Neonatal gut-microbiome-derived 12,13 DiHOME impedes tolerance and promotes childhood atopy and asthma
Neonates at risk of childhood atopy and asthma are characterized by gut microbiome perturbation and fecal enrichment of 12,13 DiHOME(1); however, the underlying mechanism and source of this metabolite remain poorly understood. Here we show that 12,13 DiHOME treatment of human dendritic cells altered peroxisome proliferator-activated receptor {gamma} regulated gene expression and decreased immune tolerance. In mice, 12,13 DiHOME treatment prior to airway challenge exacerbated pulmonary inflammation and decreased lung regulatory T cells. Neonatal fecal metagenomic sequencing revealed putative bacterial sources of 12,13 DiHOME. In our cohort, three bacterial genes and their product, 12,13 DiHOME, are associated with increased odds of childhood atopy or asthma, suggesting that early-life gut-microbiome risk factors may shape immune tolerance and identify high-risk neonates years in advance of clinical symptoms.\n\nOne Sentence SummaryEarly-life gut-microbiome risk factors may shape immune tolerance and identify neonates at high-risk of disease.