ena-STUDY-UNIVERSITY OF CALIFORNIA SAN FRANCISCO-18-12-2017-23:56:29:476-60
Neonatal gut-microbiome-derived 12,13 DiHOME impedes tolerance and predicts childhood atopy and asthma
Neonates at heightened risk of childhood atopy and asthma are characterized by inter-kingdom perturbation of their gut microbiota and metabolic dysfunction that includes fecal enrichment of the linoleic acid metabolite, 12,13 DiHOME1. Treatment of human dendritic cells (DCs) with this oxylipin decreased IL-10, altered expression of peroxisome-proliferator-activated-receptor-? (PPAR?)-regulated genes, and decreased regulatory T cell (Tregs) frequency ex vivo. Mice treated with 12,13 DiHOME and subjected to a model of airway allergic sensitization had exacerbated pulmonary inflammation and decreased lung Tregs.  Fecal metagenomic sequencing from neonates who developed atopy and/or asthma revealed a significant increase in bacterial epoxide hydrolase (EH) genes. Three of these bacterial EHs can produce 12,13 DiHOME in vitro. The abundance of fecal oxylipins and bacterial EH genes in neonatal stool can be combined with known early-life risk factors to predict neonatal risk of atopy at age two and asthma at age four.
Neonates at heightened risk of childhood atopy and asthma are characterized by inter-kingdom perturbation of their gut microbiota and metabolic dysfunction that includes fecal enrichment of the linoleic acid metabolite, 12,13 DiHOME1. Treatment of human dendritic cells (DCs) with this oxylipin decreased IL-10, altered expression of peroxisome-proliferator-activated-receptor-? (PPAR?)-regulated genes, and decreased regulatory T cell (Tregs) frequency ex vivo. Mice treated with 12,13 DiHOME and subjected to a model of airway allergic sensitization had exacerbated pulmonary inflammation and decreased lung Tregs.  Fecal metagenomic sequencing from neonates who developed atopy and/or asthma revealed a significant increase in bacterial epoxide hydrolase (EH) genes. Three of these bacterial EHs can produce 12,13 DiHOME in vitro. The abundance of fecal oxylipins and bacterial EH genes in neonatal stool can be combined with known early-life risk factors to predict neonatal risk of atopy at age two and asthma at age four.