Different Phenotypes of Pediatric Asthma Show Distinct Bacterial Functional Profiles and Network Relationships

Pediatric asthma is the most common chronic childhood disease in the US and a major public health concern. It is considered to comprise multiple clinical variants or phenotypes with different etiologies and pathophysiologies. Former research has shown that airway bacteriomes vary in composition and structure across pediatric asthma phenotypes, but their functional diversity and bacterial interactions have hardly been investigated. A previous study of 163 children from Washington DC identified three statistically different asthma phenotypes, each with a unique nasopharyngeal bacterial composition and diversity. Here, I reanalyze 16S rRNA high-throughput sequences from the same cohort to characterize their bacterial metabolism and interactions. I detect 61 to 102 metabolic pathways (PICRUSt2; q ≤ 0.05) differentially expressed across the three asthma phenotypes. Most of those pathways are related to biosynthesis and degradation processes and statistically (p ≤ 0.0012) separated the three clinical groups. Co-occurrence networks also differ in connectivity across phenotypes, suggesting unique bacterial interactions in each group. Five to eight keystone taxa are detected across phenotypes. Insights from this and previous studies, hence, confirm the airway bacteriome heterogeneity across pediatric asthma, increasing our understanding of its etiology and pathophysiology, and provide new taxonomic and functional biomarkers of disease for targeted interventions and therapies.