摘要

BACKGROUND:Asthmatic patients have higher microbiome diversity and an altered composition, with more Proteobacteria and less Bacteroidetes compared with healthy control subjects. Studies comparing airway inflammation and the airway microbiome are sparse, especially in subjects not receiving anti-inflammatory treatment.
OBJECTIVE:We sought to describe the relationship between the airway microbiome and patterns of airway inflammation in steroid-free patients with asthma and healthy control subjects.
METHODS:Bronchoalveolar lavage fluid was collected from 23 steroid-free nonsmoking patients with asthma and 10 healthy control subjects. Bacterial DNA was extracted from and subjected to Illumina MiSeq sequencing of the 16S rDNA V4 region. Eosinophils and neutrophils in the submucosa were quantified by means of immunohistochemical identification and computerized image analysis. Induced sputum was obtained, and airway hyperresponsiveness to mannitol and fraction of exhaled nitric oxide values were measured. Relationships between airway microbial diversity and composition and inflammatory profiles were analyzed.
RESULTS:In asthmatic patients airway microbial composition was associated with airway eosinophilia and AHR to mannitol but not airway neutrophilia. The overall composition of the airway microbiome of asthmatic patients with the lowest levels of eosinophils but not asthmatic patients with the highest levels of eosinophils deviated significantly from that of healthy subjects. Asthmatic patients with the lowest levels of eosinophils had an altered bacterial abundance profile, with more Neisseria, Bacteroides, and Rothia species and less Sphingomonas, Halomonas, and Aeribacillus species compared with asthmatic patients with more eosinophils and healthy control subjects.
CONCLUSION:The level of eosinophilic airway inflammation correlates with variations in the microbiome across asthmatic patients, whereas neutrophilic airway inflammation does not. This warrants further investigation on molecular pathways involved in both patients with eosinophilic and those with noneosinophilic asthma.

译文

背景: 与健康对照组相比，哮喘患者的微生物组多样性更高，组成也发生了变化，变形杆菌更多，拟杆菌更少。比较气道炎症和气道微生物组的研究很少，尤其是在没有接受抗炎治疗的受试者中。
目的: 我们试图描述气道微生物组和气道炎症模式之间的关系，在无激素的哮喘患者和健康的对照组。
方法: 收集 23 例无类固醇吸烟的哮喘患者和 10 例健康对照者的支气管肺泡灌洗液。从 16S srdna V4 区的 Illumina MiSeq 测序中提取细菌 DNA。通过免疫组织化学鉴定和计算机图像分析对粘膜下层的嗜酸性粒细胞和中性粒细胞进行定量。获得诱导痰，并测量气道对甘露醇的高反应性和呼出一氧化氮值的分数。分析了气道微生物多样性与组成和炎症谱之间的关系。
结果: 在哮喘患者中，气道微生物组成与气道嗜酸性粒细胞增多和 AHR 相关，与甘露醇相关，而与气道中性粒细胞增多无关。嗜酸性粒细胞水平最低的哮喘患者而不是嗜酸性粒细胞水平最高的哮喘患者的气道微生物组的总体组成明显偏离健康受试者。嗜酸性粒细胞水平最低的哮喘患者的细菌丰度发生了变化，有更多的奈瑟氏菌、拟杆菌和罗氏菌种类，更少的鞘氨醇单胞菌、盐单胞菌, 与嗜酸性粒细胞较多的哮喘患者和健康对照者相比。
结论: 哮喘患者的嗜酸性粒细胞气道炎症水平与微生物组的变化相关，而中性粒细胞气道炎症则无关。这值得进一步研究嗜酸性粒细胞和非嗜酸性粒细胞哮喘患者的分子通路。