Quantitative analysis of the human airway microbial ecology reveals a pervasive signature for cystic fibrosis.
Quantitative analysis of the human airway microbial ecology reveals a pervasive signature for cystic fibrosis.
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DOI：
10.1126/scitranslmed.3004458
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发表时间：
2012-09-26
影响因子：
17.1
通讯作者：
Quake SR
中科院分区：
文献类型：
--
作者：
Blainey PC;Milla CE;Cornfield DN;Quake SR
囊性纤维化（CF）是一种常染色体隐性遗传疾病，由编码CF跨膜传导调节因子的基因突变引起。粘膜表面电解质稳态的破坏导致严重的肺、胰腺、肠、肝和生殖异常。慢性肺病导致的肺功能丧失是CF死亡的主要原因。使用高通量测序来调查16名CF患者和9名对照个体的痰液中的微生物，我们在健康样本中鉴定了不同的微生物群落，这与健康气道没有显着定植的传统观念相违背。将这些群落与CF患者的群落进行比较，发现微生物生态学存在显著差异，包括未培养的细菌类型的差异表达。尽管存在患者特异性差异，但我们的分析揭示了CF的局部微生物特征。即使排除了经典的CF病原体，病例组和对照组的特征也是不同的。作为对照，还处理了来自一组患有肺部疾病的患者的肺外植体组织。肺组织中的发现证实了痰液样本中鉴定的分类群的存在。将测序结果与临床数据进行比较表明，在我们的成人CF队列中，微生物多样性的减少与肺部炎症的严重程度相关。
Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the gene encoding the CF transmembrane conductance regulator. Disruption of electrolyte homeostasis at mucosal surfaces leads to severe lung, pancreatic, intestinal, hepatic, and reproductive abnormalities. Loss of lung function as a result of chronic lung disease is the primary cause of death from CF. Using high-throughput sequencing to survey microbes in the sputum of 16 CF patients and 9 control individuals, we identified diverse microbial communities in the healthy samples, contravening conventional wisdom that healthy airways are not significantly colonized. Comparing these communities with those from the CF patients revealed significant differences in microbial ecology, including differential representation of uncultivated phylotypes. Despite patient-specific differences, our analysis revealed a focal microbial profile characteristic of CF. The profile differentiated case and control groups even when classically recognized CF pathogens were excluded. As a control, lung explant tissues were also processed from a group of patients with pulmonary disease. The findings in lung tissue corroborated the presence of taxa identified in the sputum samples. Comparing the sequencing results with clinical data indicated that diminished microbial diversity is associated with severity of pulmonary inflammation within our adult CF cohort.
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