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评估肠道微生物群与前列腺癌之间的因果关系:一项两样本孟德尔随机化研究。

Assessing the causal relationship between gut microbiota and prostate cancer: A two-sample Mendelian randomization study.

作者信息

Wang Yijie, Long Zhaohui, Hong Yulong, Zhou Xing, Yang Guang, Tang Cheng, Qu Genyi, Li Yuan

机构信息

Department of Urology, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, Hunan, China.

Department of Urology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

出版信息

Urol Oncol. 2025 Mar;43(3):190.e1-190.e10. doi: 10.1016/j.urolonc.2024.10.007. Epub 2024 Oct 24.

Abstract

BACKGROUND

Numerous studies indicate that the gut microbiome is closely associated with prostate cancer (PCa), however, owing to various confounding factors, the causal relationship between gut microbiota and PCa remains unclear.

METHODS

A 2-sample Mendelian randomization (MR) analysis utilized genome-wide association study (GWAS) data on the gut microbiota of 18,340 participants and GWAS summary statistics on PCa involving 46,3010 participants. Inverse variance weighted (IVW) served as the primary method, complemented by the MR-Egger method, weighted median method (WME), simple mode method (SM), and weighted mode method (WM). Finally, to confirm the robustness of the results, heterogeneity test, pleiotropy test, and leave-one-out sensitivity test were conducted.

RESULTS

IVW analysis revealed that 12 specific gut microbial taxa were potentially causally associated with PCa; the genera Victivallis, Akkermansia, Odoribacter, Butyrivibrio, and the families Enterobacteriaceae, Verrucomicrobiaceae, as well as the orders Verrucomicrobiales, Enterobacteriales and the class Verrucomicrobiae, were found to be positively associated with PCa risk. Conversely, the genera Eubacterium ruminantium group, Candidatus Soleaferrea, and RuminococcaceaeUCG003 were negatively associated with PCa risk.

CONCLUSIONS

Our MR study's results support a genetically predicted causal relationship between the gut microbiota and PCa, and we identified 12 specific gut microbial taxa. These findings could offer new targets for PCa screening and treatment.

摘要

背景

众多研究表明肠道微生物群与前列腺癌(PCa)密切相关,然而,由于各种混杂因素,肠道微生物群与PCa之间的因果关系仍不清楚。

方法

采用两样本孟德尔随机化(MR)分析,利用18340名参与者的肠道微生物群全基因组关联研究(GWAS)数据以及涉及463010名参与者的PCa的GWAS汇总统计数据。逆方差加权(IVW)作为主要方法,辅以MR-Egger方法、加权中位数方法(WME)、简单模式方法(SM)和加权模式方法(WM)。最后,为了确认结果的稳健性,进行了异质性检验、多效性检验和留一法敏感性检验。

结果

IVW分析显示,12种特定的肠道微生物分类群可能与PCa存在因果关系;发现Victivallis属、Akkermansia属菌、Odoribacter属菌、丁酸弧菌属以及肠杆菌科、疣微菌科,以及疣微菌目、肠杆菌目和疣微菌纲与PCa风险呈正相关。相反,瘤胃真杆菌群、暂定索氏菌属和瘤胃球菌科UCG003与PCa风险呈负相关。

结论

我们的MR研究结果支持肠道微生物群与PCa之间存在基因预测的因果关系,并且我们鉴定出了12种特定的肠道微生物分类群。这些发现可为PCa的筛查和治疗提供新的靶点。

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