Woodsmoke-induced disruption of Nasal Microbiome and Cytokine Profiles

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ABSTRACT Global exposure to woodsmoke particles, primarily from wildfires and biomass burning, are an ever-increasing source of particulate matter, which is linked to many respiratory conditions. Successful defense against woodsmoke requires proficient immune regulation to maintain overall homeostasis. Critical to establishing an effective immune response to inhaled antigens, the nasal mucosa are known to be colonized by a large number of fungal, bacterial and viral micro- organisms. Disorders of the respiratory tract, however, are considered diseases of inflammation, not infection. Many studies have shown the role of commensal resident microbes and their metabolites in the initiation and/or progression of mucosal inflammation. For instance, incidence of allergic and inflammatory disease, including asthma and allergic rhinitis, is associated with a lack of diverse microbial colonization. Nasal cytokines are also known to be altered in those exposed to air pollutants (e.g., wildfire smoke), and to alter the robustness of response to viral insults, such as influenza and coronaviruses. Thus, we hypothesize that wood smoke exposure induces dysbiosis of the nasal microbiome and an altered inflammatory cytokine profile, which together have implications for respiratory health. We address this gap by identifying how concurrent microbiota and cytokine profiles change in response to exposure to woodsmoke. In this crossover study design, we will collect nasal epithelial lining fluid samples from healthy individuals at multiple time points post- exposure to either woodsmoke or filtered air in a controlled setting, in order to generate microbiome and the cytokine profiles. Once samples have been processed in the laboratory, we will conduct bioinformatic and statistical analyses to describe how acutely the microbiome and cytokines are concurrently altered in response to woodsmoke. We will also compare baseline profiles and responses in microbiome and cytokine responses by demographic and other factors. While we focus here on a woodsmoke exposure, this work has diverse applications including for future studies of atopic disease, ambient air pollution exposure, smoking; and potential development of therapies for respiratory disease.