Abstract

The question addressed by the study: Bronchiolitis is not only the leading cause of hospitalisation in U.S. infants but also a major risk factor for asthma development. Growing evidence supports clinical heterogeneity within bronchiolitis. To identify metatranscriptome profiles of infant bronchiolitis, and examine their relationship with host transcriptome and subsequent asthma development. Materials/patients and methods: As part of multicentre prospective cohort study of infants (age <12 months) 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 host transcriptome at hospitalisation and risk for developing asthma. Results: We identified five metatranscriptome profiles of bronchiolitis (n=244):A) virusRSVmicrobiomecommensals, B) virusRSV/RV-Amicrobiome H.influenzae ,C) virusRSVmicrobiome S.pneumoniae , D) virusRSVmicrobiome M.nonliquefaciens, andE) virusRSV/RV-Cmicrobiome M.catarrhalis . Compared with profile A, profile B infants were characterised by high proportion of eczema, H. influenzae abundance, and enriched virulence related to antibiotic resistance. These profile B infants also had upregulated TH17 and downregulated type I interferon pathways (FDR<0.005) and significantly higher risk for developing asthma (17.9% versus 38.9%; adjOR, 2.81; 95%CI, 1.11-7.26). Likewise, profile C infants were characterised by high proportion of parental asthma, S. pneumoniae dominance, and enriched glycerolipid and glycerophospholipid metabolism of microbiome. These profile C infants had upregulated receptor for advanced glycation end products signalling pathway (FDR<0.005) and higher risk of asthma (17.9% versus 35.6%; adjOR, 2.49; 95%CI, 1.10-5.87). Answer to the question: Metatranscriptome and clustering analysis identified biologically-distinct metatranscriptome profiles that have differential risks of asthma.