RT Journal Article
SR Electronic
T1 Peripheral blood microbial signatures in COPD
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.31.126367
DO 10.1101/2020.05.31.126367
A1 Jarrett D. Morrow
A1 Peter J. Castaldi
A1 Robert P. Chase
A1 Jeong H. Yun
A1 Sool Lee
A1 Yang-Yu Liu
A1 Craig P. Hersh
A1 the COPDGene Investigators
YR 2020
UL http://biorxiv.org/content/early/2020/06/01/2020.05.31.126367.abstract
AB 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.Competing Interest StatementDrs. Morrow, Chase, Yun, Lee and Liu declare that they have no competing interests related to this manuscript. Dr. Castaldi has received consulting fees and grant support from GSK. Dr. Hersh has received consulting fees from AstraZeneca, Concert Pharmaceuticals, Mylan, and 23andMe and grant support from Boehrinher Ingelheim and Novartis.