Male infertility risk and gut microbiota: a Mendelian randomization study

Fu, Zhi-da; Wang, Yao; Yan, Hong-li

doi:10.3389/fmicb.2023.1228693

Cited by 6 publications

(1 citation statement)

References 64 publications

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“…The Mendelian Randomization study method is a powerful tool in epidemiological research, utilizing genetic variation as to assess the causal association between risk factors and specific diseases (12). Previous Mendelian Randomization studies (13)(14)(15) found a causal correlation between gut microbiota and male infertility. However, these studies only focused on exploring whether there is a causal relationship between specific gut microbiota and the risk of MI, without investigating the potential mediating factors and mechanisms of disease development between them.…”

Section: Introductionmentioning

confidence: 99%

Inflammatory cytokines may mediate the causal relationship between gut microbiota and male infertility: a bidirectional, mediating, multivariate Mendelian randomization study

Zou,

Xu,

et al. 2024

Front. Endocrinol.

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IntroductionStudies have shown that the gut microbiota is associated with male infertility (MI). However, their causal relationship and potential mediators need more evidence to prove. We aimed to investigate the causal relationship between the gut microbiome and MI and the potential mediating role of inflammatory cytokines from a genetic perspective through a Mendelian randomization approach.MethodsThis study used data from genome-wide association studies of gut microbes (Mibiogen, n = 18, 340), inflammatory cytokines (NFBC1966, FYPCRS, FINRISK 1997 and 2002, n=13, 365), and male infertility (Finngen, n=120, 706) to perform two-way Mendelian randomization (MR), mediated MR, and multivariate MR(MVMR) analyses. In this study, the inverse variance weighting method was used as the primary analysis method, and other methods were used as supplementary analysis methods.ResultsIn the present study, two gut microbes and two inflammatory cytokines were found to have a potential causal relationship with MI. Of the two gut microorganisms causally associated with male infertility, Anaerotruncus increased the risk of male infertility (odds ratio = 1.81, 95% confidence interval = 1.18-2.77, P = 0.0062), and Bacteroides decreased the risk of male infertility (odds ratio = 0.57, 95% confidence interval = 0.33-0.96, P = 0.0363). In addition, of the two inflammatory cytokines identified, hepatocyte growth factor(HGF) reduced the risk of male infertility (odds ratio = 0.50, 95% confidence interval = 0.35-0.71, P = 0.0001), Monocyte chemotactic protein 3 (MCP-3) increased the risk of male infertility (odds ratio = 1.28, 95% confidence interval = 1.03-1.61, P = 0.0039). Mediated MR analysis showed that HGF mediated the causal effect of Bacteroides on MI (mediated percentage 38.9%). Multivariate MR analyses suggest that HGF may be one of the pathways through which Bacteroides affects MI, with other unexplored pathways.ConclusionThe present study suggests a causal relationship between specific gut microbiota, inflammatory cytokines, and MI. In addition, HGF may mediate the relationship between Bacteroides and MI.

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Section: Introductionmentioning

confidence: 99%

Inflammatory cytokines may mediate the causal relationship between gut microbiota and male infertility: a bidirectional, mediating, multivariate Mendelian randomization study

Zou,

Xu,

et al. 2024

Front. Endocrinol.

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

Han,

Tian,

Yang

et al. 2024

Sci Rep

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Gut bacteria might play an important role in male reproductive disorders, such as male infertility and sperm abnormalities; however, their causal role is unclear. Herein, Mendelian randomization (MR)-Egger, weighted median, inverse variance weighting, Simple mode, and Weighted mode were used to test the causal relationship between gut microbes and male reproductive diseases. The MR results were validated using various metrics. The MR results were also consolidated using reverse causality speculation, conducted using two-way MR analysis and Steiger filtering. Biological function was analysed using enrichment analyses. The results suggested that eight intestinal microflorae were causally associated with male infertility. The Eubacterium oxidoreducens group was associated with an increased risk of male infertility, while the family Bacteroidaceae was negatively associated with male reproductive diseases. Eight intestinal microflorae were causally associated with abnormal spermatozoa. The family Streptococcaceae was associated with a high risk of abnormal spermatozoa, whereas the family Porphyromonadaceae was associated with a low risk of abnormal spermatozoa. No pleiotropy was observed, this study identified a high correlation between the gut flora and the likelihood of male reproductive diseases. Future research will attempt to advance microbial-focused treatments for such diseases.

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Gut microbiota and risk of ovarian diseases: a two-sample Mendelian randomization study

Liu,

Zhu,

et al. 2024

Preprint

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Background Previous studies have reported an association between gut microbial dysbiosis and ovarian diseases, however, it is not clear whether a causal association exists. Methods Two-sample Mendelian randomization (MR) analysis was performed to genetically predict the causal effects of the gut microbiota on polycystic ovary syndrome (PCOS), premature ovarian failure (POF), ovarian endometriosis, and malignant and benign ovarian neoplasms. The inverse variance weighted (IVW) method was used as the primary statistical method. A series of sensitivity analyses, including weighted median, MR-Egger, simple mode, weighted mode methods, MR pleiotropy residual sum and outlier (MR-PRESSO) and leave-one-out analysis, were also conducted to assess the robustness of the MR analysis results. Reverse MR analysis was implemented to explore whether ovarian diseases have any causal impact on the bacterial genera. Additionally, the Cochran’s Q test was used to evaluate heterogeneity among instrumental variables. Results IVW analysis revealed that several bacteria were associated with decreased risk of PCOS, POF, ovarian endometriosis, and benign and malignant ovarian neoplasm. Moreover, several bacteria were the causes of increased risks for POF, ovarian endometriosis, and benign and malignant ovarian neoplasm, respectively. Reverse MR analysis did not reveal a significant causal effect of these ovarian diseases on the gut microbiota. These findings were robust according to extensive sensitivity analyses. Conclusion Our results provide genetic evidence to support the causal relationship between specific gut microbiota taxa and ovarian diseases; thus, the gut microbiota should be considered a preventative strategy for ovarian diseases.

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Male infertility risk and gut microbiota: a Mendelian randomization study

Cited by 6 publications

References 64 publications

Inflammatory cytokines may mediate the causal relationship between gut microbiota and male infertility: a bidirectional, mediating, multivariate Mendelian randomization study

Inflammatory cytokines may mediate the causal relationship between gut microbiota and male infertility: a bidirectional, mediating, multivariate Mendelian randomization study

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

Gut microbiota and risk of ovarian diseases: a two-sample Mendelian randomization study

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