Previous research has confirmed the significant association between gut microbiota (GM) and male infertility (MI), but the causality between them remains unclear. This study aims to investigate the causal relationship between GM and MI using Mendelian randomization (MR) and provide supplementary information for the optimization of future randomized controlled trials (RCTs). Instrumental variables for 211 GM taxa were obtained from genome-wide association studies (GWAS), and inverse variance weighted (IVW) method was used as the main analysis method for two-sample MR analysis to assess the impact of GM on the risk of MI. Four methods were used to test for horizontal pleiotropy and heterogeneity of MR results to ensure the reliability of the MR findings. A total of 50 single-nucleotide polymorphisms (SNPs) closely related to GM were included, and ultimately identified 1 family and 4 general are causally associated with MI. Among them, Anaerotruncus (OR = 1.96, 95% CI 1.31–3.40, P = 0.016) is significantly associated with increased MI risk. Furthermore, we used four MR methods to evaluate the causality, and the results supported these findings. The leave-one-out analysis showed stable results with no instrumental variables exerting strong influence on the results. The causal direction indicated a positive effect, and the effects of heterogeneity and horizontal pleiotropy on the estimation of causal effect were minimized. We confirmed a causal relationship between GM taxa and MI, providing new insights into the mechanisms underlying GM-mediated MI.

先前的研究已证实肠道微生物群（GM）与男性不育症（MI）之间存在显着关联，但它们之间的因果关系仍不清楚。本研究旨在利用孟德尔随机化（MR）研究GM与MI之间的因果关系，并为未来随机对照试验（RCT）的优化提供补充信息。通过全基因组关联研究（GWAS）获得211个转基因类群的工具变量，并以逆方差加权（IVW）法为主要分析方法进行双样本MR分析，评估转基因对心肌梗死风险的影响。采用四种方法检验MR结果的水平多效性和异质性，以确保MR结果的可靠性。共纳入50个与GM密切相关的单核苷酸多态性（SNP），最终鉴定出1个家族和4个一般与MI有因果关系。其中，Anaerotruncus (OR = 1.96, 95% CI 1.31–3.40, P  = 0.016) 与 MI 风险增加显着相关。此外，我们使用四种 MR 方法来评估因果关系，结果支持了这些发现。留一分析显示结果稳定，没有工具变量对结果产生强烈影响。因果方向表明正效应，异质性和水平多效性对因果效应估计的影响被最小化。我们证实了转基因分类群与 MI 之间的因果关系，为转基因介导的 MI 的潜在机制提供了新的见解。