Abstract
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.
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Data Availability
The gut microbiota and male infertility GWAS summary statistics are available from MiBioGen data (https://mibiogen.gcc.rug.nl/) and the FinnGen data (https://www.finngen.fi), respectively. Both of the GWAS data are publicly available.
Abbreviations
- MR:
-
Mendelian randomization
- MI:
-
Male infertility
- GM:
-
Gut microbiota
- SNPs:
-
Single-nucleotide polymorphisms
- GWAS:
-
Genome-wide association studies
- IVW:
-
Inverse variance weighted
- MR PRESSO:
-
MR pleiotropy residual sum and outlier
- IVs:
-
Instrumental variables
- RCTs:
-
Randomized controlled trials
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This work was supported by Medical Research Subject of Jiangsu Provincial Health Commission (ZDB2020020) and the National Natural Science Foundation of China, Regional Science Foundation Project (82060866).
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Conceptualization: Runpei Deng, Qingqi Zeng. Data curation: Runpei Deng, Yebao Huang, Zhaohui Tian. Formal analysis: Runpei Deng, Yebao Huang. Funding acquisition: Qingqi Zeng, Yebao Huang. Investigation:Runpei Deng, Qingqi Zeng. Methodology: Runpei Deng, Yebao Huang. Project administration: Runpei Deng, Yebao Huang, Qingqi Zeng. Resources: Runpei Deng, Yebao Huang, Zhaohui Tian. Software: Runpei Deng, Yebao Huang. Supervision: Runpei Deng. Validation: Runpei Deng, Yebao Huang, Zhaohui Tian. Visualization: Runpei Deng, Yebao Huang. Writing—original draft: Runpei Deng. Writing—review and editing: Runpei Ddeng, Yebao Huang, Zhaohui Tian, Qingqi Zeng.
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Deng, R., Huang, Y., Tian, Z. et al. Association between gut microbiota and male infertility: a two-sample Mendelian randomization study. Int Microbiol (2024). https://doi.org/10.1007/s10123-024-00512-y
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DOI: https://doi.org/10.1007/s10123-024-00512-y