Maternal antibiotic exposure enhances neonatal ILC2 responses and aggravates allergic airway inflammation in adults
The maternal microbiota plays an important role in shaping and priming infant immunity, although the cellular and molecular mechanisms underlying these effects remain obscure. Here we report that prenatal antibiotic exposure caused significant elevation of group 2 innate lymphoid cells (ILC2s) in neonatal lungs, in both cell numbers and functionality. Downregulation of type 1 interferon signaling in ILC2s caused by diminished production of microbiota-derived metabolite butyrate represents the underlying mechanism. Mice lacking butyrate receptor GPR41 (GPR41-/-) or type 1 interferon receptor (Ifnar1-/-) recapitulated the phenotype of neonatal ILC2s upon maternal antibiotic exposure. Furthermore, prenatal antibiotic exposure induced persistent epigenetic changes in ILC2s and had a long-lasting deteriorative effect on allergic airway inflammation in adulthood. Prenatal supplementation with butyrate ameliorated airway inflammation in adult offspring born to antibiotic-exposed dams. These observations demonstrate an essential role for the maternal microbiota in the control of type 2 innate immunity at the neonatal stage, which provides a therapeutic window for treating asthma in early life. Overall design: A total of 1,000 lung ILC2s(prenatal antibiotic exposure group and control group) were sorted and lysed in 5 µL lysis buffer  for RNA-sequencing