肠道微生物群与前列腺癌之间的潜在关系（可能受到免疫细胞的影响）仍不清楚。本研究采用中介孟德尔随机化 (MR) 技术来研究肠道微生物群、免疫细胞和前列腺癌之间的因果关系。免疫细胞活性数据来自 Valeria Orrù 的研究，而全基因组关联研究结果数据集则来自综合流行病学单位数据库。双向 MR 分析采用 5 种不同的方法：逆方差加权 (IVW)、加权中值、MR-Egger 回归、加权模式和简单模式。此外，还利用中介分析探讨了免疫细胞对肠道微生物群和前列腺癌的中介作用。筛选了与前列腺癌相关的八十三个单核苷酸多态性作为工具变量。在以肠道微生物群作为暴露因素的阳性 MR 分析中，IVW 显示 8 种肠道微生物群与前列腺癌之间存在关联。此外，使用 IVW 等方法发现 9 种类型的免疫细胞与前列腺癌相关。对免疫细胞 (beta1) 上肠道微生物群的 MR 分析显示，双歧杆菌和 CD39 T 调节细胞 (Tregs；比值比 [OR] = 0.785，95% 置信区间 [CI] = 0.627-0.983，P = .03 ）。此外，前列腺癌疾病（β2）中免疫细胞的MR分析显示CD39 Tregs是前列腺癌的危险因素（OR = 1.215，95% CI = 1.027-1.354，P = .04）。此外，前列腺癌肠道菌群的MR分析（总效应）表明双歧杆菌是前列腺癌的保护因子（OR = 0.905，95% CI = 0.822-0.977，P = .04）。敏感性分析验证了上述结果的稳健性。中介分析表明，CD39 Tregs 部分介导双歧杆菌与前列腺癌之间的因果关系。本研究证明双歧杆菌通过CD39 Tregs作为介质抑制前列腺癌进展，为前列腺癌的治疗和预防提供新的思路和方法。版权所有©2024。由 Wolters Kluwer Health, Inc. 出版

The potential relationship between the gut microbiota and prostate cancer, possibly influenced by immune cells, remains unclear. This study employed the mediation Mendelian randomization (MR) technique to investigate the causal link between the gut microbiota, immune cells, and prostate cancer. Data on immune cell activity were sourced from Valeria Orrù's research, whereas the genome-wide association study outcome dataset was obtained from the Integrative Epidemiology Unit database. The bidirectional MR analysis utilized 5 different methods: inverse variance weighted (IVW), weighted median, MR-Egger regression, weighted mode, and simple mode. In addition, the mediating effect of immune cells on the gut microbiota and prostate cancer was explored using mediation analysis. Eighty-three single nucleotide polymorphisms associated with prostate cancer were screened as instrumental variables. In a positive MR analysis with gut microbiota as the exposure factor, IVW showed an association between 8 gut microbiota and prostate cancer. Additionally, 9 types of immune cells have been found to be associated with prostate cancer using methods such as IVW. MR analysis of the gut microbiota on immune cells (beta1) revealed a negative correlation between Bifidobacterium and CD39+ T regulatory cells (Tregs; odds ratio [OR] = 0.785, 95% confidence interval [CI] = 0.627-0.983, P = .03). Furthermore, MR analysis of immune cells in prostate cancer disease (beta2) showed that CD39+Tregs are a risk factor for prostate cancer (OR = 1.215, 95% CI = 1.027-1.354, P = .04). Moreover, MR analysis of gut microbiota in prostate cancer (total effect) indicated that Bifidobacterium is a protective factor for prostate cancer (OR = 0.905, 95% CI = 0.822-0.977, P = .04). The sensitivity analysis verified the robustness of the above results. Mediation analysis demonstrated that CD39+Tregs partially mediate the causal relationship between Bifidobacterium and prostate cancer. This study demonstrates that Bifidobacterium inhibits prostate cancer progression through CD39+Tregs as mediators, providing new ideas and approaches for the treatment and prevention of prostate cancer.Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.