Background: Recent studies have shown that gut microbiota (GM) is related to hypertensive disorders in pregnancy (HDP). However, the causal relationship needs to be treated with caution due to confounding factors and reverse causation.
Methods: We obtained genetic variants from genome-wide association studies including GM (N = 18,340) in MiBioGen Consortium as well as HDP (7,686 cases/115,893 controls) and specific subtypes in FinnGen Consortium. Then, Inverse variance weighted, maximum likelihood, weighted median, MR-Egger, and MR.RAPS methods were applied to examine the causal association. Reverse Mendelian randomization (RMR) and multivariable MR were performed to confirm the causal direction and adjust the potential confounders, respectively. Furthermore, sensitivity analyses including Cochran's Q statistics, MR-Egger intercept, MR-PRESSO global test, and the leave-one-out analysis were conducted to detect the potential heterogeneity and horizontal pleiotropy.
Results: The present study found causalities between eight gut microbial genera and HDP. The HDP-associated gut microbial genera identified by MR analyses varied in different subtypes. Specifically, our study found causal associations of LachnospiraceaeUCG010, Olsenella, RuminococcaceaeUCG009, Ruminococcus2, Anaerotruncus, Bifidobacterium, and Intestinibacter with GH, of Eubacterium (ruminantium group), Eubacterium (ventriosum group), Methanobrevibacter, RuminococcaceaeUCG002, and Tyzzerella3 with PE, and of Dorea and RuminococcaceaeUCG010 with eclampsia, respectively.
Conclusions: This study first applied the MR approach to detect the causal relationships between GM and specific HDP subtypes. Our findings may promote the prevention and treatment of HDP targeted on GM and provide valuable insights to understand the mechanism of HDP in different subtypes from the perspective of GM.
Keywords: causal relationship; gut microbiota; hypertensive disorders in pregnancy; mendelian randomization; pre-eclampsia.