Direct Lung Sampling Indicates That Established Pathogens Dominate Early Infections in Children with Cystic Fibrosis

Direct Lung Sampling Indicates That Established Pathogens Dominate Early Infections in Children with Cystic Fibrosis
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DOI:
10.1016/j.celrep.2019.03.086
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发表时间:
2019-04-23
期刊:
影响因子:
8.8
通讯作者:
Singh, Pradeep K.
Singh, Pradeep K.
中科院分区:
生物学1区
文献类型:
--
作者:
Jorth, Peter;Ehsan, Zarmina;Singh, Pradeep K.

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培养和测序产生了关于囊性纤维化(CF)肺部感染的不同假设。培养表明,CF 肺部在被有限的 CF 病原体定植之前并未受到感染。测序表明,大多数口腔细菌的不同群落早期就栖息在肺部,并且随着疾病的进展,多样性逐渐减少。我们通过支气管镜检查和测序研究了 CF 儿童的肺部微生物群,并采取了减少污染的措施。我们没有发现肺灌洗液中口腔细菌群落缺乏 CF 病原体的证据。灌洗液微生物多样性差异很大,但多样性下降似乎是由 CF 病原体丰度增加导致的,这减少了污染物的信号。在一些含有 CF 病原体的灌洗液中检测到链球菌、普雷沃氏菌和韦荣氏菌 DNA,但这些生物体的 DNA 远远超过 CF 病原体 DNA,并且与炎症无关。这些发现支持这样的假设:已确定的 CF 病原体是 CF 肺部感染的主要原因。
Culture and sequencing have produced divergent hypotheses about cystic fibrosis (CF) lung infections. Culturing suggests that CF lungs are uninfected before colonization by a limited group of CF pathogens. Sequencing suggests diverse communities of mostly oral bacteria inhabit lungs early on and diversity decreases as disease progresses. We studied the lung microbiota of CF children using bronchoscopy and sequencing, with measures to reduce contamination. We found no evidence for oral bacterial communities in lung lavages that lacked CF pathogens. Lavage microbial diversity varied widely, but decreases in diversity appeared to be driven by increased CF pathogen abundance, which reduced the signal from contaminants. Streptococcus, Prevotella, and Veillonella DNA was detected in some lavages containing CF pathogens, but DNA from these organisms was vastly exceeded by CF pathogen DNA and was not associated with inflammation. These findings support the hypothesis that established CF pathogens are primarily responsible for CF lung infections.