Bidirectional Mendelian randomization to explore the causal relationships between the gut microbiota and male reproductive diseases

Krausz, C. & Riera-Escamilla, A. Genetics of male infertility. Nat. Rev. Urol. 15, 369–384 (2018).Article 
CAS 
PubMed 

Google Scholar 
Bieniek, J. M., Lapin, C. D. & Jarvi, K. A. Genetics of CFTR and male infertility. Transl. Androl. Urol. 10, 1391–1400 (2021).Article 
PubMed 
PubMed Central 

Google Scholar 
Katib, A. A., Al-Hawsawi, K., Motair, W. & Bawa, A. M. Secondary infertility and the aging male, overview. CEJU 67, 184 (2014).Article 
PubMed 
PubMed Central 

Google Scholar 
Morin-Papunen, L. & Koivunen, R. Treatment of infertility–-Part II (male infertility). Duodecim 128, 1568–1575 (2012).PubMed 

Google Scholar 
Wargo, J. A. Modulating gut microbes. Science 369, 1302–1303 (2020).Article 
ADS 
CAS 
PubMed 

Google Scholar 
Massey, W. & Brown, J. M. The gut microbial endocrine organ in type 2 diabetes. Endocrinology 162, 235 (2021).Article 

Google Scholar 
Wang, S.-Z., Yu, Y.-J. & Adeli, K. Role of gut microbiota in neuroendocrine regulation of carbohydrate and lipid metabolism via the microbiota-gut-brain-liver axis. Microorganisms 8, 527 (2020).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Ramakrishna, B. S. Role of the gut microbiota in human nutrition and metabolism. J. Gastroenterol. Hepatol. 28, 9–17 (2013).Article 
CAS 
PubMed 

Google Scholar 
Zhu, B., Wang, X. & Li, L. Human gut microbiome: The second genome of human body. Protein Cell 1, 718–725 (2010).Article 
PubMed 
PubMed Central 

Google Scholar 
Rosen, C. E. & Palm, N. W. functional classification of the gut microbiota: The key to cracking the microbiota composition code: Functional classifications of the gut microbiota reveal previously hidden contributions of indigenous gut bacteria to human health and disease. BioEssays 39, 1700032 (2017).Article 

Google Scholar 
Mahiddine, F. Y., You, I., Park, H. & Kim, M. J. Commensal Lactobacilli enhance sperm qualitative parameters in dogs. Front. Vet. Sci. 9, 888023 (2022).Article 
PubMed 
PubMed Central 

Google Scholar 
Elokil, A. A. et al. Investigation of the impact of gut microbiotas on fertility of stored sperm by types of hens. Poult. Sci. 99, 1174–1184 (2020).Article 
CAS 
PubMed 

Google Scholar 
Wang, Y. & Xie, Z. Exploring the role of gut microbiome in male reproduction. Andrology 10, 441–450 (2022).Article 
CAS 
PubMed 

Google Scholar 
Sanderson, E. et al. Mendelian randomization. Nat. Rev. Methods Primers 2, 6 (2022).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Den Hollander, W. J. et al. Helicobacter pylori colonization and obesity—A Mendelian randomization study. Sci. Rep. 7, 14467 (2017).Article 
ADS 

Google Scholar 
Grover, S., Del Greco, M. F., Stein, C. M. & Ziegler, A. Mendelian randomization. In Statistical Human Genetics Vol. 1666 (ed. Elston, R. C.) 581–628 (Springer, 2017).Chapter 

Google Scholar 
Emdin, C. A., Khera, A. V. & Kathiresan, S. Mendelian randomization. JAMA 318, 1925 (2017).Article 
PubMed 

Google Scholar 
Lin, B. D., Li, Y. & Luykx, J. Mendelian randomization concerns. JAMA Psychiatry 75, 407 (2018).Article 
PubMed 

Google Scholar 
MiBioGen Consortium Initiative. Meta-analysis of human genome-microbiome association studies: The MiBioGen consortium initiative. Microbiome 6, 101 (2018).Article 

Google Scholar 
Kurilshikov, A. et al. Large-scale association analyses identify host factors influencing human gut microbiome composition. Nat. Genet. 53, 156–165 (2021).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Fu, Z., Wang, Y. & Yan, H. Male infertility risk and gut microbiota: A Mendelian randomization study. Front. Microbiol. 14, 1228693 (2023).Article 
PubMed 
PubMed Central 

Google Scholar 
Dai, M. et al. Type 2 diabetes mellitus and the risk of abnormal spermatozoa: A Mendelian randomization study. Front. Endocrinol. 13, 1035338 (2022).Article 

Google Scholar 
Liu, R., Liu, Q., Xu, S. & Mei, R. Mood instability and low back pain: A Mendelian randomization study. Front. Neurol. 14, 1252329 (2023).Article 
PubMed 
PubMed Central 

Google Scholar 
Li, P. et al. Association between gut microbiota and preeclampsia–eclampsia: A two-sample Mendelian randomization study. BMC Med. 20, 443 (2022).Article 
PubMed 
PubMed Central 

Google Scholar 
Remmelzwaal, S. et al. Inflammation and heart failure: A two-sample Mendelian randomization study. J. Cardiovasc. Med. 23, 728–735 (2022).Article 

Google Scholar 
Papadimitriou, N. et al. Physical activity and risks of breast and colorectal cancer: A Mendelian randomisation analysis. Nat. Commun. 11, 597 (2020).Article 
ADS 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Staley, J. R. et al. PhenoScanner: A database of human genotype–phenotype associations. Bioinformatics 32, 3207–3209 (2016).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Mounier, N. & Kutalik, Z. Bias correction for inverse variance weighting Mendelian randomization. Genet. Epidemiol. 47, 314–331 (2023).Article 
CAS 
PubMed 

Google Scholar 
Slob, E. A., Groenen, P. J., Thurik, A. R. & Rietveld, C. A. A note on the use of Egger regression in Mendelian randomization studies. Int. J. Epidemiol. 46, 2094–2097 (2017).Article 
PubMed 

Google Scholar 
Bowden, J., Davey Smith, G., Haycock, P. C. & Burgess, S. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet. Epidemiol. 40, 304–314 (2016).Article 
PubMed 
PubMed Central 

Google Scholar 
Pereira, T. V., Patsopoulos, N. A., Salanti, G. & Ioannidis, J. P. A. Critical interpretation of Cochran’s Q test depends on power and prior assumptions about heterogeneity. Res. Synth. Method 1, 149–161 (2010).Article 

Google Scholar 
Ong, J. & MacGregor, S. Implementing MR-PRESSO and GCTA-GSMR for pleiotropy assessment in Mendelian randomization studies from a practitioner’s perspective. Genet. Epidemiol. 43, 609–616 (2019).Article 
PubMed 
PubMed Central 

Google Scholar 
R Core Team. R: A Language and Environment for Statistical Computing. https://www.R-project.org/ (R Foundation for Statistical Computing, 2020).Yu, X.-H., Yang, Y.-Q., Cao, R.-R., Bo, L. & Lei, S.-F. The causal role of gut microbiota in development of osteoarthritis. Osteoarthr. Cartil. 29, 1741–1750 (2021).Article 

Google Scholar 
Huang, D. et al. GWAS4D: Multidimensional analysis of context-specific regulatory variant for human complex diseases and traits. Nucleic Acids Res. 46, W114–W120 (2018).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Dang, K. et al. Transcriptomic and proteomic time-course analyses based on metascape reveal mechanisms against muscle atrophy in hibernating Spermophilus dauricus. Compar. Biochem. Physiol. A Mol. Integr. Physiol. 275, 111336 (2023).Article 
CAS 

Google Scholar 
Turner, K. A. et al. Male infertility is a women’s health issue—Research and clinical evaluation of male infertility is needed. Cells 9, 990 (2020).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Hao, Y. et al. Gut microbiota-testis axis: FMT mitigates high-fat diet-diminished male fertility via improving systemic and testicular metabolome. Microbiol. Spectr. 10, e00028 (2022).Article 
PubMed 
PubMed Central 

Google Scholar 
Zhang, T. et al. Disrupted spermatogenesis in a metabolic syndrome model: The role of vitamin A metabolism in the gut-testis axis. Gut 71, 78–87 (2022).Article 
CAS 
PubMed 

Google Scholar 
Hao, Y. et al. Gut microbiota-testis axis: FMT mitigates high-fat diet-diminished male fertility via improving systemic and testicular metabolome. Microbiol. Spectr. 10, e0002822 (2022).Article 
PubMed 

Google Scholar 
Chassaing, B., Aitken, J. D., Gewirtz, A. T. & Vijay-Kumar, M. Gut microbiota drives metabolic disease in immunologically altered mice. Adv. Immunol. 116, 93–112 (2012).Article 
CAS 
PubMed 

Google Scholar 
Nahid, M. A., Satoh, M. & Chan, E. K. MicroRNA in TLR signaling and endotoxin tolerance. Cell Mol. Immunol. 8, 388–403 (2011).Article 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Li, T. et al. A two-sample Mendelian randomization analysis investigates associations between gut microbiota and infertility. Sci. Rep. 13, 11426 (2023).Article 
PubMed 
PubMed Central 

Google Scholar 
Antonouli, S. et al. Sperm plasma membrane ion transporters and male fertility potential: A perspective under the prism of cryopreservation. Cryobiology 114, 104845 (2024).Article 
CAS 
PubMed 

Google Scholar 
Duan, Y.-G. et al. Immunodeviation towards a Th17 immune response associated with testicular damage in azoospermic men: Testicular Th17 immune response in azoospermic men. Int. J. Androl. 34, e536–e545 (2011).Article 
CAS 
PubMed 

Google Scholar 
Losdat, S., Richner, H., Blount, J. D. & Helfenstein, F. Immune activation reduces sperm quality in the great tit. PLoS ONE 6, e22221 (2011).Article 
ADS 
CAS 
PubMed 
PubMed Central 

Google Scholar 
Kohlmeier, M. & Baah, E. When Mendelian randomisation fails. BMJNPH 4, 1–3 (2021).Article 

Google Scholar 

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