Disturbances of the placenta-brain axis in germ-free pregnant mice†

Maternal gut microbiota changes can profoundly shape on offspring health. The placenta may be vulnerable to maternal gut microbiota alterations. Placental disruptions can influence fetal brain development and underly risks for neurobehavioral disorders. Maternal gut microbiota disruptions might affect the placenta through alterations in bacterial short chain fatty acids. The hypothesis tested is that depletion of maternal gut microbiota, as may occur in pregnant women treated with antibiotics and germ-free mice, impacts bacterial short chain fatty acids in her fecal samples and in placenta and fetal brain in her conceptuses. We assessed whether transcriptomic changes would be evident in placenta and fetal brain from conceptuses derived from germ-free relative to multi-pathogen free pregnant females. Maternal germ-free status reduced the concentrations of all measured short chain fatty acids within the stool. Two-methylbutanoic acid was significantly increased in male and female placenta and fetal brain samples in conceptuses from germ-free dams. In female and male placenta, several Prl form had altered expression in conceptuses from germ-free dams. In male placenta from germ-free dams, Hsd11b2 showed increased expression. Decreased expression of Sl6a2 in female fetal brain from germ-free dams might influence uptake of catecholamines. Results reveal depletion of maternal microbiota can lead to striking effects on the placenta-fetal brain axis. Findings raise concern as to whether maternal microbiota alterations due to other intrinsic or extrinsic factors, namely antibiotic treatment, might impact placental and neural transcriptomic profiles. Underlying mechanisms remain uncertain but may relate to changes bacterial metabolites transferred from mother to conceptus.