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囊性纤维化气道中长达十年的细菌群落动态。

Decade-long bacterial community dynamics in cystic fibrosis airways.

机构信息

Department of Pediatrics and Communicable Diseases, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

出版信息

Proc Natl Acad Sci U S A. 2012 Apr 10;109(15):5809-14. doi: 10.1073/pnas.1120577109. Epub 2012 Mar 26.

Abstract

The structure and dynamics of bacterial communities in the airways of persons with cystic fibrosis (CF) remain largely unknown. We characterized the bacterial communities in 126 sputum samples representing serial collections spanning 8-9 y from six age-matched male CF patients. Sputum DNA was analyzed by bar-coded pyrosequencing of the V3-V5 hypervariable region of the 16S rRNA gene, defining 662 operational taxonomic units (OTUs) from >633,000 sequences. Bacterial community diversity decreased significantly over time in patients with typically progressive lung disease but remained relatively stable in patients with a mild lung disease phenotype. Antibiotic use, rather than patient age or lung function, was the primary driver of decreasing diversity. Interpatient variability in community structure exceeded intrapatient variability in serial samples. Antibiotic treatment was associated with pronounced shifts in community structure, but communities showed both short- and long-term resilience after antibiotic perturbation. There was a positive correlation between OTU occurrence and relative abundance, with a small number of persistent OTUs accounting for the greatest abundance. Significant changes in community structure, diversity, or total bacterial density at the time of pulmonary exacerbation were not observed. Despite decreasing community diversity in patients with progressive disease, total bacterial density remained relatively stable over time. These findings show the critical relationship between airway bacterial community structure, disease stage, and clinical state at the time of sample collection. These features are the key parameters with which to assess the complex ecology of the CF airway.

摘要

气道中囊性纤维化(CF)患者的细菌群落结构和动态在很大程度上仍不清楚。我们对 6 名年龄匹配的 CF 男性患者的 126 个痰液样本进行了研究,这些样本代表了 8-9 年的连续采集。通过对 16S rRNA 基因 V3-V5 高变区的条形码焦磷酸测序分析了痰液 DNA,从超过 633,000 个序列中定义了 662 个操作分类单元(OTU)。在通常具有进行性肺病的患者中,细菌群落多样性随时间显著降低,但在具有轻度肺病表型的患者中相对稳定。抗生素的使用而不是患者年龄或肺功能是多样性降低的主要驱动因素。患者间群落结构的变异性大于连续样本中患者内的变异性。抗生素治疗与群落结构的显著变化有关,但在抗生素扰动后,群落表现出短期和长期的恢复力。OTU 的出现与相对丰度呈正相关,少数持久的 OTU 占最大丰度。在肺部恶化时未观察到群落结构、多样性或总细菌密度的显著变化。尽管进行性疾病患者的群落多样性降低,但总细菌密度随时间保持相对稳定。这些发现表明气道细菌群落结构、疾病阶段和采集样本时临床状态之间存在关键关系。这些特征是评估 CF 气道复杂生态的关键参数。

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