Temporal Dynamics of the Nasopharyngeal Microbiome and its Relationship with Childhood Asthma Exacerbation

Abstract

ABSTRACT Despite distinct nasopharyngeal microbiome (NPM) profiles between asthmatics and healthy subjects, little is known about the NPM dynamics and its relation to childhood asthma exacerbation (AE). We investigated NPM changes by longitudinally collecting 135 flocked nasopharyngeal swabs (FNPSs) from 33 school-age asthmatic children at six time points (2 to 4-week intervals) from September to December 2017 in Hong Kong. Subjects were categorized into AE and stable asthma (AS) groups according to whether they experienced any exacerbation during follow-up. One-off FNPSs from nine nonasthmatic children were included as controls. Microbiota profiles were analyzed using 16S rRNA gene sequencing. All 144 NPMs were classified into six microbiome profile groups (MPGs), each dominated by Moraxella, Corynebacterium 1, Dolosigranulum, Staphylococcus, Streptococcus, or Anoxybacillus. The microbial diversity and compositions of NPM in exacerbation samples were different from both baseline samples and those from healthy controls. Moraxella and Dolosigranulum-dominated NPM exhibited high temporal stability revealed by MPG transition analysis. NPM diversity decreased whereas microbial composition remained similar over time. The relative abundances of Moraxella increased while Corynebacterium 1, Anoxybacillus, and Pseudomonas decreased longitudinally. However, these temporal patterns did not differ between AE and AS groups, suggesting that short-term dynamic patterns were not sufficient to predict AE occurrence. Asthmatic NPM underwent Moraxella expansion during AE and presented a high microbiome resilience (recovery potential) after AE resolution. Microbial pathways involved in methane, ketone bodies, and vitamin B3 metabolisms were enhanced during AE and primarily contributed by Moraxella. IMPORTANCE Evidence on the dynamic changes of NPM in asthmatic patients remains limited. Here, we present that asthmatic NPMs deviating from a healthy status still showed resilience after disturbance. Our data imply from a longitudinal perspective that Moraxella increase is closely related to AE occurrence. The finding of functional dysbiosis (imbalance) during AE offers a plausible explanation for the known association between nasopharyngeal Moraxella expansion and increased AE risk. This work serves as a basis for future long-term prospective studies leveraging multiomics approaches to elucidate the temporal association between NPM and pediatric AE.

Keywords

• asthma exacerbation
• dynamics
• longitudinal sampling
• microbiome profile group
• nasopharyngeal microbiome