Peripheral blood microbial signatures in COPD

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.