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

基本信息

批准号：
10375584
负责人：
Radhika Dhingra
金额：
$ 26.66万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10375584
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 Mediating Microbe Modeling Mucosal Immune Responses Mucositis Mucous Membrane Nasal Epithelium Nose Particulate Matter Pathway Analysis Placebo Control Population Predisposition Prevention Process Proteins Public Health Randomized Research Design Respiration Disorders Respiratory Disease 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

项目摘要

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.

抽象的全球暴露于木材颗粒，主要来自野火和生物质燃烧，是不断增长的来源颗粒物质，与许多呼吸系统疾病有关。成功防御伍德斯莫克需要熟练的免疫调节以维持整体稳态。建立对有效的免疫反应至关重要吸入抗原，已知鼻粘膜被大量真菌，细菌和病毒微型植入有机体。然而，呼吸道的疾病被认为是炎症的疾病，而不是感染的疾病。许多研究已经显示了共生驻留微生物及其代谢物在粘膜启动和/或进展中的作用炎。例如，包括哮喘和过敏性鼻炎在内的过敏和炎症性疾病的发生率是与缺乏微生物定植有关。鼻细胞因子在暴露于空气污染物（例如野火烟），并改变对病毒侮辱的反应的稳健性，例如流感和冠状病毒。因此，我们假设木烟暴露会诱导鼻微生物组的营养不良，并改变炎症性细胞因子特征，共同对呼吸健康产生影响。我们通过识别来解决这一差距并发的微生物群和细胞因子特征如何因接触伍德斯莫克的响应而变化。在这个跨界研究设计，我们将在多个时间点从健康个体中收集来自健康个体的鼻皮衬里样品。在受控的环境中暴露于伍德斯莫克或过滤空气，以产生微生物组和细胞因子概况。一旦在实验室处理样品后，我们将进行生物信息学和统计分析描述微生物组和细胞因子对伍德斯莫克的响应方式的急性改变。我们也会通过人口统计学和其他因素比较微生物组和细胞因子反应中的基线谱和反应。尽管我们在这里专注于伍兹莫克的暴露，这项工作具有多种应用，包括未来的特应性疾病研究，环境空气污染暴露，吸烟；以及呼吸道疾病疗法的潜在发展。