The Lung Tissue Microbiome in Chronic Obstructive Pulmonary Disease
The Lung Tissue Microbiome in Chronic Obstructive Pulmonary Disease
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DOI：
10.1164/rccm.201111-2075oc
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发表时间：
2012-05-15
影响因子：
24.7
通讯作者：
Hogg, James C.
中科院分区：
文献类型：
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作者：
Sze, Marc A.;Dimitriu, Pedro A.;Hogg, James C.
基本原理：Hilty及其同事基于表面刷拭和支气管肺泡灌洗液，证明了哮喘和慢性阻塞性肺疾病（COPD）的人肺特征中的微生物组，这一点现在已被其他人证实。极重度COPD患者（COPD全球倡议[GOLD] 4）（n = 8）;囊性纤维化（CF）患者（n = 8）。后者作为阳性对照，无菌水作为阴性对照。所有细菌群落分析均基于聚合酶链反应扩增16 S rRNA基因片段。通过定量聚合酶链反应测量总细菌种群，通过末端限制性片段长度多态性分析和pyrotag测序评估细菌群落组成。测量和主要结果：肺组织内的总细菌数量较少（每1，000个人体细胞中有20- 1，252个细菌细胞），但所有四个样本组均高于阴性对照组（P < 0.001）。末端限制性片段长度多态性分析和测序区分了三种不同的细菌群落组成：一种是非吸烟者和吸烟者组共有的，第二种是GOLD 4组，第三种是CF阳性对照组。Pyrotag测序鉴定了超过1，400个独特的细菌序列，并显示GOLD 4患者中厚壁菌门的增加与所有其他组相比（P < 0.003），这归因于乳杆菌属的增加（P < 0.0007）。
Rationale: Based on surface brushings and bronchoalveolar lavage fluid, Hilty and coworkers demonstrated microbiomes in the human lung characteristic of asthma and chronic obstructive pulmonary disease (COPD), which have now been confirmed by others.Objectives: To extend these findings to human lung tissue samples.Methods: DNA from lung tissue samples was obtained from nonsmokers (n = 8); smokers without COPD (n = 8); patients with very severe COPD (Global Initiative for COPD [GOLD] 4) (n = 8); and patients with cystic fibrosis (CF) (n = 8). The latter served as a positive control, with sterile water as a negative control. All bacterial community analyses were based on polymerase chain reaction amplifying 16S rRNA gene fragments. Total bacterial populations were measured by quantitative polymerase chain reaction and bacterial community composition was assessed by terminal restriction fragment length polymorphism analysis and pyrotag sequencing.Measurement and Main Results: Total bacterial populations within lung tissue were small (20-1,252 bacterial cells per 1,000 human cells) but greater in all four sample groups versus the negative control group (P < 0.001). Terminal restriction fragment length polymorphism analysis and sequencing distinguished three distinct bacterial community compositions: one common to the nonsmoker and smoker groups, a second to the GOLD 4 group, and the third to the CF-positive control group. Pyrotag sequencing identified greater than 1,400 unique bacterial sequences and showed an increase in the Firmicutes phylum in GOLD 4 patients versus all other groups (P < 0.003) attributable to an increase in the Lactobacillus genus (P < 0.0007).Conclusions: There is a detectable bacterial community within human lung tissue that changes in patients with very severe COPD.