Longitudinal change of gut microbiota in hypertensive disorders in pregnancy: a nested case–control and Mendelian randomization study

Mounting evidence has shown that gut microbiota (GM) is related to hypertensive disorders in pregnancy (HDP), however, most studies only focused on one time point in pregnancy. In this study, we conducted a nested case–control study utilizing a follow-up cohort, resulting in the collection of 47 HDP patients and 30 healthy controls. The GM profiles were explored using 16S rRNA sequencing at three time points during pregnancy. The diversity analysis of GM showed no significant difference between HDP patients and controls, however, we found 21 differential GM during pregnancy. Trend analysis showed that there are statistical differences in the relative abundance of Thermomonas, Xanthomonas, and Phenylobacteriumat during pregnancy in the gestational hypertension group, and of Xanthomonas, Polycyclovorans, and Phenylobacterium in the control group. The correlation study found that six genera of GM are related to blood pressure. Furthermore, the MR analysis identified the causal relationship between Methanobrevibacter and pre-eclampsia (PE). This study first explored the longitudinal change of GM in HDP patients during pregnancy, found the differential GM, and detected the causal association. Our findings may promote the prevention and treatment of HDP from the perspective of GM and provide valuable insights into the pathogenesis of HDP.