Longitudinal Changes in Early Nasal Microbiota and the Risk of Childhood Asthma

Abstract

To explore the association between longitudinal changes in early nasal microbiota and the risk of developing asthma.In the study, researchers included 704 children (aged 0 to 7 years old) born in the Hospital District of Southwest Finland between January 2008 and April 2010.This was a prospective, population-based birth cohort study. Children with a qualified baseline nasal microbiota sample at 2 months old and at least 1 follow-up sample were included in the analysis. Samples were collected by using nasal and nasopharyngeal swabs. The nasal microbiota were tested by using 16S ribosomal RNA gene sequencing. An unsupervised machine learning approach was used to identify mutually exclusive, longitudinal nasal microbiota profiles. Changes in profiles between the ages of 2 to 13 months and 2 to 24 months were examined. The profile with persistent Moraxella dominance was used as the reference group because this was the largest group, a finding also supported by the literature. The primary outcome was the risk of physician-diagnosed asthma at the ages of 6.5 to 7.5 years old. The secondary outcome was the number of acute respiratory infections (ARIs) during 13 to 24 months of age. The association of the microbiota longitudinal profiles with the risk of developing asthma and rate of ARIs was measured by using multivariable logistic regression and negative binomial models.Of the 704 children in the analytic cohort, 57 (8%) developed asthma. Across all samples, the nasal airway microbiota was dominated by Moraxella, which generally increased with age. During age 2 to 13 months, 4 distinct longitudinal nasal microbiota profiles were identified: (1) persistent Moraxelladominance profile (reference group), (2) Streptococcus to Moraxella transition profile, (3) persistent Dolosigranulum and Corynebacteriaceae dominance profile, and (4) persistent Moraxella sparsity profile. During 2 to 24 months of age, an additional distinct longitudinal nasal microbiota profiles was identified: (5) a mixed longitudinal pattern profile. Overall, children with a persistent Moraxella sparsity profile were at a significantly higher risk of developing asthma (adjusted odds ratio: 2.74; 95% confidence interval: 1.20 to 6.27 for those in this profile at 2 to 13 months of age, which persisted in the 2 to 24 month profile) and had significantly higher incidence rates of ARIs (incidence rate ratio: 1.16; 95% confidence interval: 1.01 to 1.32, from 13 to 24 months of age).In this study, researchers found that, compared with the reference group (Moraxella dominant profile), children with an altered longitudinal nasal microbiota pattern (Moraxella sparsity profile) during early childhood had a higher risk of developing asthma and ARIs.This is the first study to reveal an association between longitudinal changes in early airway microbiota and later development of childhood asthma. Further efforts to develop primary prevention strategies aimed at modifying the microbiota may help to lower the incidence of childhood asthma and ARIs.