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. 2025 Feb;155(2):436-450.
doi: 10.1016/j.jaci.2024.11.008. Epub 2024 Nov 14.

Early-life upper airway microbiota are associated with decreased lower respiratory tract infections

Susan Zelasko  1 , Mary Hannah Swaney  2 , Shelby Sandstrom  3 , Kristine E Lee  4 , Jonah Dixon  5 , Colleen Riley  5 , Lauren Watson  5 , Jared J Godfrey  5 , Naomi Ledrowski  5 , Federico Rey  6 , Nasia Safdar  7 , Christine M Seroogy  8 , James E Gern  9 , Lindsay Kalan  10 , Cameron Currie  11
Affiliations
Free article

Early-life upper airway microbiota are associated with decreased lower respiratory tract infections

Susan Zelasko et al. J Allergy Clin Immunol. 2025 Feb.
Free article

Abstract

Background: Microbial interactions mediating colonization resistance play key roles within the human microbiome, shaping susceptibility to infection from birth. The role of the nasal and oral microbiome in the context of early life respiratory infections and subsequent allergic disease risk remains understudied.

Objectives: Our aim was to gain insight into microbiome-mediated defenses and respiratory pathogen colonization dynamics within the upper respiratory tract during infancy.

Methods: We performed shotgun metagenomic sequencing of nasal (n = 229) and oral (n = 210) microbiomes from our Wisconsin Infant Study Cohort at age 24 months and examined the influence of participant demographics and exposure history on microbiome composition. Detection of viral and bacterial respiratory pathogens by RT-PCR and culture-based studies with antibiotic susceptibility testing, respectively, to assess pathogen carriage was performed. Functional bioassays were used to evaluate pathogen inhibition by respiratory tract commensals.

Results: Participants with early-life lower respiratory tract infection were more likely to be formula fed, attend day care, and experience wheezing. Composition of the nasal, but not oral, microbiome associated with prior lower respiratory tract infection, namely lower alpha diversity, depletion of Prevotella, and enrichment of Moraxella catarrhalis including drug-resistant strains. Prevotella originating from healthy microbiomes had higher biosynthetic gene cluster abundance and exhibited contact-independent inhibition of M catarrhalis.

Conclusions: These results suggest interbacterial competition affects nasal pathogen colonization. This work advances understanding of protective host-microbe interactions occurring in airway microbiomes that alter infection susceptibility in early life.

Keywords: Moraxella catarrhalis; Nasal microbiome; Prevotella; asthma; children; oral microbiome; pediatric; pneumonia; respiratory tract infection; wheezing.

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Conflict of interest statement

Disclosure statement Supported by grants from the National Institutes of Health: U19AI142720 (C.R.C., L.R.K.), National Institute of Allergy and Infectious Diseases (NIAID) F30AI169759 (S.Z.), National Center for Advancing Translational Sciences (NCATS) TL1TR002375 (S.Z.), NIAID T32AI055397 (M.H.S.), National Institute of Arthritis and Musculoskeletal and Skin Diseases F31AR079846 (M.H.S.), NIAID U19AI104317 (J.E.G., C.M.S.), NCATS UL1TR000427 (J.E.G, C.M.S), and NIAID U01AI125053 (N.S.). Also supported by the University of Wisconsin School of Medicine and Public Health Wisconsin Partnership Program (C.M.S., J.E.G.), and the Jarislowsky Foundation (C.R.C.). The funders had no role in study design, data collection and interpretation, or the decision to submit the report for publication. Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest. Data availability: Raw metagenomic sequences generated for this work are deposited in the Short Read Archive under BioProject PRJNA1078287. Adult raw metagenome reads were downloaded from the iHMP data portal (portal.hmpdacc.org/). All scripts and derived data necessary to replicate this work are available (github.com/szelasko1/AirwayMicrobiome_paper), as are the data for BGC analysis (github.com/reedstubbendieck/adt_bgcs).

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