Background Early-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.

Methods We 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® assay.

Results Nasal 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.

Conclusion Our pilot data suggest that the nasal microbiota might influence wheezing outcomes in a sex-specific manner, highlighting the need for larger, longitudinal investigations.

AB is a co-founder, equity holder, and director of the startup company Respiradigm Pty Ltd that is related to this work. AB is the founder of the startup company INSiGENe Pty Ltd that is unrelated to this work. No other authors have conflict of interest to disclose.

S.M.S. received funding from the National Health and Medical Research Council (project grant number NHMRC115648) to support the AERIAL study and is also recipient of a NHMRC Investigator grant (NHMRC 2007725). A.K. is a Rothwell Family Fellow. T.I. is supported by a Stan Perron Charitable Foundation People Fellowship. S.P.A.-R. received funding from the Branchi family. A.B. is supported by the NIH (R21 AI176305-01A1, R01AI099108-11A1).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee/IRB of Ramsey Health Care HREC WA-SA gave ethical approval for this work (reference number 1908). Informed consent was obtained from the parents or caregivers of all children participating in the study.

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The taxonomy table and all de-identified datasets used for analysis are available as supplemental material and in the accompanying GitHub repository: https://github.com/jacapmar/MicrobiomeAERIAL. Due to ethical considerations regarding participant confidentiality, raw sequencing files cannot be made publicly available, however the supplemental de-identified datasets are sufficient for reproducing all reported findings. The R code is also available in the GitHub repository.