Causal effects of gut microbiota on erectile dysfunction: a two-sample Mendelian randomization study.

Area of Science:

• Microbiome research
• Genetics
• Urology
• Gastroenterology

Background:

• Observational studies suggest a link between gut microbiota and erectile dysfunction (ED).
• Previous research faced limitations like confounding factors and reverse causality, hindering causal inference.
• Establishing a causal relationship is crucial for understanding ED pathogenesis and developing targeted therapies.

Purpose of the Study:

• To determine the causal effect of gut microbiota on the risk of erectile dysfunction (ED).
• To leverage Mendelian randomization (MR) to overcome limitations of observational studies.
• To identify specific gut bacteria associated with increased or decreased risk of ED.

Main Methods:

• A two-sample Mendelian randomization (MR) study utilizing genome-wide association study (GWAS) summary-level data.
• Gut microbiota data from MiBioGen (N=18,340) and ED data from IEU Open GWAS (6,175 cases, 217,630 controls).
• Inverse variance weighted (IVW) approach as primary analysis, with sensitivity analyses (Cochran's Q, MR-Egger, MR-PRESSO) to ensure robustness.

Main Results:

• Increased abundance of *Lachnospiraceae* (family), *Senegalimassilia*, *Lachnospiraceae NC2004* group, *Tyzzerella3*, and *Oscillibacter* (genera) associated with increased ED risk.
• Increased abundance of *Ruminococcaceae UCG013* (genus) showed a protective effect against ED.
• Sensitivity analyses confirmed no significant heterogeneity or horizontal pleiotropy, supporting the validity of the findings.

Conclusions:

• Gut microbiota exerts both inducing and protective causal effects on the risk of erectile dysfunction (ED).
• Findings offer novel insights for clinicians in the future treatment and prevention strategies for ED.
• This study advances the understanding of microbiota-mediated ED pathogenesis.