映射到人类基因组的读数，我们从COPDGene研究中检测了2,590名有和没有慢性阻塞性肺疾病（COPD）的当前和以前吸烟者外周血RNA测序中的微生物核酸特征。我们使用GATK微生物管道PathSeq推断微生物概况。我们测试了推断的概况和肺部疾病相关表型之间的关联，并检查了与宿主基因表达途径的联系。结果：所有受试者中四个丰度最高的门是Proteobacteria，Actinobacteria，Firmicutes和Bacteroidetes。我们观察到加重表型和葡萄球菌，嗜酸菌和铜绿菌的相对丰度之间的关联。黄杆菌属与肺气肿和肺气肿的改变有关。我们的宿主-微生物组相互作用分析揭示了与肺气肿，全身性炎症，气道重塑和恶化相关的属簇，通过与肺相关的宿主途径相关联。结论：这项研究是第一个鉴定当前和以前吸烟者外周血中细菌微生物组特征的方法。