Causal relationships between gut microbiota and male reproductive inflammation and infertility: Insights from Mendelian randomization

Abstract

The study observed interactions between gut microbiota and male reproductive health, noting that the causal relationships were previously unclear. It aimed to explore the potential cause-and-effect relationship between gut bacteria and male reproductive problems such as inflammation, infertility, and sperm functionality, using a two-sample Mendelian randomization method to examine these connections. The analysis found that certain bacterial genera, such as Erysipelatoclostridium (0.71 [0.55-0.92]), Parasutterella (0.74 [0.57-0.96]), Ruminococcaceae UCG-009 (0.77 [0.60-0.98]), and Slackia (0.69 [0.49-0.96]), showed protective effects against prostatitis. In contrast, other genera like Faecalibacterium (1.59 [1.08-2.34]), Lachnospiraceae UCG004 (1.64 [1.15-2.34]), Odoribacter (1.68 [1.01-2.81]), Paraprevotella (1.28 [1.03-1.60]), and Sutterella (1.58 [1.13-2.19]) were detrimental. Additionally, causal relationships were identified between 2 genera and orchitis and epididymitis, 3 genera and male infertility, and 5 genera and abnormal spermatozoa. Further analysis of sperm-related proteins revealed causal associations between specific bacterial genera and proteins such as SPACA3, SPACA7, SPAG11A, SPAG11B, SPATA9, SPATA20, and ZPBP4. The results remained robust after sensitivity analysis and reverse Mendelian randomization analysis. The study concluded that specific bacterial genera have causal roles in reproductive inflammation, infertility, and sperm-associated proteins. This provides a novel strategy for the early diagnosis and identification of therapeutic targets in reproductive inflammation and infertility.

Keywords: Mendelian randomization; gut microbiota; infertility; prostatitis; sperm-related proteins.

Figure 1.

Study design and workflow. GWAS = genome-wide association studies; IVs = instrumental variables; IVW = inverse-variance weighting; MR = Mendelian randomization; SNPs = single nucleotide polymorphisms.

Figure 2.

MR results of causal links between gut microbiome and inflammation of the male reproductive inflammation and infertility. CI = confidence intervals; IVW = inverse-variance weighting; OR = odds ratios; SNPs = single nucleotide polymorphisms.

Figure 3.

Scatter plot of the causal association between gut microbiome and prostatitis. SNPs = single nucleotide polymorphisms.

Figure 4.

MR results of causal links between gut microbiome and sperm-related proteins. CI = confidence intervals; IVW = inverse-variance weighting; OR = odds ratios; SNPs = single nucleotide polymorphisms.

Figure 5.

Leave-one-out analysis of the causal association between gut microbiome and prostatitis.