Trinity Centre for Health Science, Clinical Microbiology Department, School of Medicine, Faculty of Health Science, Trinity College Dublin, Tallaght University Hospital, D24 NR0A Dublin, Ireland.
Teagasc Food Research Centre, Moorepark, Fermoy, P61 C996 Co Cork, Ireland.
Int J Mol Sci. 2024 Mar 31;25(7):3893. doi: 10.3390/ijms25073893.
Cystic fibrosis (CF) is an inherited genetic disorder which manifests primarily in airway disease. Recent advances in molecular technologies have unearthed the diverse polymicrobial nature of the CF airway. Numerous studies have characterised the genus-level composition of this airway community using targeted 16S rDNA sequencing. Here, we employed whole-genome shotgun metagenomics to provide a more comprehensive understanding of the early CF airway microbiome. We collected 48 sputum samples from 11 adolescents and children with CF over a 12-month period and performed shotgun metagenomics on the Illumina NextSeq platform. We carried out functional and taxonomic analysis of the lung microbiome at the species and strain levels. Correlations between microbial diversity measures and independent demographic and clinical variables were performed. Shotgun metagenomics detected a greater diversity of bacteria than culture-based methods. A large proportion of the top 25 most-dominant species were anaerobes. Samples dominated by and had significantly higher microbiome diversity, while no CF pathogen was associated with reduced microbial diversity. There was a diverse resistome present in all samples in this study, with 57.8% agreement between shotgun metagenomics and culture-based methods for detection of resistance. Pathogenic sequence types (STs) of , , and were observed to persist in young CF patients, while STs of were both persistent and shared between patients. This study provides new insight into the temporal changes in strain level composition of the microbiome and the landscape of the resistome in young people with CF. Shotgun metagenomics could provide a very useful one-stop assay for detecting pathogens, emergence of resistance and conversion to persistent colonisation in early CF disease.
囊性纤维化（CF）是一种遗传性遗传疾病，主要表现为气道疾病。分子技术的最新进展揭示了 CF 气道的多种多微生物性质。许多研究使用靶向 16S rDNA 测序对该气道群落的属级组成进行了特征描述。在这里，我们采用全基因组鸟枪法宏基因组学来更全面地了解早期 CF 气道微生物组。我们在 12 个月的时间内从 11 名患有 CF 的青少年和儿童中收集了 48 份痰样本，并在 Illumina NextSeq 平台上进行了鸟枪法宏基因组学。我们在种和菌株水平上对肺微生物组进行了功能和分类分析。对微生物多样性措施与独立的人口统计学和临床变量之间的相关性进行了分析。鸟枪法宏基因组学检测到的细菌多样性高于基于培养的方法。排名前 25 位的最主要物种中有很大一部分是厌氧菌。由 和 主导的样本具有显着更高的微生物多样性，而没有 CF 病原体与微生物多样性降低相关。在本研究中，所有样本中都存在多样化的耐药组，鸟枪法宏基因组学和基于培养的方法在检测耐药性方面的一致性为 57.8％。观察到 、 、 和 的致病序列型（ST）在年轻 CF 患者中持续存在，而 的 ST 既持续存在又在患者之间共享。这项研究提供了有关 CF 年轻人微生物组在菌株水平组成和耐药组景观方面的时间变化的新见解。鸟枪法宏基因组学可以为检测病原体，耐药性的出现以及早期 CF 疾病中持续定植的转换提供非常有用的一站式检测方法。
