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

Yujia Xi; Chenwei Zhang; Yiqian Feng; Shurui Zhao; Yukai Zhang; Guosheng Duan; Wei Wang; Jingqi Wang

doi:10.1007/s13167-023-00332-6

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

EPMA J. 2023 Jul 7;14(3):405-416. doi: 10.1007/s13167-023-00332-6. eCollection 2023 Sep.

Authors

Yujia Xi^#^{1

2}, Chenwei Zhang^#², Yiqian Feng³, Shurui Zhao^{3

4}, Yukai Zhang⁵, Guosheng Duan², Wei Wang¹, Jingqi Wang¹

Affiliations

¹ Department of Urology, The Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, 030001 Shanxi China.
² Second School of Clinical Medicine, Shanxi Medical University, Taiyuan, 030000 China.
³ First School of Clinical Medicine, Shanxi Medical University, Taiyuan, 030000 China.
⁴ Department of Obstetrics and Gynecology, The First Hospital Shanxi Medical University, Taiyuan, 030000 China.
⁵ School of Basic Medicine, Shanxi Medical University, Taiyuan, 030000 China.

^# Contributed equally.

PMID: 37605651
PMCID: PMC10439866 (available on 2024-09-01)
DOI: 10.1007/s13167-023-00332-6

Abstract

Objective: Several 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).

Methods: The 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.

Results: The 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).

Conclusions: Our 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.

Supplementary information: The online version contains supplementary material available at 10.1007/s13167-023-00332-6.

Keywords: Causal relationship; Gut microbiota; Infertility; Mendelian randomization; Predictive preventive personalized medicine (PPPM/3PM).

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