关键词: Mendelian randomization diagnosis erectile dysfunction gut microbiota prevention

Mesh : Male Humans Gastrointestinal Microbiome Erectile Dysfunction / etiology genetics Mendelian Randomization Analysis Actinobacteria Clostridiales

来  源:   DOI:10.3389/fendo.2023.1216746   PDF(Pubmed)

Abstract:
UNASSIGNED: Studies have found that gut microbiota may be associated with the development of erectile dysfunction (ED); however, the exact link between the two remains unclear. This study aimed to elucidate the relationship between the gut microbiota and the risk of ED from a genetic perspective.
UNASSIGNED: We investigated the relationship between the gut microflora and ED using two-sample Mendelian randomization. GWAS-pooled data for ED were obtained from 223805 participants in Europe. GWAS summary data for ED were obtained from 223805 subjects in Europe and that for the gut microbiota were obtained from 18340 participants in 24 cohorts. We used the inverse-variance weighted (IVW) estimator as the primary method for the preliminary analysis, and the MR-Egger, weighted median (WM), simple model, and weighted model as secondary methods. We used Cochrane\'s Q-test, to detect heterogeneity, MREgger to detect pleiotropy, and the leave-one-out method to test the stability of the MR results. Ultimately, we genetically predicted a causal relationship between 211 gut microbiota and ED.
UNASSIGNED: A total of 2818 SNPs associated with gut microflora were screened in the ED correlation analysis based on the assumption of instrumental variables. The results of MR analysis showed a causal relationship between the six gut microbes and ED occurrence. The results of the fixed effects IVW method revealed five gut microflora, including Lachnospiraceae (OR, 1.265; P = 0.008), Lachnospiraceae NC2004 group (OR, 1.188; P = 0.019), Oscillibacter (OR, 1.200; P = 0.015), Senegalimassilia (OR, 1.355; P = 0.002), Tyzzerella3 (OR, 1.133; P = 0.022), to be negatively associated with ED. In addition, the IVW method revealed Ruminococcaceae UCG-013 (OR, 0.827; P = 0.049) to be positively associated with ED. Quality control results showed no heterogeneity or horizontal pleiotropy in the MR analysis (P > 0.05).
UNASSIGNED: Six gut microbes were genetically associated with ED; of which, Ruminococcaceae UCG-013 was causally associated with a reduced risk of ED development. Our findings provide a new direction for research on the prevention and treatment of ED; however, the mechanisms and details require further investigation.
摘要:
研究发现,肠道菌群可能与勃起功能障碍(ED)的发展有关;然而,两者之间的确切联系尚不清楚。本研究旨在从遗传角度阐明肠道菌群与ED风险之间的关系。
我们使用双样本孟德尔随机化研究了肠道菌群与ED之间的关系。ED的GWAS汇总数据来自223805名欧洲参与者。ED的GWAS汇总数据来自欧洲223805名受试者,肠道微生物群的汇总数据来自24个队列的18340名参与者。我们使用逆方差加权(IVW)估计器作为初步分析的主要方法,和MR-Egger,加权中位数(WM),简单的模型,和加权模型作为次要方法。我们用了Cochrane的Q检验,为了检测异质性,MREgger来检测多效性,和留一法检验MR结果的稳定性。最终,我们从基因上预测了211个肠道菌群与ED之间的因果关系.
基于工具变量的假设,在ED相关性分析中筛选了总共2818个与肠道菌群相关的SNP。MR分析结果表明,六种肠道微生物与ED发生之间存在因果关系。固定效应IVW方法的结果揭示了五种肠道菌群,包括落叶松科(或,1.265;P=0.008),落叶松科NC2004组(OR,1.188;P=0.019),镰刀菌(或,1.200;P=0.015),塞内加尔(或,1.355;P=0.002),Tyzzerella3(或,1.133;P=0.022),与ED呈负相关。此外,IVW方法显示了RuminoccaceaeUCG-013(或,0.827;P=0.049)与ED呈正相关。质量控制结果在MR分析中无异质性或水平多效性(P>0.05)。
六种肠道微生物与ED遗传相关;其中,RuminoccaceaeUCG-013与ED发展风险降低有因果关系。我们的发现为ED的防治研究提供了新的方向,机制和细节需要进一步调查。
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