Association between gut microbiota and preeclampsia-eclampsia: a two-sample Mendelian randomization study. 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). 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), Eubacterium (ventriosum group) (odds ratio = 0.76, 95% confidence interval: 0.63-0.91, P = 2.43 × 10), Lachnospiraceae (NK4A136 group) (odds ratio = 0.77, 95% confidence interval: 0.65-0.92, P = 3.77 × 10), 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. 10.1186/s12916-022-02657-x

Effects of Insomnia on Peptic Ulcer Disease Using Mendelian Randomization. Oxidative medicine and cellular longevity OBJECTIVES:Observational studies indicate that insomnia may increase risk of peptic ulcer disease (PUD). Our purpose is to clarify the possible causal relationship between insomnia and PUD by Mendelian randomization analyses. METHODS:We carried out analyses using summary statistics data for genetic variants reported from a GWAS of insomnia ( = up to 1,331,010 individuals) and from a GWAS of PUD ( = up to 456,327 individuals). Three Mendelian randomization approaches were used to explore whether insomnia might play a causal role in PUD, and pathway and functional enrichment analyses were conducted to anticipate the underlying mechanisms. RESULTS:Conventional Mendelian randomization analysis showed clear causality between insomnia and PUD; 1 SD increased insomnia incident was related to a 19% higher risk of PUD ( = 6.69 × 10; OR, 1.19 (95% CI, 1.14-1.24)). The associations between insomnia and PUD were consistent in the other two analyses performed using the weighted median method ( = 7.75 × 10; OR, 1.16 (95% CI, 1.09-1.23)) and MR-Egger regression ( = 5.00 × 10; OR, 1.27 (95% CI, 1.07-1.50)). Moreover, no evidence indicated a reverse causality between PUD events and insomnia symptoms. Pathway and functional enrichment analyses indicated that the mechanisms of insomnia effect on PUD may be through various ways, such as the immune system and oxidative stress. CONCLUSIONS:This Mendelian randomization study suggests insomnia as a causal risk factor for PUD. The potential mechanisms included may be immune and oxidative stress. These findings indicate that improving sleep quality could have substantial health benefits. 10.1155/2021/2216314

Gut microbiota and major depressive disorder: A bidirectional Mendelian randomization. Journal of affective disorders BACKGROUND:Observational studies showed an association between gut microbiota and depression, but the causality relationship between them is unclear. We aimed to determine whether there is a bidirectional causal relationship between the composition of gut microbiota and major depressive disorders (MDD) and explore the role of gut microbiota in decreasing the risk of MDD. METHODS:Our two-sample Mendelian randomization (MR) study acquired top SNPs associated with the composition of gut microbiota (n = 18,340) and with MDDs (n = 480,359) from publicly available genome-wide association studies (GWAS). The SNPs estimates were pooled using inverse-variance weighted meta-analysis, with sensitivity analyses-weighted median, MR Egger, and MR Pleiotropy Residual Sum and Outlier (PRESSO). RESULTS:The Actinobacteria class had protective causal effects on MDD (OR 0.88, 95%CI 0.87 to 0.9). The Bifidobacterium (OR 0.89, 95%CI 0.88 to 0.91) were further found to have similar effects as the Actinobacteria class. The genus Ruminococcus1 had a protective effect on MDD (OR 0.88, 95%CI 0.76 to 0.99) while the Streptococcaceae family and its genus had an anti-protective effect on MDD (OR 1.07, 95%CI 1.01 to 1.13), but these findings were not supported by the MR-Egger analysis. Bidirectional MR showed no effect of MDD on gut microbiota composition. LIMITATIONS:The use of summary-level data, the risk of sample overlap and low statistical power are the major limiting factors. CONCLUSIONS:Our MR analysis showed a protective effect of Actinobacteria, Bifidobacterium, and Ruminococcus and a potentially anti-protective effect of Streptococcaceae on MDD pathogenesis. Further studies are needed to transform the findings into practice. 10.1016/j.jad.2022.08.012