Exploratory integrative analysis of infant gut microbiome and metabolome suggests diet- and microbiome-derived metabolites associated with childhood asthma

Abstract

Early-life gut microbiome composition has been linked to childhood asthma risk, but the metabolic pathways underlying this association remain unclear. To integrate infant gut microbiome and metabolome data to identify pathways associated with asthma risk. Participants were from the INSPIRE birth cohort with early infancy 16S rRNA microbiome data (n=402), urinary metabolomics (n=199), and stool metabolomics (n=58). Overlapping datasets included 89 (urine) and 58 (stool) infants. Current asthma at age 6 was assessed by validated questionnaires. Nested sparse partial least squares discriminant analysis prioritized metabolites and amplicon sequence variants (ASVs) feature selection, followed by Spearman rank correlations to evaluate metabolite-microbiome associations with Bonferroni correction. Several significant correlations were identified in associations between the stool microbiome and metabolites, primarily involving lipid-related metabolites and microbiome taxa such as Staphylococcus sp. (unclassified), Enterobacteriaceae sp. (unclassified), Veillonella sp. (unclassified), Thomasclavelia ramosa, Bacteroides sp.(unclassified), and Clostridium innocuum group. The correlations between stool microbiome and urine metabolites were weak. Many associated metabolites are likely diet-derived, with microbiome co-metabolising. Exploratory microbiome-metabolite correlations suggest diet-related metabolites may link the infant gut environment to later asthma risk. Exploratory correlations between prioritized infant gut taxa and metabolites generate hypotheses for future studies of early-life asthma development.