Assessing the involvement of the placental microbiome and virome in preeclampsia using a novel method for pathogen detection

Preeclampsia is one of the most dangerous complications of pregnancy and the leading cause of ‎maternal and perinatal morbidity and mortality. The cause of preeclampsia is unknown, though the ‎placenta is believed to have a central role in its pathogenesis. An association between maternal ‎infection and preeclampsia has been demonstrated, yet involvement of the placental microbiome in ‎the etiology of preeclampsia has not been determined. In this study we examined whether ‎preeclampsia is associated with an imbalanced microorganism composition in the placenta. To this end, ‎we developed a novel method for pathogen detection based on sequencing of small non-coding RNA, ‎which increases the pathogen-to-host ratio‎, this being a major challenge in pathogen detection ‎methods. We validated the method on various infected tissues and demonstrated its efficiency in ‎detecting microorganisms in samples with extremely low bacterial/viral biomass. We then applied the ‎method to placenta specimens from preeclamptic and healthy pregnancies. Since the placenta is a ‎remarkably large and heterogeneous organ, we explored the bacterial and viral RNA at each of 15 ‎distinct locations. Bacterial RNA was detected at all locations, without significant differences between ‎the preeclampsia and control groups. However, the bacterial RNA composition differed significantly ‎between various areas of the placenta. Our results suggest that the bacterial and viral abundance in ‎the placenta may have only limited involvement in the pathogenesis of preeclampsia. The evidence of ‎a heterogenic bacterial RNA composition in the various placental locations warrants further ‎investigation of regions of the placenta in order to ‎capture the true nature of the placental ‎microbiome‎. ‎