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

## TL;DR

This paper explores how the gut microbiota and placental exosomes interact to influence the development of preeclampsia, a serious pregnancy complication.

## Contribution

It introduces the novel concept of a gut microbiota-placental exosome axis in preeclampsia pathogenesis.

## Key findings

- Gut dysbiosis leads to systemic inflammation and altered metabolite production, contributing to preeclampsia.
- Stressed placenta releases exosomes with harmful microRNAs and anti-angiogenic factors, worsening endothelial dysfunction.
- The gut-placenta axis offers a new framework for understanding and targeting preeclampsia.

## Abstract

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.

The gut-placenta axis in preeclampsia pathogenesis. This schematic illustrates the bidirectional crosstalk between maternal gut microbiota and placental exosomes in PE development. Gut dysbiosis leads to altered metabolite production (decreased SCFAs, increased LPS) and systemic inflammation. Concurrently, the stressed placenta releases exosomes containing pathogenic microRNAs and anti-angiogenic factors (sFlt-1, sEng). These two pathways converge to promote endothelial dysfunction and immune dysregulation at the maternal-fetal interface, ultimately manifesting as preeclampsia. Red arrows indicate pathogenic pathways; blue indicates protective mechanisms disrupted in PE. This framework represents a novel integration of microbiome research with placental biology.Diagram showing the gut microbiota-placenta-exosomes axis. Gut dysbiosis affects metabolites, SCFAs, and inflammation factors, leading to the formation of exosomes and P-Exos. These influence preeclampsia, affecting immunological homeostasis, endothelial function, and angiogenesis.

The gut-placenta axis in preeclampsia pathogenesis. This schematic illustrates the bidirectional crosstalk between maternal gut microbiota and placental exosomes in PE development. Gut dysbiosis leads to altered metabolite production (decreased SCFAs, increased LPS) and systemic inflammation. Concurrently, the stressed placenta releases exosomes containing pathogenic microRNAs and anti-angiogenic factors (sFlt-1, sEng). These two pathways converge to promote endothelial dysfunction and immune dysregulation at the maternal-fetal interface, ultimately manifesting as preeclampsia. Red arrows indicate pathogenic pathways; blue indicates protective mechanisms disrupted in PE. This framework represents a novel integration of microbiome research with placental biology.