Genetic insights into gut microbiota and risk of prostatitis: a Mendelian randomization study

Abstract

Background: The dysbiosis of gut microbiota (GM) is considered a contributing factor to prostatitis, yet the causality remains incompletely understood.

Methods: The genome-wide association study (GWAS) data for GM and prostatitis were sourced from MiBioGen and FinnGen R10, respectively. In the two-sample Mendelian randomization (MR) analysis, inverse variance weighting (IVW), MR-Egger, weighted median, simple mode, weighted mode, and maximum likelihood (ML) methods were utilized to investigate the causal relationship between GM and prostatitis. A series of sensitivity analysis were conducted to confirm the robustness of the main results obtained from the MR analysis.

Results: According to the IVW results, genus Sutterella (OR: 1.37, 95% CI: 1.09-1.71, p = 0.006) and genus Holdemania (OR: 1.21, 95% CI: 1.02-1.43, p = 0.028) were associated with an increased risk of prostatitis. The phylum Verrucomicrobia (OR: 0.76, 95% CI: 0.58-0.98, p = 0.033) and genus Parasutterella (OR: 0.84, 95% CI: 0.70-1.00, p = 0.045) exhibited a negative association with prostatitis, indicating a potential protective effect. Sensitivity analysis showed that these results were not affected by heterogeneity and horizontal pleiotropy. Furthermore, the majority of statistical methods yielded results consistent with those of the IVW analysis.

Conclusions: In this study, we identified two GM taxon that might be protective against prostatitis and two GM taxon that could increase the risk of developing prostatitis. These findings could potentially provide a valuable theoretical basis for the future development of preventive and therapeutic strategies for prostatitis.

Keywords: Mendelian randomization; causal relationship; genome-wide association study; gut microbiota; prostatitis.

Figure 1

Overview of the MR analysis process. IV, instrumental variable; SNP, single nucleotide polymorphism; MR, Mendelian randomization; MR-PRESSO, Mendelian randomization pleiotropy residual sum and outlier.

Figure 2

MR results of casual links between specific gut microbiota taxa and prostatitis risk. nSNP, number of single nucleotide polymorphism.

Figure 3

Scatter plots illustrating the causal effect of gut microbiota on prostatitis.

Figure 4

Leave-one-out analysis for the effect of individual SNPs on the correlation between the GM taxa and the risk of prostatitis. The horizontal axis represents the effect of the GM on the risk of prostatitis after excluding individual SNP. The vertical axis represents the individual SNP that have been excluded. The red line represents the overall effect of all SNPs. The dots represent the odds ratio values, the horizontal lines represent the 95% confidence intervals.