Divergence of bacterial communities in the lower airways of CF patients in early childhood.

Divergence of bacterial communities in the lower airways of CF patients in early childhood.
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儿童早期 CF 患者下呼吸道细菌群落的分化。

DOI:
10.1371/journal.pone.0257838
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发表时间:
2021
期刊:
影响因子:
3.7
通讯作者:
Laguna TA
Laguna TA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
O'Connor JB;Mottlowitz MM;Wagner BD;Boyne KL;Stevens MJ;Robertson CE;Harris JK;Laguna TA

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慢性呼吸道感染和炎症导致进行性阻塞性肺疾病是囊性纤维化发病率和死亡率的主要原因。了解不同年龄段的下呼吸道微生物区系可以提供有价值的洞察力和潜在的治疗靶点。描述和比较囊性纤维化和疾病对照受试者在整个儿科年龄段的下呼吸道微生物区系。收集191例(63例囊性纤维化)0~21岁受试者的支气管肺泡灌洗液标本及相关临床资料。我们用定量聚合酶链式反应测量细菌总负荷,并进行16S rRNA基因测序,以表征具有物种水平敏感性的细菌群落。并进行临床对比研究。囊性纤维化样本具有较高的总细菌负荷和较低的微生物多样性,在2-5岁左右偏离疾病对照组,以及相对于细菌负荷的更高的中性粒细胞炎症。在老年人中,囊性纤维化样本中传统囊性纤维化病原体的丰度增加,而中型链球菌种群的丰度降低。有趣的是,异质性疾病对照中增加的多样性与诊断和适应症无关。测序比培养更敏感,抗生素暴露在疾病对照组中更常见,这与负荷和中性粒细胞炎症呈负相关。对不同年龄段的囊性纤维化患者和疾病对照组的下呼吸道样本进行分析,发现了呼吸道微生物区系和炎症的关键差异。儿童早期受试者的差异可能代表着干预和额外研究的机会之窗。
Chronic airway infection and inflammation resulting in progressive, obstructive lung disease is the leading cause of morbidity and mortality in cystic fibrosis. Understanding the lower airway microbiota across the ages can provide valuable insight and potential therapeutic targets. To characterize and compare the lower airway microbiota in cystic fibrosis and disease control subjects across the pediatric age spectrum. Bronchoalveolar lavage fluid samples from 191 subjects (63 with cystic fibrosis) aged 0 to 21 years were collected along with relevant clinical data. We measured total bacterial load using quantitative polymerase chain reaction and performed 16S rRNA gene sequencing to characterize bacterial communities with species-level sensitivity for select genera. Clinical comparisons were investigated. Cystic fibrosis samples had higher total bacterial load and lower microbial diversity, with a divergence from disease controls around 2–5 years of age, as well as higher neutrophilic inflammation relative to bacterial burden. Cystic fibrosis samples had increased abundance of traditional cystic fibrosis pathogens and decreased abundance of the Streptococcus mitis species group in older subjects. Interestingly, increased diversity in the heterogeneous disease controls was independent of diagnosis and indication. Sequencing was more sensitive than culture, and antibiotic exposure was more common in disease controls, which showed a negative relationship with load and neutrophilic inflammation. Analysis of lower airway samples from people with cystic fibrosis and disease controls across the ages revealed key differences in airway microbiota and inflammation. The divergence in subjects during early childhood may represent a window of opportunity for intervention and additional study.
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