Serum metabolome is associated with nasopharyngeal microbiota and disease severity among infants with bronchiolitis.

Background: Emerging evidence suggests relations of nasopharyngeal metabolome and microbiota with bronchiolitis severity. However, the influence of host systemic metabolism on disease pathobiology remains unclear. We aimed to examine metabolome profiles and their association with higher severity, defined by use of positive pressure ventilation (PPV), in infants hospitalized for bronchiolitis.

Methods: In 140 infants with bronchiolitis, metabolomic profiling was performed on serum: n=70 in the training dataset and n=70 independent samples in the test dataset. We also profiled the nasopharyngeal airway microbiota and examined its association with the serum metabolites.

Results: Serum metabolome profiles differed by bronchiolitis severity (P<0.001). In total, 20 metabolites in the training dataset were significantly associated with the risk of PPV and 18 metabolites remained significant following adjustment for confounders (FDR<0.10). Phosphatidylcholine metabolites were associated with higher risks of PPV use, while metabolites from the plasmalogen sub-pathway were associated with lower risks. The test dataset validated these findings (FDR<0.05). Streptococcus abundance was positively associated with metabolites that are associated with higher risks of PPV.

Conclusions: Serum metabolomic signatures were associated with both the nasopharyngeal microbiota and bronchiolitis severity. Our findings advance research into the complex interrelations between airway microbiome, host systemic response, and pathobiology of bronchiolitis.