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病毒感染后慢性阻塞性肺疾病气道微生物组的衍生。

Outgrowth of the bacterial airway microbiome after rhinovirus exacerbation of chronic obstructive pulmonary disease.

机构信息

1 National Heart and Lung Institute, Imperial College, London, United Kingdom.

出版信息

Am J Respir Crit Care Med. 2013 Nov 15;188(10):1224-31. doi: 10.1164/rccm.201302-0341OC.

DOI:10.1164/rccm.201302-0341OC
PMID:23992479
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3863728/
Abstract

RATIONALE

Rhinovirus infection is followed by significantly increased frequencies of positive, potentially pathogenic sputum cultures in chronic obstructive pulmonary disease (COPD). However, it remains unclear whether these represent de novo infections or an increased load of organisms from the complex microbial communities (microbiome) in the lower airways.

OBJECTIVES

To investigate the effect of rhinovirus infection on the airway bacterial microbiome.

METHODS

Subjects with COPD (n = 14) and healthy control subjects with normal lung function (n = 17) were infected with rhinovirus. Induced sputum was collected at baseline before rhinovirus inoculation and again on Days 5, 15, and 42 after rhinovirus infection and DNA was extracted. The V3-V5 region of the bacterial 16S ribosomal RNA gene was amplified and pyrosequenced, resulting in 370,849 high-quality reads from 112 of the possible 124 time points.

MEASUREMENTS AND MAIN RESULTS

At 15 days after rhinovirus infection, there was a sixfold increase in 16S copy number (P = 0.007) and a 16% rise in numbers of proteobacterial sequences, most notably in potentially pathogenic Haemophilus influenzae (P = 2.7 × 10(-20)), from a preexisting community. These changes occurred only in the sputum microbiome of subjects with COPD and were still evident 42 days after infection. This was in contrast to the temporal stability demonstrated in the microbiome of healthy smokers and nonsmokers.

CONCLUSIONS

After rhinovirus infection, there is a rise in bacterial burden and a significant outgrowth of Haemophilus influenzae from the existing microbiota of subjects with COPD. This is not observed in healthy individuals. Our findings suggest that rhinovirus infection in COPD alters the respiratory microbiome and may precipitate secondary bacterial infections.

摘要

背景

鼻病毒感染后,慢性阻塞性肺疾病(COPD)患者的痰培养阳性率和潜在致病率显著升高。然而,目前尚不清楚这些是否代表新的感染,还是下呼吸道复杂微生物群落(微生物组)中微生物负荷的增加。

目的

研究鼻病毒感染对气道细菌微生物组的影响。

方法

将 COPD 患者(n=14)和肺功能正常的健康对照者(n=17)感染鼻病毒。在鼻病毒接种前的基线时和鼻病毒感染后第 5、15 和 42 天收集诱导痰,提取 DNA。扩增细菌 16S 核糖体 RNA 基因的 V3-V5 区,并进行焦磷酸测序,从 124 个可能的时间点中获得了 370849 个高质量的读数。

测量和主要结果

鼻病毒感染后 15 天,16S 拷贝数增加了六倍(P=0.007),变形菌门序列数量增加了 16%,尤其是潜在致病性流感嗜血杆菌(P=2.7×10(-20)),来自于预先存在的群落。这些变化仅发生在 COPD 患者的痰微生物组中,并且在感染后 42 天仍存在。这与健康吸烟者和不吸烟者微生物组表现出的时间稳定性形成了对比。

结论

鼻病毒感染后,COPD 患者的细菌负荷增加,流感嗜血杆菌从现有的微生物群中大量生长。这在健康个体中并未观察到。我们的研究结果表明,鼻病毒感染 COPD 会改变呼吸道微生物组,并可能引发继发性细菌感染。

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