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

Frontiers in endocrinology (Lausanne), 2024, Vol.15, p.1368334-1368334 [Peer Reviewed Journal]

Copyright © 2024 Zou, Xu, Xu, Xing, Chen and Wu. ;Copyright © 2024 Zou, Xu, Xu, Xing, Chen and Wu 2024 Zou, Xu, Xu, Xing, Chen and Wu ;ISSN: 1664-2392 ;EISSN: 1664-2392 ;DOI: 10.3389/fendo.2024.1368334 ;PMID: 38711980

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  • Title:
    Inflammatory cytokines may mediate the causal relationship between gut microbiota and male infertility: a bidirectional, mediating, multivariate Mendelian randomization study
  • Author: Zou, Haoxi ; Xu, Ningning ; Xu, Huanying ; Xing, Xiaoyan ; Chen, Yanfen ; Wu, Suzhen
  • Subjects: Adult ; causal inference ; Cytokines - genetics ; Cytokines - metabolism ; Endocrinology ; Gastrointestinal Microbiome ; genetics ; Genome-Wide Association Study ; gut microbes ; Humans ; Infertility, Male - genetics ; Infertility, Male - microbiology ; Inflammation - microbiology ; inflammatory cytokine ; Male ; male infertility ; Mendelian randomization ; Mendelian Randomization Analysis ; Polymorphism, Single Nucleotide
  • Is Part Of: Frontiers in endocrinology (Lausanne), 2024, Vol.15, p.1368334-1368334
  • Description: Studies 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. This 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. In 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. The 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.
  • Publisher: Switzerland: Frontiers Media S.A
  • Language: English
  • Identifier: ISSN: 1664-2392
    EISSN: 1664-2392
    DOI: 10.3389/fendo.2024.1368334
    PMID: 38711980
  • Source: PubMed Central (Open access)
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    Geneva Foundation Free Medical Journals at publisher websites
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    ROAD: Directory of Open Access Scholarly Resources
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