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

Susan Zelasko; Mary Hannah Swaney; Shelby Sandstrom; Kristine E Lee; Jonah Dixon; Colleen Riley; Lauren Watson; Jared J Godfrey; Naomi Ledrowski; Federico Rey; Nasia Safdar; Christine M Seroogy; James E Gern; Lindsay Kalan; Cameron Currie

doi:10.1016/j.jaci.2024.11.008

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

J Allergy Clin Immunol. 2024 Nov 14:S0091-6749(24)01189-8. doi: 10.1016/j.jaci.2024.11.008. Online ahead of print.

Authors

Affiliations

¹ Department of Bacteriology, University of Wisconsin-Madison, Madison, Wis; Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, Wis. Electronic address: [email protected].
² Microbiology Doctoral Training Program, University of Wisconsin-Madison, Madison, Wis; Department of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wis.
³ Department of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wis.
⁴ Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, Wis.
⁵ Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
⁶ Department of Bacteriology, University of Wisconsin-Madison, Madison, Wis.
⁷ Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis; William S. Middleton Memorial Veterans Affairs Hospital, Madison, Wis.
⁸ Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
⁹ Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis; Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wis.
¹⁰ Department of Medical Microbiology and Immunology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wis; Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wis; M. G. DeGroote Institute for Infectious Disease Research, David Braley Centre for Antibiotic Discovery, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
¹¹ Department of Bacteriology, University of Wisconsin-Madison, Madison, Wis; M. G. DeGroote Institute for Infectious Disease Research, David Braley Centre for Antibiotic Discovery, Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada. Electronic address: [email protected].

PMID: 39547283
DOI: 10.1016/j.jaci.2024.11.008

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.