Woodsmoke-induced disruption of Nasal Microbiome and Cytokine Profiles

摘要 全球暴露于主要来自野火和生物质燃烧的木材烟雾颗粒，是一个不断增加的污染源。 颗粒物，这与许多呼吸系统疾病有关。成功防御木烟需要 熟练的免疫调节，以维持整体稳态。建立有效的免疫反应至关重要， 吸入的抗原，鼻粘膜已知被大量的真菌、细菌和病毒微生物定殖， 有机体然而，呼吸道疾病被认为是炎症疾病，而不是感染。许多研究 已经显示了肠道驻留微生物及其代谢物在粘膜炎的发生和/或进展中的作用， 炎症例如，包括哮喘和过敏性鼻炎在内的过敏性和炎症性疾病的发病率是 与缺乏多样的微生物定植有关。鼻细胞因子也已知在暴露于 空气污染物（例如，野火烟雾），并改变对病毒损伤（如流感和 冠状病毒因此，我们假设，木材烟雾暴露诱导鼻微生物组的生态失调， 炎性细胞因子谱，它们一起对呼吸健康有影响。我们通过识别 同时存在的微生物群和细胞因子谱如何响应于暴露于木材烟雾而改变。在这个交叉 研究设计，我们将在术后多个时间点收集健康个体的鼻上皮衬里液样品， 在受控环境中暴露于木材烟雾或过滤空气，以产生微生物组和细胞因子 数据区.一旦样本在实验室处理，我们将进行生物信息学和统计分析， 描述了微生物组和细胞因子如何在响应木材烟雾时同时发生急剧变化。我们还将 根据人口统计学和其他因素比较微生物组和细胞因子反应的基线特征和反应。而 我们在这里集中在木材烟雾暴露，这项工作有不同的应用，包括未来的特应性疾病的研究， 环境空气污染暴露、吸烟;以及呼吸系统疾病治疗的潜在发展。

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.