Abstract
The study investigates the causal relationship between gut microbes and female genital tract polyps, exploring the potential mediating role of immune cells via Mendelian randomization (MR) analysis. Our MR study was designed following the STROBE-MR guidelines. We combined data from a large-scale GWAS meta-analysis, including 731 immune profiles and female genital tract polyps, with gut microbiology data sourced from the MiBioGen consortium. Univariate Mendelian randomization was employed to identify gut microbes and immune profiles significantly associated with female genital tract polyps causally. A 2-step MR analysis was utilized to investigate the potential mediating role of immune cells. Furthermore, we utilized the multivariable MR approach based on Bayesian model averaging (MR-BMA) to further assess the prioritization of gut microbiota vs immune characteristics in the development of female genital tract polyps. Through univariate MR analysis, we identified a significant causal link between 12 gut microbiota, 31 immune features, and female genital tract polyps. Four causal pathways involving gut microbiota, immune cells, and polyps were identified among them. MR-BMA analysis indicated marginal inclusion probability (MIP) values exceeding 0.1 for 5 gut microbiota groups: Victivallaceae (model-averaged causal estimate [MACE] = 0.060, MIP = 0.581, P = .0089), Ruminococcus gautreuii (MACE = 0.052, MIP = 0.346, P = .0640), Lachnoclostrium (MACE = 0.0380, MIP = 0.225, P = .1875), Alphaprobacter (MACE = 0.0186, MIP = 0.140, P = .3934), and Fusicatenibacter (MACE = 0.013, MIP = 0.110, P = .5818). Six immune features exhibit high priority, with MIP values exceeding 0.5, including HLA DR on CD33+ HLA DR+ CD14dim (MACE = -0.015, MIP = 0.753, P = .0853), HVEM on naive CD4+ T cell (MACE = 0.024, MIP = 0.737, P = .0053), CD80 on CD62L+ plastic cytoplasmic dendritic cell (MACE = 0.024, MIP = 0.721, P = .0228), CD28 on activated and secret CD4 regulatory T cell (MACE = 0.0054, MIP = 0.706, P = .3245), HLA DR on CD14+ CD16 monocyte (MACE = -0.0003, MIP = 0.520, P = .7927), HLA DR on CD14+ monocyte (MACE = -0.0029, MIP = 0.509, P = .5576). Our research indicates that gut microbiota exerts an independent causal influence on female genital tract polyps, potentially impacting them via various immune cells.