Infant airway microbiota and topical immune perturbations in the origins of childhood asthma

Jonathan Thorsen,Martin Mortensen,Johannes Waage,Bo L Chawes,Susanne Brix,Jakob Stokholm,Søren J Sørensen,Klaus Bønnelykke,Hans Bisgaard,Morten A Rasmussen,Asker Brejnrod

doi:10.1038/s41467-019-12989-7

Abstract

Asthma is believed to arise through early life aberrant immune development in response to environmental exposures that may influence the airway microbiota. Here, we examine the airway microbiota during the first three months of life by 16S rRNA gene amplicon sequencing in the population-based Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort consisting of 700 children monitored for the development of asthma since birth. Microbial diversity and the relative abundances of Veillonella and Prevotella in the airways at age one month are associated with asthma by age 6 years, both individually and with additional taxa in a multivariable model. Higher relative abundance of these bacteria is furthermore associated with an airway immune profile dominated by reduced TNF-α and IL-1β and increased CCL2 and CCL17, which itself is an independent predictor for asthma. These findings suggest a mechanism of microbiota-immune interactions in early infancy that predisposes to childhood asthma.

Highlights

Asthma is believed to arise through early life aberrant immune development in response to environmental exposures that may influence the airway microbiota
We derive a bacterial asthma score for each child based on abundances of these specific taxa, which is associated with a specific topical immune profile characterized by reduced tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and increased Chemokine (C-C motif) ligand 2 (CCL2) and CCL17
We identified 3,582 unique operational taxonomic units (OTUs) from 574 genera, with a median richness of 70 OTUs [53–91] per sample

Summary

Introduction

Asthma is believed to arise through early life aberrant immune development in response to environmental exposures that may influence the airway microbiota. We show that the diversity and composition of the airway microbiota, and the relative abundances of Veillonella and Prevotella, at age 1 month are associated with the development of asthma by age 6 years These and other taxa together contribute to the risk of asthma in a multivariable sparse partial least squares (sPLS) model. From this model, we derive a bacterial asthma score for each child based on abundances of these specific taxa, which is associated with a specific topical immune profile characterized by reduced tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and increased Chemokine (C-C motif) ligand 2 (CCL2) and CCL17. These findings indicate that the early-life airway microbiota may predispose to the development of asthma later in childhood through dynamic interactions with the developing immune system

Methods

Results

Conclusion