Role of the upper airway microbiota in respiratory virus and bacterial pathobiont dynamics in the first year of life

Matthew S. Kelly (), Pixu Shi, Sifelane C. Boiditswe, Emily Qin, Andrew P. Steenhoff, Tiny Mazhani, Mohamed Z. Patel, Coleen K. Cunningham, John F. Rawls, Kathy Luinstra, Jodi Gilchrist, Julia Maciejewski, Jillian H. Hurst, Patrick C. Seed, David Bulir and Marek Smieja
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Matthew S. Kelly: Botswana-University of Pennsylvania Partnership
Pixu Shi: Duke University
Sifelane C. Boiditswe: Botswana-University of Pennsylvania Partnership
Emily Qin: Duke University
Andrew P. Steenhoff: Botswana-University of Pennsylvania Partnership
Tiny Mazhani: University of Botswana School of Medicine
Mohamed Z. Patel: University of Botswana School of Medicine
Coleen K. Cunningham: Irvine
John F. Rawls: Duke University
Kathy Luinstra: Research Institute of St. Joe’s Hamilton
Jodi Gilchrist: Research Institute of St. Joe’s Hamilton
Julia Maciejewski: Research Institute of St. Joe’s Hamilton
Jillian H. Hurst: Duke University
Patrick C. Seed: Northwestern University
David Bulir: McMaster University
Marek Smieja: Research Institute of St. Joe’s Hamilton

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: Abstract The mechanisms by which respiratory viruses predispose to secondary bacterial infections remain poorly characterized. Using 2,409 nasopharyngeal swabs from 300 infants enrolled in a prospective cohort study in Botswana, we perform a detailed analysis of factors that influence the dynamics of bacterial pathobiont colonization during infancy. We quantify the extent to which viruses increase the acquisition of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. We provide evidence of cooperative interactions between these pathobionts while identifying host characteristics and environmental exposures that influence the odds of pathobiont colonization during early life. Using 16S rRNA gene sequencing, we demonstrate that respiratory viruses result in losses of putatively beneficial Corynebacterium and Streptococcus species that are associated with a lower odds of pathobiont acquisition. These findings provide important insights into viral-bacterial relationships in the upper respiratory tract of direct relevance to respiratory infections and suggest that the bacterial microbiota is a potentially modifiable mechanism by which viruses promote bacterial respiratory infections.

Date: 2025
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DOI: 10.1038/s41467-025-60552-4

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