Characterizing the Respiratory Microbiome Via a Novel, Non-Invasive Technique

通过新颖的非侵入性技术表征呼吸道微生物组

• 批准号: 9034939
• 负责人: Sara Adar
• 金额: $ 23.25万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-02-18 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9034939
• 关键词: Adult; Air; Air Pollution; Bacteria; Bioinformatics; Biological; Biological Markers; Breathing; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Cells; Chronic; Chronic Obstructive Asthma; Clinical; Clinical Research; Communicable Diseases; Communities; Development; Diagnostic; Disease; Effectiveness; Environment; Environmental Pollutants; Epidemiologic Studies; Epidemiology; Exhalation; Future; Gastrointestinal tract structure; General Population; Health; Hospitals; Household; Human; Human body; Individual; Indoor Air Pollution; Infection; Inflammatory; Inflammatory Response; Lead; Life; Link; Lung; Lung diseases; Measurement; Measures; Mediating; Methods; Michigan; Microbe; Microbiology; Nasal Lavage Fluid; Nose; Oral; Oral cavity; Oropharyngeal; Participant; Particulate Matter; Patients; Persons; Pilot Projects; Play; Predisposition; Procedures; Process; Public Health; Research; Research Personnel; Respiratory physiology; Risk; Role; Sampling; Schedule; Sedation procedure; Severity of illness; Skin; Sterility; Structure; Swab; Techniques; Testing; Toxic Environmental Substances; Universities; Vagina; Work; air sampling; ambient air pollution; cost; cytokine; epidemiology study; high risk; improved; microbial; microbial community; microbiome; novel; novel marker; population based; programs; public health relevance; pulmonary function; research study; respiratory; survival prediction

 DESCRIPTION (provided by applicant): Bacteria are prevalent throughout the human body, residing at all interfaces with the external environment. These microbes, which outnumber human cells ten to one, are highly physiologically active and known to influence the health of their host. Although most studies to date have focused on microbes of the skin, oropharynx, gastrointestinal tract, and vagina, there is now an understanding that the lungs are not sterile, as was once believed. In fact, evidence shows that microbial burden and diversity in the lungs differs between healthy individuals and those with lung disease. Additionally, microbial composition in the lungs has been linked to respiratory disease severity. Since it is known that microbial communities in the gut can metabolize environmental toxicants, stimulate host inflammatory response, and increase risk of host infection, it is likely that respiratory microbes also play an important role in human health. A major challenge to researching the respiratory microbiome is the lack of a well-established, non-invasive measure in the lungs. Bronchoalveolar lavage is the most direct approach to measure the lungs, but it is an invasive procedure performed under sedation at the hospital. This makes it too burdensome on participants and cost-prohibitive for large clinical and epidemiology studies. To overcome these limitations, the aim of this exploratory study is to systematically investigate exhaled breath condensate as a novel, non-invasive medium to characterize the respiratory microbiome. Because exhaled breath condensate may reflect several inter-connected biological compartments, we plan to characterize the microbial communities of concurrent samples of exhaled breath condensate, bronchoalveolar lavage fluid, oral wash, nasal swab, fecal, and inspired air samples collected from 18 healthy individuals. Specifically we plan to: 1) assess how well the microbial communities in exhaled breath condensate reflect the microbial communities in the lungs and 2) identify the origins (mouth, nose, gut, inspired air) of any microbial communities in exhaled breath condensate not present in the lungs. The ability to characterize the lung microbiome using exhaled breath condensate, alone or paired with other non-invasive samples will open the door to large-scale population-based epidemiology studies that are currently cost-prohibitive and logistically infeasible. We plan to follow this work with future studies of the respiratory microbiome's role in processing inhaled environmental pollutants, predicting survival among patients with severe lung disease, and as a diagnostic for clinical use. Thus, this work is expected to lead to substantial improvements in our understanding of the role of the respiratory microbiome on human health.

 描述（由申请人提供）：细菌普遍存在于整个人体中，存在于与外部环境的所有界面处。这些微生物的数量是人类细胞的十倍，具有高度的生理活性，并且已知会影响宿主的健康。尽管迄今为止大多数研究都集中在皮肤，口咽，胃肠道和阴道的微生物上，但现在人们已经认识到肺部并不像人们曾经认为的那样无菌。事实上，有证据表明，肺部的微生物负担和多样性在健康个体和肺部疾病患者之间存在差异。此外，肺部的微生物组成与呼吸道疾病的严重程度有关。由于已知肠道中的微生物群落可以代谢环境毒物，刺激宿主炎症反应，并增加宿主感染的风险，因此呼吸道微生物可能在人类健康中也起着重要作用。研究呼吸道微生物组的一个主要挑战是在肺部缺乏一种成熟的非侵入性测量方法。支气管肺泡灌洗是测量肺部最直接的方法，但它是在医院镇静下进行的侵入性手术。这使得参与者负担太重，大型临床和流行病学研究的成本过高。为了克服这些局限性，这项探索性研究的目的是系统地研究呼出气冷凝液作为一种新型的非侵入性介质来表征呼吸道微生物组。由于呼出气冷凝液可能反映了几个相互连接的生物区室，我们计划表征从18名健康个体中采集的呼出气冷凝液、支气管肺泡灌洗液、口腔洗液、鼻拭子、粪便和吸入空气样本的并行样本的微生物群落。具体而言，我们计划：1）评估呼出气冷凝物中的微生物群落如何反映肺中的微生物群落，以及2）鉴定呼出气冷凝物中不存在于肺中的任何微生物群落的来源（口、鼻、肠道、吸入空气）。单独使用呼出气冷凝液或与其他非侵入性样本配对来表征肺部微生物组的能力将为目前成本高昂且后勤不可行的大规模基于人群的流行病学研究打开大门。我们计划在未来研究呼吸道微生物组在处理吸入的环境污染物中的作用，预测严重肺部疾病患者的生存率，以及作为临床诊断的研究中继续这项工作。因此，这项工作有望大大提高我们对呼吸道微生物组对人类健康作用的理解。