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

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...

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Main Authors: Jinyan Chen, Xuejun Chen, Jiong Ma
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Journal of Ovarian Research
Subjects:
Online Access:https://doi.org/10.1186/s13048-025-01630-5
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author Jinyan Chen
Xuejun Chen
Jiong Ma
author_facet Jinyan Chen
Xuejun Chen
Jiong Ma
author_sort Jinyan Chen
collection DOAJ
description 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.
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spelling doaj-art-dc433a609a1643b39a2ce5a2a68d55e32025-08-20T03:01:34ZengBMCJournal of Ovarian Research1757-22152025-03-0118111710.1186/s13048-025-01630-5Causal relationships of gut microbiota and blood metabolites with ovarian cancer and endometrial cancer: a Mendelian randomization studyJinyan Chen0Xuejun Chen1Jiong Ma2Department of Gynecology, School of Medicine, The Second Affiliated Hospital of Zhejiang UniversityDepartment of Gynecology, School of Medicine, The Second Affiliated Hospital of Zhejiang UniversityDepartment of Gynecology, School of Medicine, The Second Affiliated Hospital of Zhejiang UniversityAbstract 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.https://doi.org/10.1186/s13048-025-01630-5Mendelian randomizationMetabolitesGut microbiotaOvarian cancerEndometrial cancer
spellingShingle Jinyan Chen
Xuejun Chen
Jiong Ma
Causal relationships of gut microbiota and blood metabolites with ovarian cancer and endometrial cancer: a Mendelian randomization study
Journal of Ovarian Research
Mendelian randomization
Metabolites
Gut microbiota
Ovarian cancer
Endometrial cancer
title Causal relationships of gut microbiota and blood metabolites with ovarian cancer and endometrial cancer: a Mendelian randomization study
title_full Causal relationships of gut microbiota and blood metabolites with ovarian cancer and endometrial cancer: a Mendelian randomization study
title_fullStr Causal relationships of gut microbiota and blood metabolites with ovarian cancer and endometrial cancer: a Mendelian randomization study
title_full_unstemmed Causal relationships of gut microbiota and blood metabolites with ovarian cancer and endometrial cancer: a Mendelian randomization study
title_short Causal relationships of gut microbiota and blood metabolites with ovarian cancer and endometrial cancer: a Mendelian randomization study
title_sort causal relationships of gut microbiota and blood metabolites with ovarian cancer and endometrial cancer a mendelian randomization study
topic Mendelian randomization
Metabolites
Gut microbiota
Ovarian cancer
Endometrial cancer
url https://doi.org/10.1186/s13048-025-01630-5
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AT jiongma causalrelationshipsofgutmicrobiotaandbloodmetaboliteswithovariancancerandendometrialcanceramendelianrandomizationstudy