Smoking is associated with quantifiable differences in the human lung DNA virome and metabolome

Background: The role of commensal viruses in humans is poorly understood, and the impact of the virome on lung health and smoking-related disease is particularly understudied. Methods: Genetic material from acellular bronchoalveolar lavage fluid was sequenced to identify and quantify viral members of the lower respiratory tract which were compared against concurrent bronchoalveolar lavage bacterial, metabolite, cytokine and cellular profiles, and clinical data. Twenty smoker and 10 nonsmoker participants with no significant comorbidities were studied. Results: Viruses that infect bacteria (phages) represented the vast majority of viruses in the lung. Though bacterial communities were statistically indistinguishable across smokers and nonsmokers as observed in previous studies, lung viromes and metabolic profiles were significantly different between groups. Statistical analyses revealed that changes in viral communities correlate most with changes in levels of arachidonic acid and IL-8, both potentially relevant for chronic obstructive pulmonary disease (COPD) pathogenesis based on prior studies. Conclusions: Our assessment of human lung DNA viral communities reveals that commensal viruses are present in the lower respiratory tract and differ between smokers and nonsmokers. The associations between viral populations and local immune and metabolic tone suggest a significant role for virome-host interaction in smoking related lung disease.