The cystic fibrosis upper and lower airway metagenome

Chronic airway infections determine the outcome in cystic fibrosis (CF). We wanted to compare the quantitative composition of the upper and lower airway microbiome in mild and severe CF.Whole genome shotgun sequencing was performed on total DNA isolated from nasal lavage, oropharyngeal swab and induced sputum collected from exocrine pancreatic sufficient and exocrine pancreatic insufficient CF children and adults. Metagenomics identified CF disease-associated microbial communities in upper and lower airways, but a normal flora in the oral cavity. CF virome and mycobiome were dominated by phages, Candida and Aspergillus species, respectively. Staphylococcus epidermidis was the most prominent bacterium in the upper airways. Staphylococcus aureus and Pseudomonas aeruginosa were more abundant in lower than in upper airways. Four distinct groups prevailed by either S. aureus, P. aeruginosa, Haemophilus influenzae or anaerobes, could be discerned in the CF sputum of all age groups. Within the Veillonella, Prevotella, Rothia and Streptococcus genera the individual species were not equivalent in their impact on CF airway microbiome and disease. Prevotella melaninogenica was recovered more often and at higher abundance from CF patients with mild disease. The quantitative composition of the CF upper and lower airways microbiome differs by pancreatic status and disease severity.

慢性气道感染决定囊性纤维化（cystic fibrosis, CF）患者的预后。本研究旨在对比轻度与重度囊性纤维化患者上、下气道微生物组的定量组成。研究对来自外分泌胰腺功能正常与外分泌胰腺功能不全的囊性纤维化儿童及成人的鼻腔灌洗液、口咽拭子及诱导痰样本中提取的总DNA开展了全基因组鸟枪法测序（whole genome shotgun sequencing）。宏基因组学（metagenomics）分析显示，囊性纤维化患者的上、下气道存在与疾病相关的微生物群落，而口腔菌群则呈现正常菌群结构。囊性纤维化患者的病毒组（virome）与真菌组（mycobiome）分别以噬菌体（phages）、念珠菌属（Candida）及曲霉属（Aspergillus）物种为主要优势类群。表皮葡萄球菌（Staphylococcus epidermidis）是上气道中最为突出的细菌。金黄色葡萄球菌（Staphylococcus aureus）与铜绿假单胞菌（Pseudomonas aeruginosa）在下气道中的丰度显著高于上气道。在所有年龄组的囊性纤维化患者痰液样本中，均可辨识出四类优势菌群，分别以金黄色葡萄球菌、铜绿假单胞菌、流感嗜血杆菌（Haemophilus influenzae）或厌氧菌为主导。在韦荣球菌属（Veillonella）、普雷沃菌属（Prevotella）、罗氏菌属（Rothia）及链球菌属（Streptococcus）中，不同物种对囊性纤维化气道微生物组及疾病的影响并不等同。黑普雷沃菌（Prevotella melaninogenica）在轻症囊性纤维化患者中更常被检出，且丰度更高。囊性纤维化患者上、下气道微生物组的定量组成差异与胰腺功能状态及疾病严重程度密切相关。