Previous research has suggested that infectious pathogens are associated with benign prostatic disease (BPD). This study employs Generalized Summary data-based Mendelian Randomization (GSMR) to explore causal relationships between pathogen-derived antibodies and benign prostatic diseases.

We performed robust statistical methods including a bidirectional GSMR to investigate the causal effects between pathogen-derived antibodies and BPD, and additional MR methods including IVW random effects (IVW-RE), MR-Egger regression were applied to examine the antibody-disease relationships from the main analysis of GSMR.

The Epstein-Barr virus (EBNA-1) antibody levels were significantly associated with a higher risk of BPH (OR=1.08, 95%CI=1.04–1.13, p-value=8.2 × 10-5), similar findings were also observed in the corresponding inverse-variance weighted (IVW) analysis(OR=1.08, 95%CI=1.04–1.13, p-value=0.3 × 10-3). Conversely, higher Epstein-Barr virus ZEBRA antibody levels were associated with a potential protective effect of BPH(OR=0.93, 95%CI=0.89–0.97, p-value=1.8 × 10-3), the same trend was also evident in the IVW analysis.Furthermore, reverse GSMR and MR indicated that BPH could increase the levels of Helicobacter pylori OMP antibody and the seropositivity of Anti-chlamydia trachomatis IgG.

This study clarifies the complex role of pathogen antibodies in benign prostate diseases, uncovering substantial implications for translational therapeutic development. The results underscore the need for deeper exploration of pathogen-immune system interactions to guide precision intervention strategies.