Phenotype-specific signatures of systems-level gut microbiome associated with childhood airway allergies

Background: Perturbation of gut symbiosis has been linked to childhood allergic diseases. However, the underlying host–microbe interaction connected with specific phenotypes is poorly understood. Methods: To address this, integrative analyses of stool metagenomic and metabolomic profiles associated with IgE reactions in 56 children with mite-sensitized airway allergies (25 with rhinitis and 31 with asthma) and 28 nonallergic healthy controls were conducted. Results: We noted a decrease in the number and abundance of gut microbiome-encoded carbohydrate-active enzyme (CAZyme) genes, accompanied with a reduction in species richness, in the asthmatic gut microflora but not in that from allergic rhinitis. Such loss of CAZymes was consistent with the observation that a CAZyme-linked decrease in fecal butyrate was found in asthmatics and negatively correlated with mite-specific IgE responses. Different from the CAZymes, we demonstrated an increase in α diversity at the virulome levels in asthmatic gut microbiota and identified phenotype-specific variations of gut virulome. Moreover, use of fecal metagenomic and metabolomic signatures resulted in distinct effects on differentiating rhinitis and asthma from nonallergic healthy controls. Conclusion: Overall, our integrative analyses reveal several signatures of systems-level gut microbiome in robust associations with fecal metabolites and disease phenotypes, which may be of etiological and diagnostic implications in childhood airway allergies.