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Insights into the relationship between nasal bacterial composition and susceptibility to early-life respiratory disease: a pilot observational study.

Caparros-Martin, J. A.; Kicic-Starcevich, E.; Agudelo-Romero, P.; Hancock, D. G.; Iosifidis, T.; Karpievitch, Y. V.; Martino, D. J.; Zhang, G.; Silva, D. T.; Bosco, A.; Prescott, S. L.; LeSouef, P.; Kicic, A.; Stick, S.

2025-08-19 respiratory medicine
10.1101/2025.08.16.25333459 medRxiv
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BackgroundEarly-life susceptibility to viral respiratory infections is associated with long-term respiratory morbidity in children. Currently, no reliable tools exist to predict susceptibility to these infections. Given its role in modulating pathogen virulence and airway inflammation, the endogenous microbiota represents a potential target for prevention. In this pilot study, we investigated whether distinct nasal microbial communities are associated with viral respiratory disease and respiratory phenotypes during the first year of life. MethodsWe analyzed 90 nasal swabs from 55 infants enrolled in the AERIAL study, representing background samples collected at schedule visits ([~]4 months old) and samples from symptomatic episodes. Bacterial profiling was done blinded to clinical data via full-length 16S rRNA sequencing, and bacterial load was quantified using a pan-bacterial TaqMan(R) assay. ResultsNasal bacterial diversity was similar between background and symptomatic swabs, with community composition differences largely driven by inter-individual variation. In paired samples, symptomatic swabs showed reduced diversity but no change in bacterial load. Virus-bacteria interactions were observed in rhinovirus-positive swabs, but not in SARS-CoV-2-positive swabs. Two distinct bacterial endotypes were identified, enriched in either Moraxella or Streptococcus species and differing in alpha diversity. In background swabs, microbial endotypes were not associated with the number of symptomatic swabs or bronchiolitis episodes. We observed a potential sex-specific association between background swabs endotypes and number of wheezing episodes, which warrants further investigation in follow-up studies. ConclusionOur pilot data suggest that the nasal microbiota might influence wheezing outcomes in a sex-specific manner, highlighting the need for larger, longitudinal investigations.

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