Maternal microbiota Bifidobacterium promotes placental vascularization, nutrient transport and fetal growth in mice

Abstract The gut microbiota plays a central role in regulating host metabolism. However, while substantial progress has been made in discerning how the microbiota influences host functions post birth and beyond, little has been carried out into understanding how key members of the maternal gut microbiota can influence feto-placental growth. Here, using germ-free and specific-pathogen-free mice, we demonstrate that the bacterium Bifidobacterium breve UCC2003 modulates maternal body adaptations, placental vasculature growth and nutrient transporter capacity, with implications for fetal metabolism and growth. The effects of B. breve UCC2003 on feto-placental growth are mediated, in part, by changes in the maternal and placental metabolome (i.e. acetate and carnitine). Analysis of placental vascular bed confirmed that Bifidobacterium improves fetal capillary elongation via changes in Igf2P0, Dlk1 and Mapk14 expression. Additionally, B. breve UCC2003, acting through Slc2a1 and Fatp3-4 transporters, was shown to restore fetal glycaemia and improve fetal growth in association with changes in the fetal hepatic transcriptome. This study provides knowledge towards a novel and safe therapeutic strategy for treating pregnancy disorders via modulation of the maternal gut microbiota. SignificanceMetabolism is highly influenced by the gut microbiota, which is particularly important during gestation, when key metabolites are used for feto-placental growth. However, the contribution of the maternal gut microbiota (and its microbiota-generated metabolites) in determining fetal outcomes is largely unexplored. Here, we show that maternal gut communities and specific microbiota members are key modulators of placental phenotype with important consequences for fetal development. We have revealed novel roles for a maternal Bifidobacterium species, that include the control of placental capillary morphogenesis and nutrient transporters (glucose and lipids), which affect fetal metabolism and growth. Our work has important implications for the establishment of novel therapeutic strategies to treat pregnancy complications.