Obstetrics

Preeclampsia

Confidence interval

Biology

Gene

Genotype

Mendelian randomization

Odds ratio

Eclampsia

Internal medicine

Pregnancy

Genetic variants

Genetics

Medicine

BMC Medicine

Background Several recent observational studies have reported that gut microbiota composition is associated with preeclampsia. However, the causal effect of gut microbiota on preeclampsia-eclampsia is unknown. Methods A two-sample Mendelian randomization study was performed using the summary statistics of gut microbiota from the largest available genome-wide association study meta-analysis ( n =13,266) conducted by the MiBioGen consortium. The summary statistics of preeclampsia-eclampsia were obtained from the FinnGen consortium R7 release data (5731 cases and 160,670 controls). Inverse variance weighted, maximum likelihood, MR-Egger, weighted median, weighted model, MR-PRESSO, and cML-MA were used to examine the causal association between gut microbiota and preeclampsia-eclampsia. Reverse Mendelian randomization analysis was performed on the bacteria that were found to be causally associated with preeclampsia-eclampsia in forward Mendelian randomization analysis. Cochran’s Q statistics were used to quantify the heterogeneity of instrumental variables. Results Inverse variance weighted estimates suggested that Bifidobacterium had a protective effect on preeclampsia-eclampsia (odds ratio = 0.76, 95% confidence interval: 0.64–0.89, P = 8.03 × 10 −4 ). In addition, Collinsella (odds ratio = 0.77, 95% confidence interval: 0.60–0.98, P = 0.03), Enterorhabdus (odds ratio = 0.76, 95% confidence interval: 0.62–0.93, P = 8.76 × 10 −3 ), Eubacterium (ventriosum group) (odds ratio = 0.76, 95% confidence interval: 0.63–0.91, P = 2.43 × 10 −3 ), Lachnospiraceae (NK4A136 group) (odds ratio = 0.77, 95% confidence interval: 0.65–0.92, P = 3.77 × 10 −3 ), and Tyzzerella 3 (odds ratio = 0.85, 95% confidence interval: 0.74–0.97, P = 0.01) presented a suggestive association with preeclampsia-eclampsia. According to the results of reverse MR analysis, no significant causal effect of preeclampsia-eclampsia was found on gut microbiota. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. Conclusions This two-sample Mendelian randomization study found that Bifidobacterium was causally associated with preeclampsia-eclampsia. Further randomized controlled trials are needed to clarify the protective effect of probiotics on preeclampsia-eclampsia and their specific protective mechanisms.

Association between gut microbiota and preeclampsia-eclampsia: a two-sample Mendelian randomization study