Dept of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
Dept of Biostatistics and Bioinformatics and Computational Biology Institute, The George Washington University, Washington, DC, USA.
Eur Respir J. 2022 Jul 13;60(1). doi: 10.1183/13993003.02293-2021. Print 2022 Jul.
Bronchiolitis is not only the leading cause of hospitalisation in US infants but also a major risk factor for asthma development. Growing evidence supports clinical heterogeneity within bronchiolitis. Our objectives were to identify metatranscriptome profiles of infant bronchiolitis, and to examine their relationship with the host transcriptome and subsequent asthma development.
As part of a multicentre prospective cohort study of infants (age <1 year) hospitalised for bronchiolitis, we integrated virus and nasopharyngeal metatranscriptome (species-level taxonomy and function) data measured at hospitalisation. We applied network-based clustering approaches to identify metatranscriptome profiles. We then examined their association with the host transcriptome at hospitalisation and risk for developing asthma.
We identified five metatranscriptome profiles of bronchiolitis (n=244): profile A: virusmicrobiome; profile B: virusmicrobiome ; profile C: virusmicrobiome ; profile D: virusmicrobiome ; and profile E: virusmicrobiome . Compared with profile A, profile B infants were characterised by a high proportion of eczema, abundance and enriched virulence related to antibiotic resistance. These profile B infants also had upregulated T-helper 17 and downregulated type I interferon pathways (false discovery rate (FDR) <0.005), and significantly higher risk for developing asthma (17.9% 38.9%; adjusted OR 2.81, 95% CI 1.11-7.26). Likewise, profile C infants were characterised by a high proportion of parental asthma, dominance, and enriched glycerolipid and glycerophospholipid metabolism of the microbiome. These profile C infants had an upregulated RAGE signalling pathway (FDR <0.005) and higher risk of asthma (17.9% 35.6%; adjusted OR 2.49, 95% CI 1.10-5.87).
Metatranscriptome and clustering analysis identified biologically distinct metatranscriptome profiles that have differential risks of asthma.
细支气管炎不仅是美国婴儿住院的主要原因，也是哮喘发展的主要危险因素。越来越多的证据支持细支气管炎的临床异质性。我们的目标是确定婴儿细支气管炎的宏转录组谱，并研究其与宿主转录组和随后的哮喘发展的关系。
作为一项针对因细支气管炎住院的婴儿（<1 岁）的多中心前瞻性队列研究的一部分，我们整合了病毒和鼻咽宏转录组（种级分类和功能）数据，这些数据是在住院时测量的。我们应用基于网络的聚类方法来识别宏转录组谱。然后，我们研究了它们与住院时宿主转录组的关联以及发展为哮喘的风险。
我们确定了细支气管炎的五种宏转录组谱（n=244）：谱 A：病毒微生物组；谱 B：病毒微生物组；谱 C：病毒微生物组；谱 D：病毒微生物组；谱 E：病毒微生物组。与谱 A 相比，谱 B 婴儿的特征是湿疹比例高，丰度高，与抗生素耐药性相关的病毒毒力增强。这些谱 B 婴儿还表现出 Th17 途径上调和 I 型干扰素途径下调（错误发现率（FDR）<0.005），并且哮喘发病风险显著增加（17.9% 38.9%；调整后的 OR 2.81，95% CI 1.11-7.26）。同样，谱 C 婴儿的特征是父母哮喘比例高，微生物组中甘油脂和甘油磷脂代谢占主导地位。这些谱 C 婴儿的 RAGE 信号通路上调（FDR<0.005），哮喘发病风险更高（17.9% 35.6%；调整后的 OR 2.49，95% CI 1.10-5.87）。
宏转录组和聚类分析确定了具有不同哮喘风险的生物学上不同的宏转录组谱。
