Causal association of the skin microbiome with human infertility: insights from a bidirectional two-sample Mendelian randomization

Infertility is a disorder characterized by the inability to achieve a clinical pregnancy after 12 months of regular and unprotected sexual activity. Affecting 8-12% of the global population, with the continuous progress of microbial research in recent years, a variety of microorganisms may be associated with the onset of infertility. We therefore used a two-sample MR Analysis to investigate the association between skin microbes and infertility. we used preprocessed exposure data to correlate infertility measures (infertility in women, associated with anovulation; Female infertility, cervical infertility, vaginal infertility, other infertility or unknown causes; Female infertility, fallopian tube origin; ED; Based on this, the positive results were subjected to horizontal pleiotropy analysis and heterogeneity analysis. Finally, Steiger test was performed to confirm the absence of reverse causality. The data used in this study were obtained from the published GWAS data sets. skin microbiota from the study conducted by Moitinho-Silva et al., and the exposure from the Finn. In this study, we found a positive causal association between Lactobacillales, Clostridiales, Pseudomonadales, and Moraxellaceae and female infertility and anovulation by MR Analysis of two samples. Enhydrobacter, Betaproteobacteria have a negative causal association with female infertility and anovulation. Lactobacillales and Alphaproteobacteria had positive causal association with female infertility, cervical infertility, vaginal infertility, other infertility or unknown causes. There was a negative causal association between Haemophilus and female infertility, cervical infertility, vaginal infertility, other infertility or unknown causes. Alphaproteobacteria are positively correlated with female infertility and fallopian tube origin. Bacteroidetes is negatively correlated with female infertility and fallopian tube origin. Rhodobacteraceae, Clostridiales and Flavobacteriaceae had a negative causal association with male infertility. Corynebacterium had a positive causal association with ED, and Micrococcus had a negative causal association with ED. Our study reveals a causal association between skin microbiota and infertility, and provides a theoretical basis for the inclusion of skin microbiota in the prevention and treatment of infertility. To the best of our knowledge, our study is the first MR Analysis to explore the potential causal association between skin microbiota and infertility. On this basis, we make a reasonable hypothesis that skin microbes cause infertility, and propose possible mechanisms. Our research contributes to the prevention and treatment of clinical infertility.