Peripheral blood microbial signatures in current and former smokers

Abstract

The human microbiome has a role in the development of multiple 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. We hypothesize the blood microbiome signature may be a surrogate for some lung microbial characteristics. We sought associations between the blood microbiome signature and lung-relevant host factors. Based on reads not mapped to the human genome, we detected microbial nucleic acids through secondary use of peripheral blood RNA-sequencing from 2,590 current and former smokers with and without chronic obstructive pulmonary disease (COPD) from the COPDGene study. We used the Genome Analysis Toolkit (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. We replicated our analyses using a second independent set of blood RNA-seq data from 1,065 COPDGene study subjects and performed a meta-analysis across the two studies. The four phyla with highest abundance across all subjects were Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. In our meta-analysis, we observed associations (q-value < 0.05) between Acinetobacter, Serratia, Streptococcus and Bacillus inferred abundances and Modified Medical Research Council (mMRC) dyspnea score. Current smoking status was associated (q < 0.05) with Acinetobacter, Serratia and Cutibacterium abundance. All 12 taxa investigated were associated with at least one white blood cell distribution variable. Abundance for nine of the 12 taxa was associated with sex, and seven of the 12 taxa were associated with race. Host-microbiome interaction analysis revealed clustering of genera associated with mMRC dyspnea score and smoking status, through shared links to several host pathways. This study is the first to identify a bacterial microbiome signature in the peripheral blood of current and former smokers. Understanding the relationships between systemic microbial signatures and lung-related phenotypes may inform novel interventions and aid understanding of the systemic effects of smoking.

Hepatitis C and HIV detection by blood RNA-sequencing in cohort of smokers

“…We created interferon scores using the RNA-seq gene expression data to observe correlation between detection of infections and host response (see “Methods”) 6 . We integrated the viral detection data with the scores for the interferon alpha and interferon gamma pathways to observe score values in the subjects with HCV detection compared with the subjects lacking viral detection.…”

“…Subjects were at least one month removed from an acute respiratory infection. The RNA-sequencing and data processing methods were reported previously 6 , 19 . Briefly, paired end reads with nominal 75 bp length were generated on an Illumina HiSeq 2500 flow cell.…”

“…Using reads that were not mapped to the human genome during the gene expression analysis, we detected viral signatures in the COPDGene 5-year follow-up whole blood RNA-seq data using PathSeq, the microbial detection pipeline from the Genome Analysis Toolkit (GATK4) 23 , as described in a previous microbiome study 6 . Filtering of the unmapped reads was performed using PathSeq and the host reference in the GATK Resource Bundle 23 .…”

Smoking-induced microbial dysbiosis in health and disease

“…Antibiotics administration to mice lacking the airways secretory immunoglobulin A (IgA) inhibited the emphysema-like symptoms in these mice and reduced lung remodeling and inflammation, suggesting that the microbiome in COPD may have deleterious effects on disease progression [ 83 ]. Microbiome signals from other anatomical sites like the gut may also affect COPD progression [ 84 , 85 ].…”

Microbiome First Approaches to Rescue Public Health and Reduce Human Suffering

“…The tobacco smoking-nicotine-cycle has been shown to be intimately connected to microbiome status [144]. For example, a recent study established that there is specific microbiome-based signature in human blood that identifies and distinguishes former and current smokers [145]. Other research groups found that former and current cigarette smokers could be distinguished from never smokers based on fecal microbiota [146].…”