Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, Foshan, China.
TCM Gynecology Department, Foshan Fosun Chancheng Hospital, Chancheng District, Foshan, China.
Front Endocrinol (Lausanne). 2024 Apr 22;15:1368334. doi: 10.3389/fendo.2024.1368334. eCollection 2024.
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.
研究表明，肠道微生物群与男性不育（MI）有关。然而，它们的因果关系和潜在的中介需要更多的证据来证明。我们旨在通过孟德尔随机化方法从遗传角度研究肠道微生物组与 MI 之间的因果关系以及炎症细胞因子的潜在中介作用。
本研究使用了来自肠道微生物（Mibiogen，n=18,340）、炎症细胞因子（NFBC1966、FYPCRS、FINRISK 1997 和 2002，n=13,365）和男性不育（Finngen，n=120,706）的全基因组关联研究的数据，进行了双向孟德尔随机化（MR）、中介 MR 和多变量 MR（MVMR）分析。在本研究中，逆方差加权法被用作主要分析方法，其他方法被用作补充分析方法。
本研究发现，两种肠道微生物和两种炎症细胞因子与 MI 有潜在的因果关系。与男性不育相关的两种肠道微生物中，Anaerotruncus 增加了男性不育的风险（比值比=1.81，95%置信区间=1.18-2.77，P=0.0062），Bacteroides 降低了男性不育的风险（比值比=0.57，95%置信区间=0.33-0.96，P=0.0363）。此外，在所确定的两种炎症细胞因子中，肝细胞生长因子（HGF）降低了男性不育的风险（比值比=0.50，95%置信区间=0.35-0.71，P=0.0001），单核细胞趋化蛋白 3（MCP-3）增加了男性不育的风险（比值比=1.28，95%置信区间=1.03-1.61，P=0.0039）。中介 MR 分析表明，HGF 介导了 Bacteroides 对 MI 的因果效应（中介百分比为 38.9%）。多变量 MR 分析表明，HGF 可能是 Bacteroides 影响 MI 的途径之一，还有其他未被探索的途径。
本研究表明，特定的肠道微生物群、炎症细胞因子与 MI 之间存在因果关系。此外，HGF 可能介导了 Bacteroides 与 MI 的关系。
