先前的研究已经建立了肠道微生物群组成的改变与各种妇科肿瘤之间的关联。然而，建立肠道微生物群与这些肿瘤之间的因果关系仍然是必要的。本研究采用两个样本孟德尔随机化 (MR) 方法来研究因果关系，旨在识别可能参与妇科肿瘤发展的致病菌群落。MiBioGen 联盟的肠道微生物群全基因组关联研究 (GWAS) 的数据被用作暴露变量。选择四种常见的妇科肿瘤作为结果变量，包括子宫肌瘤（UF）、子宫内膜癌（EC）、卵巢癌（OC）和宫颈癌（CC）。选择与肠道微生物群显着相关的单核苷酸多态性（SNP）作为工具变量（IV）。使用逆方差加权 (IVW) 方法作为主要 MR 分析来评估因果关系。外部验证是使用独立机构进行的。进行敏感性分析以确保稳健性。还进行了反向 MR 分析以评估潜在的反向因果关系。结合发现和验证队列，我们​​发现 Lachnospiraceae 的相对丰度较高与较低的 UF 风险相关（OR：0.882，95％CI：0.793-0.982，P = 0.022）。相反，较高的 OC 发病率与毛螺菌科相对丰度增加相关（OR：1.329，95% CI：1.019-1.732，P = 0.036）。敏感性分析证实了这些发现的可靠性。反向 MR 分析显示，没有证据表明 UF、OC 和 Lachnospiraceae 之间存在反向因果关系。本研究建立了 Lachnospiraceae 相对丰度与 UF 和 OC 之间的因果关系。这些发现为肠道微生物群在妇科肿瘤发展机制中的潜在作用提供了新的见解。版权所有 © 2024 Xiong、Zhang、Niu、Zhang、Sheng 和 Xu。

Previous research has established associations between alterations in gut microbiota composition and various gynecologic tumors. However, establishing a causal relationship between gut microbiota and these tumors remains necessary. This study employs a two-sample Mendelian randomization (MR) approach to investigate causality, aiming to identify pathogenic bacterial communities potentially involved in gynecologic tumor development.Data from the MiBioGen consortium's Genome-Wide Association Study (GWAS) on gut microbiota were used as the exposure variable. Four common gynecologic neoplasms, including uterine fibroids (UF), endometrial cancer (EC), ovarian cancer (OC), and cervical cancer (CC), were selected as outcome variables. Single-nucleotide polymorphisms (SNPs) significantly associated with gut microbiota were chosen as instrumental variables (IVs). The inverse variance-weighted (IVW) method was used as the primary MR analysis to assess the causal relationship. External validation An was conducted using an independent. Sensitivity analyses were performed to ensure robustness. Reverse MR analysis was also conducted to assess potential reverse causation.Combining discovery and validation cohorts, we found that higher relative abundance of Lachnospiraceae is associated with lower UF risk (OR: 0.882, 95% CI: 0.793-0.982, P = 0.022). Conversely, higher OC incidence is associated with increased relative abundance of Lachnospiraceae (OR: 1.329, 95% CI: 1.019-1.732, P = 0.036). Sensitivity analyses confirmed these findings' reliability. Reverse MR analysis showed no evidence of reverse causation between UF, OC, and Lachnospiraceae.This study establishes a causal relationship between Lachnospiraceae relative abundance and both UF and OC. These findings provide new insights into the potential role of gut microbiota in mechanisms underlying gynecological tumors development.Copyright © 2024 Xiong, Zhang, Niu, Zhang, Sheng and Xu.