Human Sputum Microbiome Composition and Sputum Inflammatory Cell Profiles Are Altered with Controlled Wood Smoke Exposure as a Model for Wildfire Smoke

<b>Rationale:</b> Wood smoke exposure is increasing worldwide because of the increase in wildfire events. Various studies have associated exposure to wildfire-derived smoke with adverse respiratory conditions. However, the mechanism by which this occurs is unknown. Previous studies using wood smoke as a model of wildfire smoke have focused on the respiratory immune response and have reported increased neutrophil percentage and cytokine production in airway samples. The effect of wood smoke on the respiratory microbiome, however, has not been examined. <b>Objectives:</b> The objective of this study was to evaluate whether inhaled wood smoke exposure can alter the respiratory microbiome in humans. <b>Methods:</b> Healthy volunteers (<i>N</i> = 54) were subjected to controlled wood smoke exposure (500 μg/m³) for 2 hours, and induced sputum samples were collected and processed for microbiome analysis, immune mediators, and cell differentials at baseline and at 6 hours and 24 hours after exposure. A negative binomial mixed model analysis examined associations between microbiome components and inflammatory cells in sputum. <b>Measurements and Main Results:</b> After wood smoke exposure, although sputum microbiome diversity remained unchanged, the microbiome composition was altered, particularly the abundance of several low-abundance bacteria, including <i>Fretibacterium</i> and <i>Selenomonas</i>, indicating that this inhalational exposure can alter the composition of the sputum microbiome. In addition, a significant decrease in macrophage cells was observed at 24 hours without a significant change in neutrophils. We further found small but significant associations between different taxa and macrophages (per milligram of sputum), including a negative association with <i>Fretibacterium</i>. <b>Conclusions:</b> Together, these findings demonstrate that inhalational wood smoke exposure can modify several low-abundance bacteria within the respiratory microbiome and that these changes are associated with sputum inflammatory cell alterations, providing insights for future studies to focus on respiratory innate immune host-microbiome crosstalk in the context of environmental exposures.