Genetically predicted the causal relationship between gut microbiota and infertility: bidirectional Mendelian randomization analysis in the framework of predictive, preventive, and personalized medicine

ObjectiveSeveral studies have reported the association between gut microbiota and infertility; however, the causal association between them remains unclear. This study aimed to explore the causal relationship between gut microbiota and infertility and evaluate how specific gut microbiota can support early monitoring and prevention of infertility in the context of predictive, preventive, and personalized medicine (PPPM/3PM).MethodsThe gut microbiota GWAS data included 18,340 individuals. Female infertility (6481 cases and 68,969 controls) and male infertility data (680 cases and 72,799 controls) were obtained from the FinnGen consortium. The inverse variance weighting (IVW), MR-Egger, weighted median (WM), Cochran Q tests, MR-PRESSO, and leave-one-out were used as a supplement to Mendelian randomization (MR) results and sensitivity analysis.ResultsThe results of MR analysis indicated a significant causal association between Eubacterium oxidoreducens (OR = 2.048, P = 0.008), Lactococcus (OR = 1.445, P = 0.042), Eubacterium ventriosum (OR = 0.436, P = 0.018), Eubacterium rectale (OR = 0.306, P = 0.002), and Ruminococcaceae NK4A214 (OR = 0.537, P = 0.045) and male infertility. Genetically predicted Eubacterium ventriosum (OR = 0.809, P = 0.018), Holdemania (OR = 0.836, P = 0.037), Lactococcus (OR = 0.867, P = 0.020), Ruminococcaceae NK4A214 (OR = 0.830, P < 0.050), Ruminococcus torques (OR = 0.739, P = 0.022), and Faecalibacterium (OR = 1.311, P = 0.007) were associated with female infertility. Sensitivity analysis did not detect heterogeneity and pleiotropy (P > 0.05).ConclusionsOur results provided evidence for the causal relationship between some gut microbiota and male and female infertility. These findings might be valuable in providing personalized treatment options for preventing infertility and improving reproductive function by monitoring and regulating the gut microbiota of infertility patients in the context of PPPM. Moreover, detecting the abundance of microbiota in feces can support preventive and personalized strategies, which may benefit more infertility patients.