Woodsmoke-induced disruption of Nasal Microbiome and Cytokine Profiles

木烟引起的鼻微生物组和细胞因子谱的破坏

• 批准号: 10196055
• 负责人: Radhika Dhingra
• 金额: $ 15.55万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10196055
• 关键词: Acute; Address; Air Pollutants; Air Pollution; Allergic; Allergic rhinitis; Antigens; Asthma; Bioinformatics; Biological Response Modifiers; Biomass; Buffers; Cause of Death; Cells; Cigarette; Coronavirus; Cross-Over Studies; Data; Disease; Dose; Ecosystem; Electronic cigarette; Enzyme-Linked Immunosorbent Assay; Epidemiology; Epithelial Cells; Exposure to; Feedback; Foundations; Future; Homeostasis; Host Defense; Hour; Immune; Immune response; Immune system; Immunologics; Incidence; Individual; Inflammation; Inflammatory; Influenza; Inhalation; Inhalation Exposure; Intestinal Mucosa; Knowledge; Laboratories; Lead; Link; Liquid substance; Lung diseases; Mediating; Microbe; Modeling; Mucosal Immune Responses; Mucositis; Mucous Membrane; Nasal Epithelium; Nose; Particulate Matter; Pathway Analysis; Placebos; Population; Predisposition; Prevention; Process; Proteins; Public Health; Randomized; Research Design; Respiration Disorders; Respiratory Mucosa; Respiratory System; Respiratory Tract Infections; Role; Sampling; Signal Transduction; Smoke; Smoking; Source; Sputum; Statistical Data Interpretation; Structure of mucous membrane of nose; System; Time; Tissues; Viral; Wildfire; Work; air filter; ambient air pollution; asthmatic; beta diversity; chemokine; cigarette smoke; commensal bacteria; cytokine; dysbiosis; exposed human population; gut microbiome; host microbiota; human subject; immunoregulation; influenzavirus; microbial; microbial colonization; microbiome; microbiota; microorganism; nasal microbiome; novel; particle; particle exposure; pathogen; pollutant; public health relevance; resident commensals; respiratory; respiratory disease/disorder therapy; respiratory health; respiratory microbiome; respiratory pathogen; response; sex; therapy development; wood smoke

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.

摘要 全球暴露于林烟颗粒，主要是来自野火和生物质燃烧，是一个不断增加的来源 颗粒物，这与许多呼吸系统疾病有关。成功防御林烟需要 精通免疫调节，维持整体动态平衡。对建立有效的免疫反应至关重要 吸入抗原后，鼻黏膜已知被大量真菌、细菌和病毒微 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 已显示共生微生物及其代谢物在粘膜的启动和/或进展中的作用 发炎。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为 与缺乏多样化的微生物定植有关。鼻腔细胞因子也已知会在暴露于空气中的人中改变。 空气污染物(例如，野火烟雾)，并改变对病毒侮辱的反应的健壮性，如流感和 冠状病毒。因此，我们假设接触木材烟雾会导致鼻部微生物群落的失调和改变。 炎性细胞因子分布，这些因素共同影响呼吸健康。我们通过确定以下内容来解决这一差距 同时存在的微生物区系和细胞因子谱如何随着暴露在林烟中而发生变化。在这个跨界车中 研究设计，我们将在术后多个时间点收集健康人的鼻黏膜上皮液样本。 暴露在受控环境中的木烟或过滤空气中，以产生微生物群和细胞因子 配置文件。一旦样本在实验室中处理完毕，我们将进行生物信息学和统计分析，以 描述微生物组和细胞因子同时对林烟的反应有多剧烈。我们还将 按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情况和反应。而当 我们在这里关注的是烟雾暴露，这项工作有多种应用，包括未来对特应性疾病的研究， 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。