Upper versus lower airway microbiome and metagenome in children with cystic fibrosis and their correlation with lung inflammation
Upper versus lower airway microbiome and metagenome in children with cystic fibrosis and their correlation with lung inflammation
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DOI：
10.1371/journal.pone.0222323
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发表时间：
2019-09-19
期刊：
影响因子：
3.7
通讯作者：
Wang, Gary P.
中科院分区：
文献类型：
--
作者：
Kirst, Mariana E.;Baker, Dawn;Wang, Gary P.
目的探讨囊性纤维化（CF）患儿气道内有复杂的多微生物群落，与肺部疾病进展及抗生素使用相关。在年幼的CF儿童中，咽拭子被广泛用作检测下呼吸道潜在致病微生物的替代方法。然而，上呼吸道和下呼吸道微生物群落之间的关系仍然知之甚少。本研究旨在确定(1)CF患儿口咽微生物组与肺微生物组相似的程度；(2)肺微生物组组成是否与气道炎症相关。方法对21例CF患儿和26例对照组同时进行咽拭子和支气管肺泡灌洗（BAL）检查。使用16S rRNA深度测序分析口咽和肺部微生物群，并与BAL和抗生素暴露中的中性粒细胞计数相关。结果咽部微生物群落与肺部微生物群落独立聚集，且微生物多样性更高（p < 0.001）。CF微生物组与非CF对照组显著不同，在上、下CF气道中都有更高的变形菌群丰度。BAL中性粒细胞计数与肺微生物组的多样性呈负相关，而与丰富度不相关。在CF儿童中，口咽和肺微生物组中都富集了与细菌运动蛋白、双组分系统、鞭毛组装和分泌系统相关的微生物基因，而非CF对照组中则富集了与核酸和蛋白质的合成和代谢相关的基因。结论本研究确定了CF气道中独特的微生物特征，其微生物多样性和代谢功能受到气道炎症的显著影响。这些结果强调了使用咽拭子作为替代物来研究CF儿童下气道微生物组和宏基因组的局限性。
ObjectiveAirways of children with cystic fibrosis (CF) harbor complex polymicrobial communities which correlates with pulmonary disease progression and use of antibiotics. Throat swabs are widely used in young CF children as a surrogate to detect potentially pathogenic microorganisms in lower airways. However, the relationship between upper and lower airway microbial communities remains poorly understood. This study aims to determine (1) to what extent oropharyngeal microbiome resembles the lung microbiome in CF children and (2) if lung microbiome composition correlates with airway inflammation.MethodThroat swabs and bronchoalveolar lavage (BAL) were obtained concurrently from 21 CF children and 26 disease controls. Oropharyngeal and lung microbiota were analyzed using 16S rRNA deep sequencing and correlated with neutrophil counts in BAL and antibiotic exposure.ResultsOropharyngeal microbial communities clustered separately from lung communities and had higher microbial diversity (p < 0.001). CF microbiome differed significantly from non-CF controls, with a higher abundance of Proteobacteria in both upper and lower CF airways. Neutrophil count in the BAL correlated negatively with the diversity but not richness of the lung microbiome. In CF children, microbial genes involved in bacterial motility proteins, two-component system, flagella assembly, and secretion system were enriched in both oropharyngeal and lung microbiome, whereas genes associated with synthesis and metabolism of nucleic acids and protein dominated the non-CF controls.ConclusionsThis study identified a unique microbial profile with altered microbial diversity and metabolic functions in CF airways which is significantly affected by airway inflammation. These results highlight the limitations of using throat swabs as a surrogate to study lower airway microbiome and metagenome in CF children.