Nasal microbiota and symptom persistence in acute respiratory tract infections in infants

Abstract

Acute respiratory tract infections (ARI) in infancy have been implicated in the development of chronic respiratory disease, but the complex interplay between viruses, bacteria and host is not completely understood. We aimed to prospectively determine whether nasal microbiota changes occur between the onset of the first symptomatic ARI in the first year of life and 3 weeks later, and to explore possible associations with the duration of respiratory symptoms, as well as with host, environmental and viral factors. Nasal microbiota of 167 infants were determined at both time-points by 16S ribosomal RNA-encoding gene PCR amplification and subsequent pyrosequencing. Infants were clustered based on their nasal microbiota using hierarchical clustering methods at both time-points. We identified five dominant infant clusters with distinct microbiota at the onset of ARI but only three clusters after 3 weeks. In these three clusters, symptom persistence was overrepresented in the Streptococcaceae-dominated cluster and underrepresented in the cluster dominated by "Others" (p<0.001). Duration of symptoms was not associated with the type of respiratory virus. Infants with prolonged respiratory symptoms after their first ARI tend to exhibit distinct microbial compositions, indicating close microbiota-host interactions that seem to be of importance for symptom persistence and recovery.

FIGURE 1

Flow chart of the study population. ARI: acute respiratory tract infection.

FIGURE 2

Composition of the most common clusters at the a) onset of the first acute respiratory tract infection (swab A) and b) 3 weeks later (swab B) illustrated as bacterial abundances of the five most common bacterial families with the remaining grouped as “Others”. Clusters with sizes of <5% are not depicted.

FIGURE 3

Results of hierarchical clustering based on the microbial composition at the onset of the first acute respiratory tract infection (swab A) and 3 weeks later (swab B). The size of the circles and the numbers inside indicate the number of individuals assigned to each cluster. The connecting bars indicate the transition from one particular cluster to another between swabs A and B; the size of the bars corresponds to the number of transitioning individuals. The dominating bacterial families in the clusters are as follows. A1: Moraxellaceae; A2: Moraxellaceae and Streptococcaeae; A3: Streptococcaceae; A4: “Others”; A5: Pasteurellaceae; B1: Moraxellaceae; B2: “Others”; B3: Streptococcaceae. Areas in the circles of darker green on the left side of the panel indicate the proportion of infants at swab A in each cluster who were asymptomatic at swab B compared to the proportion of symptomatic infants at swab B (lighter green). Areas in the circles of darker orange on the right side of the panel indicate the proportion of asymptomatic infants at swab B compared to the proportion of symptomatic infants (lighter orange). SDI: Shannon Diversity Index, presented as the median value.