Exposure to the prenatal enriched environment alters maternal gut microbiota and promotes embryonic neurodevelopment...

The signals from the maternal environment play pivotal roles in regulating fetal neurodevelopment. Postnatal enriched environment (EE) exposure promotes neurogenesis and neurodevelopment. However, the roles of prenatal EE on fetal neurodevelopment and the underlying mechanisms remain largely unknown. This study shows that prenatal EE exposure promotes neuronal development and regulates the expression of neurodevelopmental genes in fetal mice. The prenatal EE altered the maternal microbiota and enhanced the Lactobacillus levels in the maternal mice. It also significantly elevated indole-3-propionic acid (IPA), a metabolite produced by Lactobacillus, in both the maternal serum and fetal brains. IPA promoted the proliferation and neuronal differentiation of embryonic neural progenitor cells (eNPCs) by activating the aryl hydrocarbon receptor (AHR)-Src-Erk1/2 pathway in vitro and in vivo. Administration of Lactobacillus reuteri and IPA to pregnant mice also enhanced embryonic neurogenesis and neurodevelopment. Collectively, our study has revealed the essential function and underlying mechanisms of prenatal EE in regulating fetal neurodevelopment.