Jia Ran, Fu Yuhang, Xue Miaomiao, Zhou Cheng, Jin Jie
The First College of Clinical Medicine, Henan University of Chinese Medicine, Zhengzhou, China.
Department of Gastroenterology, Changzhou Hospital of Traditional Chinese Medicine, Changzhou, China.
Medicine (Baltimore). 2024 Dec 6;103(49):e40833. doi: 10.1097/MD.0000000000040833.
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.
该研究通过孟德尔随机化（MR）分析，探讨肠道微生物群与女性生殖道息肉之间的因果关系，以及免疫细胞的潜在中介作用。我们的MR研究是按照STROBE-MR指南设计的。我们将来自大规模全基因组关联研究（GWAS）荟萃分析的数据（包括731个免疫特征和女性生殖道息肉）与来自MiBioGen联盟的肠道微生物学数据相结合。采用单变量孟德尔随机化来确定与女性生殖道息肉有因果关系的肠道微生物群和免疫特征。利用两步MR分析来研究免疫细胞的潜在中介作用。此外，我们基于贝叶斯模型平均法（MR-BMA）采用多变量MR方法，进一步评估肠道微生物群与免疫特征在女性生殖道息肉发生发展中的优先级。通过单变量MR分析，我们确定了12种肠道微生物群、31种免疫特征与女性生殖道息肉之间存在显著的因果关系。其中发现了4条涉及肠道微生物群、免疫细胞和息肉的因果途径。MR-BMA分析表明，5个肠道微生物群的边际包含概率（MIP）值超过0.1：Victivallaceae（模型平均因果估计[MACE]=0.060，MIP=0.581，P=0.0089）、戈氏瘤胃球菌（MACE=0.052，MIP=0.346，P=0.0640）、迟缓真杆菌属（MACE=0.0380，MIP=0.225，P=0.1875）、α变形杆菌属（MACE=0.0186，MIP=0.140，P=0.3934）和梭菌属（MACE=0.013，MIP=0.110，P=0.5818）。6种免疫特征具有高优先级，MIP值超过0.5，包括CD33+HLA DR+CD14dim细胞上的HLA DR（MACE=-0.015，MIP=0.753，P=0.0853）、初始CD4+T细胞上的疱疹病毒进入介质（HVEM）（MACE=0.024，MIP=0.737，P=0.0053）、CD62L+可塑性细胞质树突状细胞上的CD80（MACE=0.024，MIP=0.721，P=0.0228）、活化分泌型CD4调节性T细胞上的CD28（MACE=0.0054，MIP=0.706，P=0.3245）、CD14+CD16单核细胞上的HLA DR（MACE=-0.0003，MIP=0.520，P=0.7927）、CD14+单核细胞上的HLA DR（MACE=-0.0029，MIP=0.509，P=0.5576）。我们的研究表明，肠道微生物群对女性生殖道息肉有独立的因果影响，可能通过多种免疫细胞对其产生影响。
