Phenotype-specific signatures of gut microbiome, resistome, virulome, and metabolome associated with childhood airway allergies.

Perturbation of gut dysbiosis has been linked to childhood allergic diseases. However, the association of fecal microbiome and metabolite profiles with specific phenotypes is poorly understood. To address this, we performed shotgun sequencing of intestinal microbiome and untargeted metabolomics profiling of fecal samples in a cohort of children mite-sensitized airway allergies (25 with rhinitis and 31 with asthma) and 28 non-allergic healthy controls. An integrative analysis of stool metagenomic and metabolomic profiles associated with IgE reactions in childhood allergic rhinitis and asthma was conducted. We noted a decrease in the number and abundance of gut microbiome-encoded carbohydrate-active enzyme (CAZyme) genes, accompanied with a reduction of within-sample species richness (α diversity), in the asthmatic gut microbiome but not in that from allergic rhinitis. Such loss of CAZymes was consistent with the observation that decreased levels of butyrate and fumarate (a metabolic precursor of propionate) were detected in the fecal samples of asthmatics. In addition, genes related to rifamycin resistance were significantly enriched in fecal samples of cases with asthma, suggesting that altered resistome in gut microbiota may contribute to respiratory health in asthmatics. Further analysis of gut virulome identified differentially abundant virulence functions in asthmatic microbiome, such as enrichments for fibrinogen binding protein, magnesium uptake, and Ebp pili genes, and depletions for flagella-mediated motility genes. Moreover, we demonstrated an inverse correlation between the abundance of Galactobacillus timonensis and serum IgE levels of the host. Our dual-omics analyses reveal several microbial gene functions and species-level clades derived from gut dysbiosis in robust associations with fecal metabolites and disease phenotypes, which may be of etiological and diagnostic implications in childhood airway allergies.