Association of the Gut Microbiome and Metabolome with Wheeze Frequency in Childhood Asthma

Abstract

While the gut microbiome has an established role in asthma development, less is known about its contribution to morbidity in children with asthma. In this ancillary study of the Vitamin D Antenatal Asthma Reduction Trial (VDAART), we analyzed the gut microbiome and metabolome of wheeze frequency in children with asthma. Microbiome profiling by 16S rRNA gene sequencing and metabolomic profiling by mass spectrometry were performed on fecal samples collected from 3 year-olds with parent-reported doctor-diagnosed asthma. We tabulated the proportion of quarterly questionnaires in which parents/guardians reported wheeze between months 39 and 63 of life (“wheeze proportion”). Associations of bacterial taxa with wheeze proportion were tested in negative binomial regression models including potential confounders and associations of metabolites with wheeze proportion were tested in correlation, linear regression and pathway analyses. Microbe-metabolite and microbial correlation networks were constructed. In 111 children with asthma, several bacterial taxa were associated with wheeze proportion. Among those with higher wheeze proportion, Veillonella spp. were enriched (log2FoldChanges: 3.1 for V dispar (FDR = 0.01); 3.2 for V parvula (FDR = 0.01); 3.1 for unidentified Veillonella spp. (FDR = 0.02)) and Bifidobacterium longum was depleted (log2FoldChange -2.1, FDR = 0.01). Histidine pathway metabolites were enriched in those with higher wheeze proportion (p < 0.05 using two different pathway analysis methods). V dispar and V uniformis correlated with each other and with numerous metabolites. Gut microbiome features are associated with wheeze frequency in children with asthma, suggesting an impact of the gut microbiome on morbidity in childhood asthma.