The gut-placenta axis in preeclampsia: unraveling the regulatory network and clinical prospects in pathogenesis

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder that develops after 20 weeks of gestation, characterized by hypertension and proteinuria or multi-organ dysfunction. representing a leading cause of maternal and perinatal morbidity and mortality worldwide. The pathogenesis of PE is complex and remains incompletely understood, involving shallow placentation, endothelial dysfunction, immune imbalance, and systemic inflammation;however, the initiating triggers remain are unclear. Recent research has highlighted the gut microbiota-often termed the "second genome" -for its critical role in metabolic and immune homeostasis. Dynamic alterations in maternal gut microbial composition during pregnancy are closely associated with maternal and fetal health. Concurrently, placental exosomes, have emerged as key mediators of intercellular communication. These membrane-bound extracellular vesicles, released by placental cells, are capable of delivering microRNAs, proteins, and lipids into the maternal circulation to exert systemic effects. The emerging concept of a "gut microbiota-placental -exosome axis" suggests a pivotal role in PE progression. This review explores the bidirectional interactions between gut microbiota and placental exosomes, their regulatory impact on maternal-fetal immune crosstalk and endothelial function, and their contribution to PE pathophysiology. We also identify current research gaps and propose future directions, offering a theoretical basis for early biomarkers and targeted therapies for PE.