Pregnancy-Induced Hypertension are Preceded by Prenatal Perturbations of the Gut Microbiome and Metabolome

Pregnancy-induced hypertension (PIH) is a major cause of maternal and perinatal morbidity, yet the longitudinal dynamics of the gut microbiome before clinical onset remain poorly characterized. This nested case-control study within a prospective pregnancy cohort included 75 women who developed PIH and 195 matched controls. Fecal samples collected at early and mid-pregnancy underwent shotgun metagenomic sequencing, integrated with nontargeted plasma metabolomics and clinical data. Compared with healthy pregnancies, women who developed PIH exhibited altered gestational microbiome progression, marked by persistent enrichment of Bacteroides stercoris and Bacteroides eggerthii. Microbial pathways including amino acid biosynthesis and 2-oxocarboxylic acid metabolism were perturbed before diagnosis, with Bacteroides stercoris as a key contributor. Co-occurrence networks revealed Bacteroides-driven ecological restructuring. Plasma metabolomics identified stage-specific host disturbances: elevated glycolytic intermediates in early pregnancy and dysregulated bile acid and arachidonic acid metabolism in mid-pregnancy, including increased cholic acid and decreased pro-resolving mediators such as 15(R)-Lipoxin A4. These metabolic shifts correlated with microbial features, suggesting microbiota-linked vascular and inflammatory regulation prior to PIH diagnosis. We conclude that impaired microbiome remodeling and related metabolic alterations precede PIH, potentially playing a role in its development, though causal confirmation requires further research.