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

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. 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. 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. 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.

Li P ，Wang H ，Guo L ，Gou X ，Chen G ，Lin D ，Fan D ，Guo X ，Liu Z ... -  《BMC Medicine》

Association between gut microbiota and primary ovarian insufficiency: a bidirectional two-sample Mendelian randomization study.

Recent studies have indicated a potential correlation between intestinal bacteria and primary ovarian insufficiency (POI). However, the causal relationship between the gut microbiota (GM) and POI remains unclear. A bidirectional two-sample Mendelian randomization (MR) study was conducted to investigate the relationship between the GM and POI. Data on the GM were based on the MiBioGen consortium's summary statistics from the most comprehensive genome-wide association study meta-analysis to date (n=13,266), and POI data were obtained from the R8 release of the FinnGen consortium, containing a total of 424 cases and 181,796 controls. A variety of analytical methods, including inverse variance weighting, maximum likelihood, MR-Egger, weighted median, and constrained maximum likelihood and model averaging and Bayesian information criterion, were utilized to explore the connection between the GM and POI. The Cochran's Q statistics were used to evaluate the heterogeneity of instrumental variables. The MR-Egger and MR-pleiotropy residual sum and outlier (PRESSO) methods were used to identify the horizontal pleiotropy of instrumental variables. The MR Steiger test was used to evaluate the strength of causal relationships. A reverse MR study was performed to investigate the causal relationship between POI and the targeted GMs which were indicated to have a causal relationship with POI in the forward MR evaluation. The inverse variance weighted analysis indicated that Eubacterium (hallii group) (odds ratio [OR]=0.49, 95% confidence interval [CI]: 0.26-0.9, P=0.022) and Eubacterium (ventriosum group) (OR=0.51, 95% CI: 0.27-0.97, P=0.04) had protective effects on POI, and Intestinibacter (OR=1.82, 95% CI: 1.04-3.2, P=0.037) and Terrisporobacter (OR=2.47, 95% CI: 1.14-5.36, P=0.022) had detrimental effects on POI. Results of the reverse MR analysis indicated that POI had no significant influence on the four GMs. No significant heterogeneity or horizontal pleiotropy was observed in the performance of the instrumental variables. This bidirectional two-sample MR study revealed a causal link between Eubacterium (hallii group), Eubacterium (ventriosum group), Intestinibacter, and Terrisporobacter and POI. Additional clinical trials are needed to gain a clearer understanding of the beneficial or detrimental effects of the GMs on POI and their mechanisms of action.

Wang J ，Luo R ，Zhao X ，Xia D ，Liu Y ，Shen T ，Liang Y ... -  《Frontiers in Endocrinology》

Association between gut microbiota and sensorineural hearing loss: a Mendelian randomization study.

Yin Q ，Shi G ，Zhu L 《Frontiers in Microbiology》

The Causal Relationship between the Morning Chronotype and the Gut Microbiota: A Bidirectional Two-Sample Mendelian Randomization Study.

Chen M ，Wang Z ，Tan DS ，Wang X ，Ye Z ，Xie Z ，Zhang D ，Wu D ，Zhao Y ，Qu Y ，Jiang Y ... -  《Nutrients》

Causal associations between Helicobacter pylori infection and pregnancy and neonatal outcomes: a two-sample Mendelian randomization study.

Observational studies have reported that Helicobacter pylori (H. pylori) infection is associated with a series of pregnancy and neonatal outcomes. However, the results have been inconsistent, and the causal effect is unknown. A two-sample Mendelian randomization (MR) study was performed using summary-level statistics for anti-H. pylori IgG levels from the Avon Longitudinal Study of Parents and Children Cohort. Outcome data for pregnancy (miscarriage, preeclampsia-eclampsia, gestational diabetes mellitus, placental abruption, premature rupture of membranes, postpartum hemorrhage) and neonates (birthweight, gestational age, and preterm birth) were sourced from genome-wide association meta-analysis as well as the FinnGen and Early Growth Genetics Consortium. Causal estimates were calculated by five methods including inverse variance weighted (IVW). The heterogeneity of instrumental variables was quantified by Cochran's Q test, while sensitivity analyses were performed via MR-Egger, MR-PRESSO, and leave-one-out tests. IVW estimates suggested that genetically predicted anti-H. pylori IgG levels were significantly associated with increased risks of preeclampsia-eclampsia (odds ratio [OR] = 1.12, 95% confidence interval [CI] 1.01-1.24, P = 0.026) and premature rupture of membranes (OR = 1.17, 95% CI 1.05-1.30, P = 0.004). Similar results were obtained for preeclampsia-eclampsia from the MR-Egger method (OR = 1.32, 95% CI 1.06-1.64, P = 0.027) and for premature rupture of membranes from the weighted median method (OR = 1.22, 95% CI 1.06-1.41, P = 0.006). No significant causal effects were found for other outcomes. There was no obvious heterogeneity and horizontal pleiotropy across the MR analysis. Our two-sample MR study demonstrated a causal relationship of H. pylori infection with preeclampsia-eclampsia and premature rupture of membranes. The findings confirm the epidemiological evidence on the adverse impact of H. pylori in pregnancy. Further studies are needed to elucidate the pathophysiological mechanisms and assess the effectiveness of pre-pregnancy screening and preventive eradication.

Huang J ，Liu Y ，Xu D ，Chen M ，Xie Q ，Chen J ，Xia L ，Yu L ，Wu Q ，Li Z ，Wang J ，Tian L ... -  《Frontiers in Cellular and Infection Microbiology》