Endotracheal virome and metatranscriptome of preterm neonates at birth in relation with progression to bronhopulmonary dysplasia
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Bronchopulmonary dysplasia (BPD) is a major complication of prematurity with unclear pathogenesis. While bacterial dysbiosis has been implicated, the role of the virome remains largely unexplored. We analyzed endotracheal aspirates from 31 very preterm neonates (< 30 weeks gestation) collected within 24 hours of birth using ultra-deep viral metagenomics, 16S rRNA profiling, and metatranscriptomics to assess transcriptionally active bacteria and host responses. A low-abundance individualized virome, including mainly unclassified Caudoviricetes bacteriophages, was detected in 71% of neonates, with greater viral richness in those born vaginally. Multi-Omics Factor Analysis identified four microbial endotypes; one “protective” endotype with low microbial load was associated with reduced BPD risk (29% vs. 79%, p = 0.03), whereas high-risk clusters exhibited increased Pseudomonas load, elevated bacterial transcriptional activity, and greater viral diversity. Longitudinal studies are needed to determine how early viral acquisition shapes microbial endotypes and BPD progression, potentially enabling personalized, microbiome-targeted interventions in preterm neonates.
