Study of the Lung Microbiome. Have We Reached the End of the Beginning?
Study of the Lung Microbiome. Have We Reached the End of the Beginning?
复制标题
肺微生物组的研究。
DOI：
10.1164/rccm.201608-1635ed
复制
发表时间：
2017
影响因子：
24.7
通讯作者：
Flores,SoniaC
中科院分区：
文献类型：
--
作者：
Morris,Alison;Flores,SoniaC
由于历史上人们相信肺部是无菌的，因此对肺部微生物组的研究落后于其他身体部位的研究。应用非培养测序技术的初步研究表明，下呼吸道具有可检测的微生物种群，这些微生物种群可能在疾病中发生改变 (1-4)。一些首批有组织的肺部微生物组检查工作是在 HIV 感染者中进行的 (5-7)。这些研究主要针对未经历急性肺部并发症的门诊患者，并明确排除肺炎患者来研究健康个体的微生物组。由于持续的先天性和后天性免疫缺陷，艾滋病毒感染者仍然面临细菌性肺炎的风险，即使接受抗逆转录病毒治疗，最近人们对急性肺炎背景下艾滋病毒肺部微生物组的改变产生了兴趣。低收入和中等收入国家承担着不成比例的细菌性肺炎负担，肺部感染是乌干达艾滋病毒感染的常见且经常致命的并发症，Shenoy 及其同事在本期杂志上发表了这项研究（第 104-114 页）(8)。由于非洲艾滋病毒感染人群获得抗逆转录病毒药物的机会较少，结核病等合并感染的负担较高，因此因肺炎住院后的死亡风险增加，因此了解肺微生物组在这种情况下的作用非常重要，作为改变肺炎风险和结果的潜在工具。 Shenoy 及其同事当前的研究扩展了之前针对艾滋病毒感染者肺炎人群的研究，对来自乌干达的一大群接受支气管镜检查的急性肺炎患者进行了检查 (8)。除了揭示特别是艾滋病毒肺炎期间肺部细菌群落之外，这项工作还因其对肺部微生物组领域的更广泛影响而具有重要意义。这项工作使我们超越了主要使用基于 16S rRNA 的分类方法的肺微生物组研究的最初努力。当前的研究使用复杂的生物信息学来识别入组患者中不同的微生物群落状态（MCS），并确定这些群落与功能结果的关系。通过整合微生物组、宿主基因表达、代谢组学和临床结果，并通过研究细菌和其他生物体之间的关系，本研究展示了如何超越简单的细菌描述，并提出了基于微生物失调定制治疗的可能性。不同微生物群落状态或肺微生物组“表型”的发现对于艾滋病毒感染肺炎患者群体来说是新颖的。该研究确定了一个以假单胞菌科、鞘氨醇单胞菌科和普氏菌科为主的 MCS1 微生物群落，以及一个以链球菌科 (MCS2A) 或普氏菌科 (MCS2B) 呈倒数梯度的第二个 MCS2 微生物群落。群落状态在细菌和其他生物体之间的关系方面有所不同，MCS1 个体中分枝杆菌阳性培养物的比例很高，而 MCS2B 个体中曲霉属阳性培养物的比例很高。
Studies of the lung microbiome have lagged behind those of other body sites because of the historical belief that the lungs were sterile. Initial studies applying non–culture-based sequencing techniques demonstrated that the lower respiratory tract has a detectable microbial population that may be altered in disease (1–4). Some of the first organized efforts to examine the lung microbiome were performed in HIV-infected individuals (5–7). These studies primarily focused on outpatients who were not experiencing acute pulmonary complications and explicitly excluded individuals with pneumonias to study the microbiome of healthy individuals. Because HIV-infected individuals remain at risk for bacterial pneumonia as a result of persistent innate and acquired immune deficits, even when treated with antiretroviral therapy, there has been recent interest in alterations of the HIV lung microbiome in the setting of acute pneumonia. Low-and middle-income countries shoulder a disproportionate share of the burden of bacterial pneumonia, and pulmonary infection is a common and frequently fatal complication of HIV infection in Uganda, the site of the study published in this issue of the Journal by Shenoy and colleagues (pp. 104–114)(8). As African HIV-infected populations with less access to antiretroviral drugs and higher burden of coinfections such as tuberculosis have an increased risk for mortality after hospitalization for pneumonia, it is important to understand the role of the lung microbiome in this setting as a potential tool to modify pneumonia risk and outcome. The current study by Shenoy and colleagues expands on prior work in the HIV-infected population with pneumonia by examining a large cohort of individuals from Uganda undergoing bronchoscopy for acute pneumonia (8). In addition to shedding light on the bacterial communities in the lung during pneumonia in HIV in particular, the work is important for its broader implications for the field of the lung microbiome in general. The work takes us beyond the initial efforts in lung microbiome studies that have primarily used 16S rRNA-based taxonomic approaches. The current study used sophisticated bioinformatics to identify distinct microbial community states (MCS) in the enrolled patients and determined the relationship of these communities to functional outcomes. By integrating the microbiome, host gene expression, metabolomics, and clinical outcomes, and by investigating the relationships between bacteria and other organisms, this study demonstrates how to move beyond simple bacterial description and raises the possibility of tailoring therapies based on microbial dysbiosis.The discovery of different microbial community states or “phenotypes” of the lung microbiome is novel in this population of HIV-infected patients with pneumonia. The study identified an MCS1 microbial community that was dominated by Pseudomonadaceae in conjunction with Sphingomonadaceae and Prevotellaceae, and a second MCS2 community that exhibited a reciprocal gradient of Streptococcaceae (MCS2A) or Prevotellaceae (MCS2B). The community states differed in relationships between bacteria and other organisms with a high proportion of Mycobacterium-positive cultures in MCS1 and Aspergillus-positive cultures in MCS2B individuals.