Causal association between gut microbiota and endometrial cancer in European and East Asian populations: a two-sample Mendelian randomization study

Abstract Background Endometrial cancer (EC) is a significant global health concern. While observational epidemiological studies suggest a potential link between gut microbiota dysbiosis and the development of EC, the direction and causality of this association remain uncertain. Methods We performed...

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Main Authors: Jiaqi Chen, Haiqing Li, Xinrui Long, Hao Tong, Xin Xin, Han Zhang, Yeyao Li, Ping Liu, Xiaolin He, Zhuoyuan Chen
Format: Article
Language:English
Published: BMC 2025-06-01
Series:BMC Women's Health
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Online Access:https://doi.org/10.1186/s12905-025-03789-x
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author Jiaqi Chen
Haiqing Li
Xinrui Long
Hao Tong
Xin Xin
Han Zhang
Yeyao Li
Ping Liu
Xiaolin He
Zhuoyuan Chen
author_facet Jiaqi Chen
Haiqing Li
Xinrui Long
Hao Tong
Xin Xin
Han Zhang
Yeyao Li
Ping Liu
Xiaolin He
Zhuoyuan Chen
author_sort Jiaqi Chen
collection DOAJ
description Abstract Background Endometrial cancer (EC) is a significant global health concern. While observational epidemiological studies suggest a potential link between gut microbiota dysbiosis and the development of EC, the direction and causality of this association remain uncertain. Methods We performed Mendelian randomization (MR) analysis to investigate the causal relationship between gut microbiota and EC. Exposure data were obtained from the MiBioGen study consortium (N = 18,340), and outcome data were sourced from the IEU OpenGWAS database, specifically datasets “ebi-a-GCST006464” (N = 121,885) and “bbj-a-113” (N = 90,730). The inverse variance-weighted(IVW) method was applied to evaluate the association between gut microbiota composition and EC risk. Sensitivity analyses were conducted to ensure the robustness of the findings. Results Our study identified several microbial taxa linked to EC risk. In Europeans, genera such as Marvinbryantia, RuminococcaceaeUCG014, and Dorea exhibited protective effects, while family Erysipelotrichaceae (OR:1.224) and FamilyXI (OR:1.090) were significantly correlated with high EC risk. In East Asians, genera Lachnospira (OR:3.561) and family Bifidobacteriaceae (OR:1.715) were found associated with EC risk. Genera Lachnoclostridium and ErysipelotrichaceaeUCG003, family Coriobacteriaceae positively served as protective factors. Sensitivity analyses confirmed the reliability of our results, and there was no evidence of pleiotropy or heterogeneity. Our analysis identified several microbial taxa associated with EC risk. In Europeans, genera such as Marvinbryantia, Ruminococcaceae UCG014, and Dorea demonstrated protective effects, while the families Erysipelotrichaceae (OR: 1.224) and FamilyXI (OR: 1.090) were significantly associated with increased EC risk. In East Asians, the genus Lachnospira (OR: 3.561) and the family Bifidobacteriaceae (OR: 1.715) were linked to higher EC risk, whereas the genera Lachnoclostridium and Erysipelotrichaceae UCG003 and the family Coriobacteriaceae were identified as protective factors. Sensitivity analyses confirmed the reliability of these results, with no evidence of pleiotropy or heterogeneity. Conclusion This study highlights a relationship between gut microbiota and EC, emphasizing the potential of gut microbiota as therapeutic targets and biomarkers for assessing EC prognosis and treatment efficacy. These findings provide novel insights into the role of gut microbiota in the development and progression of EC.
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spelling doaj-art-dc740daa47d3487cafdc5b9b2c454dc72025-08-20T02:05:39ZengBMCBMC Women's Health1472-68742025-06-0125111110.1186/s12905-025-03789-xCausal association between gut microbiota and endometrial cancer in European and East Asian populations: a two-sample Mendelian randomization studyJiaqi Chen0Haiqing Li1Xinrui Long2Hao Tong3Xin Xin4Han Zhang5Yeyao Li6Ping Liu7Xiaolin He8Zhuoyuan Chen9Key Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Yan’an Hospital Affiliated to, Kunming Medical UniversityKey Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Yan’an Hospital Affiliated to, Kunming Medical UniversityXiangya School of Medicine, Central South UniversityDepartment of Spine Surgery, the Second Xiangya Hospital of Central South UniversityDepartment of Orthopedics of Yan’an Hospital, Affiliated to Kunming Medical UniversityKey Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Yan’an Hospital Affiliated to, Kunming Medical UniversityKey Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Yan’an Hospital Affiliated to, Kunming Medical UniversityKey Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Yan’an Hospital Affiliated to, Kunming Medical UniversityKey Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Yan’an Hospital Affiliated to, Kunming Medical UniversityKey Laboratory of Tumor Immunological Prevention and Treatment of Yunnan Province, Yan’an Hospital Affiliated to, Kunming Medical UniversityAbstract Background Endometrial cancer (EC) is a significant global health concern. While observational epidemiological studies suggest a potential link between gut microbiota dysbiosis and the development of EC, the direction and causality of this association remain uncertain. Methods We performed Mendelian randomization (MR) analysis to investigate the causal relationship between gut microbiota and EC. Exposure data were obtained from the MiBioGen study consortium (N = 18,340), and outcome data were sourced from the IEU OpenGWAS database, specifically datasets “ebi-a-GCST006464” (N = 121,885) and “bbj-a-113” (N = 90,730). The inverse variance-weighted(IVW) method was applied to evaluate the association between gut microbiota composition and EC risk. Sensitivity analyses were conducted to ensure the robustness of the findings. Results Our study identified several microbial taxa linked to EC risk. In Europeans, genera such as Marvinbryantia, RuminococcaceaeUCG014, and Dorea exhibited protective effects, while family Erysipelotrichaceae (OR:1.224) and FamilyXI (OR:1.090) were significantly correlated with high EC risk. In East Asians, genera Lachnospira (OR:3.561) and family Bifidobacteriaceae (OR:1.715) were found associated with EC risk. Genera Lachnoclostridium and ErysipelotrichaceaeUCG003, family Coriobacteriaceae positively served as protective factors. Sensitivity analyses confirmed the reliability of our results, and there was no evidence of pleiotropy or heterogeneity. Our analysis identified several microbial taxa associated with EC risk. In Europeans, genera such as Marvinbryantia, Ruminococcaceae UCG014, and Dorea demonstrated protective effects, while the families Erysipelotrichaceae (OR: 1.224) and FamilyXI (OR: 1.090) were significantly associated with increased EC risk. In East Asians, the genus Lachnospira (OR: 3.561) and the family Bifidobacteriaceae (OR: 1.715) were linked to higher EC risk, whereas the genera Lachnoclostridium and Erysipelotrichaceae UCG003 and the family Coriobacteriaceae were identified as protective factors. Sensitivity analyses confirmed the reliability of these results, with no evidence of pleiotropy or heterogeneity. Conclusion This study highlights a relationship between gut microbiota and EC, emphasizing the potential of gut microbiota as therapeutic targets and biomarkers for assessing EC prognosis and treatment efficacy. These findings provide novel insights into the role of gut microbiota in the development and progression of EC.https://doi.org/10.1186/s12905-025-03789-xGut microbiotaEndometrial cancerMendelian randomizationCausal relationshipInstrumental variables
spellingShingle Jiaqi Chen
Haiqing Li
Xinrui Long
Hao Tong
Xin Xin
Han Zhang
Yeyao Li
Ping Liu
Xiaolin He
Zhuoyuan Chen
Causal association between gut microbiota and endometrial cancer in European and East Asian populations: a two-sample Mendelian randomization study
BMC Women's Health
Gut microbiota
Endometrial cancer
Mendelian randomization
Causal relationship
Instrumental variables
title Causal association between gut microbiota and endometrial cancer in European and East Asian populations: a two-sample Mendelian randomization study
title_full Causal association between gut microbiota and endometrial cancer in European and East Asian populations: a two-sample Mendelian randomization study
title_fullStr Causal association between gut microbiota and endometrial cancer in European and East Asian populations: a two-sample Mendelian randomization study
title_full_unstemmed Causal association between gut microbiota and endometrial cancer in European and East Asian populations: a two-sample Mendelian randomization study
title_short Causal association between gut microbiota and endometrial cancer in European and East Asian populations: a two-sample Mendelian randomization study
title_sort causal association between gut microbiota and endometrial cancer in european and east asian populations a two sample mendelian randomization study
topic Gut microbiota
Endometrial cancer
Mendelian randomization
Causal relationship
Instrumental variables
url https://doi.org/10.1186/s12905-025-03789-x
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