Assessing the relationship between gut microbiota and hyperprolactinemia: A bidirectional two-sample Mendelian randomization study

The relationship between hyperprolactinemia and gut microbiota remains unclear at present. This study employs a Mendelian randomization (MR) approach to assess the potential causal links between gut microbiota and the incidence of hyperprolactinemia. Genetic instrumental variables associated with gut microbiota were identified through a genome-wide association study involving 18,340 participants. Summary statistics regarding hyperprolactinemia were obtained from FinnGen R10, comprising 1099 cases and 395,289 controls. The primary analysis utilized the inverse-variance weighted method. Additionally, we employed the weighted-median method, MR-Egger regression, and MR pleiotropy residual sum and outlier test to validate the robustness of our findings. Subsequently, a reverse MR analysis was conducted to assess the potential for reverse causation. We identified suggestive associations between 7 bacterial traits and the risk of hyperprolactinemia (odds ratio [OR]: 0.685; 95% confidence interval [CI]: 0.483 to 0.97; P = .033 for Family Bacteroidales S24.7; OR: 1.589; 95% CI: 1.057 to 2.389; P = .026 for Genus Ruminococcus gauvreauii group; OR: 0.686; 95% CI: 0.522 to 0.901; P = .007 for Genus Anaerofilumgroup; OR: 1.333; 95% CI: 1.017 to 1.747; P = .037 for Genus Eisenbergiella group; OR: 0.595; 95% CI: 0.416 to 0.852; P = .005 for Genus Erysipelotrichaceae UCG003 group; OR: 1.3986; 95% CI: 1.00 to 1.954; P = .005 for Genus Ruminococcaceae UCG014 group and OR: 0.781; 95% CI: 0.612 to 0.998; P = .048 for Genus Peptococcus group).We did not find statistically significant associations between hyperprolactinemia and these 7 bacterial traits in the reverse MR analysis. Our systematic analysis provides evidence supporting a potential causal relationship between specific gut microbiota taxa and the risk of hyperprolactinemia.