ORIGINAL RESEARCH article

Front. Immunol.

Sec. Microbial Immunology

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1605286

Comprehensive analysis of the nasopharyngeal microbiome and host transcriptome in children with varying severity of respiratory syncytial virus infection

Provisionally accepted
Lin  DongLin Dong*Leying  WangLeying WangHaiyan  LiHaiyan LiZhenwei  LiuZhenwei LiuTing  ZhaoTing ZhaoXiaofang  ChenXiaofang ChenPeining  LiuPeining Liu
  • Department of Pediatrics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China

The final, formatted version of the article will be published soon.

The majority of children hospitalized with severe respiratory syncytial virus (RSV) infection do not exhibit conventional identifiable risk factors. The composition of the respiratory microbiota, in conjunction with host factors, significantly influences the initiation and progression of respiratory tract infections.We hypothesized that the severity of RSV infection in children is influenced by the interplay between host immune response regulation and the respiratory microbiota.Methods: 16S rRNA sequencing was conducted on nasopharyngeal aspirate samples from pediatric RSV-infected patients (n = 129) and healthy controls (HCs; n = 21).Leukocyte transcriptomics was conducted using whole blood samples from 75 RSV-infected children and 40 age-matched HCs. Patients were grouped by severity of illness. To identify pathologic regulatory mechanisms, advanced computational methods were employed to analyze and integrate these datasets.Results: Compared with HCs, RSV-infected children exhibited decreased microbial diversity, and higher relative abundances of the genera Pseudomonas, Achromobacter, and Variovorax that were positively correlated with the severity of infection.Transcriptomics uncovered 1,016 differentially expressed genes (DEGs) in the mild-, moderate-, and severe-infection groups versus the HC group. Of these, the 169 DEGs were common to all three infection groups were mainly enriched in processes related to hydrogen peroxide catabolic precursors, host entry mechanisms, response to lipopolysaccharide, and receptor-mediated endocytosis of viruses by host cells.Integrated microbiome and transcriptome analyses revealed strong correlations between two characteristic genera and two genes in the severe group .The respiratory microbiota is useful to distinguish severity of infection. Specifically, interactions between RSV and nasal microbes may regulate the host immune response, potentially affecting the severity of clinical diseases.

Keywords: respiratory syncytial virus, host-microbiota interactions, host transcriptome, RNA, Disease Severity, RNA-Seq

Received: 03 Apr 2025; Accepted: 04 Jul 2025.

Copyright: © 2025 Dong, Wang, Li, Liu, Zhao, Chen and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Lin Dong, Department of Pediatrics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, China

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