Causal relationships of gut microbiota and blood metabolites with ovarian cancer and endometrial cancer: a Mendelian randomization study.

IF 3.8 3区医学 Q1 REPRODUCTIVE BIOLOGY

Journal of Ovarian Research Pub Date : 2025-03-13 DOI:10.1186/s13048-025-01630-5

Jinyan Chen, Xuejun Chen, Jiong Ma

{"title":"Causal relationships of gut microbiota and blood metabolites with ovarian cancer and endometrial cancer: a Mendelian randomization study.","authors":"Jinyan Chen, Xuejun Chen, Jiong Ma","doi":"10.1186/s13048-025-01630-5","DOIUrl":null,"url":null,"abstract":"Objectives: The study aimed to investigate the causal relationships of gut microbiota (GM), ovarian cancer (OC), endometrial cancer (EC), and potential metabolite mediators using Mendelian randomization (MR) analysis.Methods: Bidirectional two-sample MR analysis and reverse MR analysis of GM on OC/EC were employed to determine the causal effects of GM on OC/EC and the mediating role of blood metabolites in the relationship between GM and OC/EC, with results validated through sensitivity analysis.Results: We identified 6 pathogenic bacterial taxa associated with OC, including Euryarchaeota, Escherichia-Shigella, FamilyXIIIAD3011group, Prevotella9, and two unknown genera. Christensenellaceae R.7group, Tyzzerella3, and Victivallaceae were found to be protective against OC. The increase in EC risk was positively associated with Erysipelotrichia, Erysipelotrichaceae, Erysipelotrichales, and FamilyXI. Dorea, RuminococcaceaeUCG014, and Turicibacter exhibited a negative correlation with the EC risk. A total of 26 and 19 blood metabolites related to GM were identified, showing significant correlations with OC and EC, respectively. Cytosine was found to be an intermediate metabolite greatly associated with EC and FamilyXI. In reverse MR analysis, the FamilyXIIIAD3011group exhibited a significant bidirectional causal relationship with OC.Conclusion: Our study revealed causal relationships of GM and intermediate metabolites with OC/EC, providing new avenues for understanding OC/EC and developing effective treatment strategies.","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"54"},"PeriodicalIF":3.8000,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11905533/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Ovarian Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13048-025-01630-5","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"REPRODUCTIVE BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Objectives: The study aimed to investigate the causal relationships of gut microbiota (GM), ovarian cancer (OC), endometrial cancer (EC), and potential metabolite mediators using Mendelian randomization (MR) analysis.

Methods: Bidirectional two-sample MR analysis and reverse MR analysis of GM on OC/EC were employed to determine the causal effects of GM on OC/EC and the mediating role of blood metabolites in the relationship between GM and OC/EC, with results validated through sensitivity analysis.

Results: We identified 6 pathogenic bacterial taxa associated with OC, including Euryarchaeota, Escherichia-Shigella, FamilyXIIIAD3011group, Prevotella9, and two unknown genera. Christensenellaceae R.7group, Tyzzerella3, and Victivallaceae were found to be protective against OC. The increase in EC risk was positively associated with Erysipelotrichia, Erysipelotrichaceae, Erysipelotrichales, and FamilyXI. Dorea, RuminococcaceaeUCG014, and Turicibacter exhibited a negative correlation with the EC risk. A total of 26 and 19 blood metabolites related to GM were identified, showing significant correlations with OC and EC, respectively. Cytosine was found to be an intermediate metabolite greatly associated with EC and FamilyXI. In reverse MR analysis, the FamilyXIIIAD3011group exhibited a significant bidirectional causal relationship with OC.

Conclusion: Our study revealed causal relationships of GM and intermediate metabolites with OC/EC, providing new avenues for understanding OC/EC and developing effective treatment strategies.

查看原文本刊更多论文

研究目的该研究旨在利用孟德尔随机分析法（MR）研究肠道微生物群（GM）、卵巢癌（OC）、子宫内膜癌（EC）的因果关系以及潜在的代谢物介导因素：方法：采用双向双样本MR分析和GM对OC/EC的反向MR分析，确定GM对OC/EC的因果效应以及血液代谢物在GM与OC/EC关系中的中介作用，并通过敏感性分析验证结果：结果：我们发现了 6 个与 OC 相关的致病细菌类群，包括极毛杆菌属、志贺氏杆菌属、XIIIAD3011 家族、普雷沃特氏菌属9 和两个未知属。发现克里斯滕森菌科 R.7群、Tyzzerella3和Victivallaceae对OC有保护作用。EC风险的增加与Erysipelotrichia、Erysipelotrichaceae、Erysipelotrichales和FamilyXI呈正相关。Dorea、RuminococcaceaeUCG014和Turisibacter则与癌变风险呈负相关。与基因改造有关的血液代谢物共有 26 种和 19 种，分别与 OC 和 EC 呈显著相关。发现胞嘧啶是与EC和FamilyXI密切相关的中间代谢物。在反向 MR 分析中，FamilyXIIIAD3011 组与 OC 呈显著的双向因果关系：我们的研究揭示了 GM 和中间代谢物与 OC/EC 的因果关系，为了解 OC/EC 和制定有效的治疗策略提供了新的途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Ovarian Research REPRODUCTIVE BIOLOGY-

CiteScore

6.20

自引率

2.50%

发文量

125

审稿时长

>12 weeks

期刊介绍： Journal of Ovarian Research is an open access, peer reviewed, online journal that aims to provide a forum for high-quality basic and clinical research on ovarian function, abnormalities, and cancer. The journal focuses on research that provides new insights into ovarian functions as well as prevention and treatment of diseases afflicting the organ. Topical areas include, but are not restricted to: Ovary development, hormone secretion and regulation Follicle growth and ovulation Infertility and Polycystic ovarian syndrome Regulation of pituitary and other biological functions by ovarian hormones Ovarian cancer, its prevention, diagnosis and treatment Drug development and screening Role of stem cells in ovary development and function.