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儿童哮喘包含具有独特鼻腔微生物群的不同表型簇。

Pediatric asthma comprises different phenotypic clusters with unique nasal microbiotas.

机构信息

Computational Biology Institute, Milken Institute School of Public Health,, George Washington University, Innovation Hall, Suite 305, 45085 University Drive, Ashburn, VA, 20147, USA.

Department of Epidemiology and Biostatistics, Milken Institute School of Public Health, George Washington University, Washington, DC, 20052, USA.

出版信息

Microbiome. 2018 Oct 4;6(1):179. doi: 10.1186/s40168-018-0564-7.

Abstract

BACKGROUND

Pediatric asthma is the most common chronic childhood disease in the USA, currently affecting ~ 7 million children. This heterogeneous syndrome is thought to encompass various disease phenotypes of clinically observable characteristics, which can be statistically identified by applying clustering approaches to patient clinical information. Extensive evidence has shown that the airway microbiome impacts both clinical heterogeneity and pathogenesis in pediatric asthma. Yet, so far, airway microbiotas have been consistently neglected in the study of asthma phenotypes. Here, we couple extensive clinical information with 16S rRNA high-throughput sequencing to characterize the microbiota of the nasal cavity in 163 children and adolescents clustered into different asthma phenotypes.

RESULTS

Our clustering analyses identified three statistically distinct phenotypes of pediatric asthma. Four core OTUs of the pathogenic genera Moraxella, Staphylococcus, Streptococcus, and Haemophilus were present in at least 95% of the studied nasal microbiotas. Phyla (Proteobacteria, Actinobacteria, and Bacteroidetes) and genera (Moraxella, Corynebacterium, Dolosigranulum, and Prevotella) abundances, community composition, and structure varied significantly (0.05 < P ≤ 0.0001) across asthma phenotypes and one of the clinical variables (preterm birth). Similarly, microbial networks of co-occurrence of bacterial genera revealed different bacterial associations across asthma phenotypes.

CONCLUSIONS

This study shows that children and adolescents with different clinical characteristics of asthma also show different nasal bacterial profiles, which is indicative of different phenotypes of the disease. Our work also shows how clinical and microbial information could be integrated to validate and refine asthma classification systems and develop biomarkers of disease.

摘要

背景

小儿哮喘是美国最常见的儿童慢性疾病,目前影响约 700 万儿童。这种异质性综合征被认为包含各种临床可观察特征的疾病表型,可以通过应用聚类方法对患者临床信息进行统计学识别。大量证据表明,气道微生物组影响小儿哮喘的临床异质性和发病机制。然而,到目前为止,气道微生物群在哮喘表型的研究中一直被忽视。在这里,我们将广泛的临床信息与 16S rRNA 高通量测序相结合,对 163 名儿童和青少年的鼻腔微生物组进行了特征描述,这些儿童和青少年聚类成不同的哮喘表型。

结果

我们的聚类分析确定了三种统计学上不同的小儿哮喘表型。致病性属莫拉氏菌、葡萄球菌、链球菌和嗜血杆菌的四个核心 OTU 存在于至少 95%的研究鼻腔微生物群中。门(变形菌门、放线菌门和拟杆菌门)和属(莫拉氏菌属、棒状杆菌属、多尔西格兰氏菌属和普雷沃氏菌属)丰度、群落组成和结构在哮喘表型和临床变量(早产)之间存在显著差异(0.05<P≤0.0001)。同样,细菌属的共生网络显示了哮喘表型之间不同的细菌关联。

结论

这项研究表明,具有不同临床特征的哮喘儿童和青少年也表现出不同的鼻腔细菌谱,这表明疾病存在不同的表型。我们的工作还展示了如何整合临床和微生物信息来验证和细化哮喘分类系统,并开发疾病的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0f0/6172741/97ddbe7ffa36/40168_2018_564_Fig1_HTML.jpg

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