Preeclampsia and environmental epigenomics: the emerging role of air pollution, gut microbiome, and maternal exposures in disease programming

TL;DR

This review explores how environmental factors like air pollution and gut microbiome may influence preeclampsia through epigenetic changes during pregnancy.

Contribution

The paper highlights the emerging role of environmental epigenomics in preeclampsia and identifies gaps in causal evidence.

Findings

Observational studies link air pollution and gut microbiome to epigenetic changes associated with preeclampsia.

MicroRNAs and DNA methylation patterns show associations with preeclampsia and environmental exposure.

Animal studies suggest microbiota-derived metabolites may affect placental development via epigenetic pathways.

Abstract

Preeclampsia (PE) remains a major contributor of maternal and fetal morbidity and mortality worldwide, affecting 2%–8% of pregnancies. While genetic predisposition, placental dysfunction, and angiogenic imbalance remain central to PE pathophysiology, emerging observational evidence suggests potential associations between environmental factors, epigenetic modifications, and PE development. This review consolidates available research linking environmental exposures, particularly air pollution, maternal gut microbiome composition, and dietary habits, with changes in epigenetic markers during pregnancy that may influence PE susceptibility. We synthesize findings from epidemiological studies, mechanistic research, and biomarker studies across this research area. However, definitive causal evidence linking specific environmental exposures to PE through epigenetic mechanisms remains limited. The majority of existing studies employ observational designs or focus on biological mechanisms; well-designed prospective cohorts incorporating direct environmental measurements and randomized intervention trials are lacking. Circulating biomarkers, including microRNAs and DNA methylation patterns, show associations with both PE status and prior environmental exposure, providing biological support for the concept that environmental factors may influence PE development. The maternal gut microbiome demonstrates dysbiosis in PE patients, and mechanistic studies in animal models suggest that microbiota-derived metabolites may influence placental development through epigenetic pathways; however, clinical evidence in humans remains preliminary. Integration of environmental exposure assessment with multi-omics profiling in large prospective studies is necessary to establish whether environmental factors causally contribute to PE pathogenesis. Future research combining detailed environmental characterization, longitudinal epigenomic profiling, and rigorous causal inference methods will be essential to translate these mechanistic insights into prevention and therapeutic strategies.

Graphical Abstract

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