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

 描述(申请人提供)：细菌普遍存在于人体内，存在于与外部环境的所有界面上。这些微生物的数量是人类细胞的10倍，具有高度的生理活性，并已知会影响宿主的健康。尽管到目前为止，大多数研究都集中在皮肤、口咽、胃肠道和阴道的微生物上，但现在人们认识到，肺并不像曾经认为的那样是无菌的。事实上，有证据表明，肺部的微生物负担和多样性在健康人和肺部疾病患者之间是不同的。此外，肺部的微生物组成与呼吸系统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，增加宿主感染的风险，因此呼吸道微生物很可能在人类健康中也发挥着重要作用。研究呼吸道微生物组的一个主要挑战是缺乏一种成熟的、非侵入性的肺部测量方法。支气管肺泡灌洗是测量肺部的最直接方法，但它是在医院镇静下进行的侵入性操作。这使得它对参与者来说负担太大，而且对于大型临床和流行病学研究来说，成本过高。为了克服这些限制，这项探索性研究的目的是系统地研究呼出的呼吸冷凝液作为一种新型的、非侵入性的介质来表征呼吸道微生物群。由于呼出的呼吸冷凝液可能反映了几个相互关联的生物舱，我们计划从18名健康人那里收集呼气冷凝液、支气管肺泡灌洗液、口腔洗涤剂、鼻拭子、粪便和吸入空气样本的同时样本的微生物群落特征。我们计划在这项工作之后，进一步研究呼吸道微生物组在处理吸入的环境污染物、预测严重肺部疾病患者的存活率以及作为临床使用的诊断方法方面的作用。因此，这项工作有望大大改善我们对呼吸道微生物群对人类健康的作用的理解。

 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.