Role of the Maternal Gut Microbiota in Immune Activation at the Maternal-Fetal Interface Impact on Preeclampsia

Abstract Preeclampsia is a leading cause of morbidity and mortality in pregnant women, affecting 5-8% of gestations worldwide. Several factors such as abnormalities in maternal immunity, metabolic disorders and gut dysbiosis are known to contribute to disease development. Here, we show that dysbiosis in pregnant C57BL/6J dams increased fetal resorption, impaired placental development and altered vascularization. These changes positively correlated with increased hypoxia and reduced uterine NK cell number. Moreover, intestinal dysbiosis significantly perturbated placental carbohydrate metabolism impacting NK cell IFN-γ secretion. Of note, glucose supplementation restored placental NK cell function in vitro, suggesting that the impairment was reversible and dependent on a lower glycolytic rate. In this work, maternal gut microbiota emerges as a key player in carbohydrate metabolism during pregnancy with a pivotal role in controlling placental immunity and pregnancy outcome. These results provide insights for the identification of metabolic biomarkers and propose the microbiota as a potentially amenable target for preventive intervention of preeclampsia.