Longitudinal analysis of the lung microbiome in lung transplantation

Longitudinal analysis of the lung microbiome in lung transplantation
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DOI:
10.1111/1574-6968.12053
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发表时间:
2013-02-01
影响因子:
2.1
通讯作者:
Isaacson, Richard E.
Isaacson, Richard E.
中科院分区:
生物学4区
文献类型:
--
作者:
Borewicz, Klaudyna;Pragman, Alexa A.;Isaacson, Richard E.

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肺移植受者的长期存活率很低,这主要是由于慢性排斥反应。慢性排斥的发病机制尚不完全清楚,但肺部细菌定植与慢性排斥有关,而抗生素的使用减缓了慢性排斥的进展。肺部有一个细菌群落,称为微生物群,在健康和疾病中都存在。我们假设移植后肺微生物群会发生变化,这些变化可能与排斥反应的发生发展相对应。4例患者于移植后3个时间点采集12份支气管肺泡灌洗液(BALF),2份来自健康对照。通过对16S rRNA基因高变区3进行焦糖测序,确定每个样品的微生物组。使用Mothur、核糖体数据库项目分类器、Fast UniFrac和Metastats分析数据。与对照肺相比,移植肺含有更多的细菌序列,并显示出更多的微生物多样性。移植样本中以变形杆菌门(贝塔蛋白细菌纲)中的细菌为主。相比之下,健康肺的微生物群由变形杆菌门(伽马蛋白细菌纲)和微生物群组成。移植肺的微生物组与健康肺的微生物组有很大的不同,主要是由于移植标本中存在伯克霍尔德里亚科。
Lung transplant recipients experience poor long-term survival, largely due to chronic rejection. The pathogenesis of chronic rejection is incompletely understood, but bacterial colonization of the lung is associated with chronic rejection, while antibiotic use slows its progression. The lung harbors a bacterial community, termed the microbiome, which is present both in health and disease. We hypothesize that the lung microbiome will change following transplantation, and these changes may correspond to the development of rejection. Twelve bronchoalveolar lavage fluid (BALF) samples were obtained from four patients at three time points after transplantation, and two BALF samples were obtained from healthy, nontransplant controls. The microbiome of each sample was determined by pyrosequencing the 16S rRNA gene hypervariable 3 region. The data were analyzed using mothur, Ribosomal Database Project Classifier, Fast UniFrac, and Metastats. Transplanted lungs contained more bacterial sequences and demonstrated more microbial diversity than did control lungs. Bacteria in the phyla Proteobacteria (class Betaproteobacteria) predominated in the transplant samples. In contrast, the microbiome of the healthy lung consisted of the phyla Proteobacteria (class Gammaproteobacteria) and Firmicutes. The microbiome of the transplanted lung is vastly different from that of healthy lungs, mainly due to the presence of the family Burkholderiaceae in transplant samples.