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<p>Pregnancy-induced hypertension (PIH) is a major cause of maternal and perinatal morbidity. However, 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. This was characterized by a persistent enrichment of <i>Bacteroides stercoris</i> and <i>Bacteroides eggerthii</i>. Microbial pathways including amino acid biosynthesis and 2-oxocarboxylic acid metabolism were perturbed before diagnosis, with <i>Bacteroides stercoris</i> as a key contributor. Co-occurrence networks revealed <i>Bacteroides-</i>driven ecological restructuring. Plasma metabolomics identified stage-specific host disturbances. In early pregnancy, glycolytic intermediates were elevated, whereas in mid-pregnancy, bile acid and arachidonic acid metabolism were dysregulated. Notably, these changes included increased cholic acid and decreased pro-resolving mediators such as 15(R)-Lipoxin A4 (15-R-LxA4). These metabolic shifts correlated with microbial features, suggesting microbiota-linked vascular and inflammatory regulation prior to PIH diagnosis. In conclusion, impaired microbiome remodeling and associated metabolic disturbances precede the onset of PIH and may contribute to its development, although causal relationships require further investigation.</p> Graphical Abstract <p></p>

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Pregnancy-induced hypertension are preceded by prenatal perturbations of the gut microbiome and metabolome

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月30日

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  • Huiyuan Pang,
  • Bo Peng,
  • Xin Yan,
  • Jia Wang,
  • Yixuan Lu,
  • Xianxian Yuan,
  • Yujie Zhang,
  • Lirui Zhang,
  • Junhua Huang,
  • Ya Zhang,
  • Ruihua Yang,
  • Xu Ma,
  • Xiaoxin Wang,
  • Chenchen Fan,
  • Li Zhang,
  • Wei Song,
  • Yumei Cheng,
  • Shengnan Liang,
  • Yuanyuan Wang,
  • Wei Zheng,
  • Guanghui Li

摘要

Pregnancy-induced hypertension (PIH) is a major cause of maternal and perinatal morbidity. However, 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. This was characterized by a 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. In early pregnancy, glycolytic intermediates were elevated, whereas in mid-pregnancy, bile acid and arachidonic acid metabolism were dysregulated. Notably, these changes included increased cholic acid and decreased pro-resolving mediators such as 15(R)-Lipoxin A4 (15-R-LxA4). These metabolic shifts correlated with microbial features, suggesting microbiota-linked vascular and inflammatory regulation prior to PIH diagnosis. In conclusion, impaired microbiome remodeling and associated metabolic disturbances precede the onset of PIH and may contribute to its development, although causal relationships require further investigation.

Graphical Abstract