Causal relationships between gut microbiota and polycystic ovarian syndrome: A bidirectional Mendelian randomization study

Abstract Introduction Previous studies have established a link between gut microbiota and polycystic ovary syndrome (PCOS), but little is known about their precise causal relationship. Therefore, this study aims to explore whether there are precise causal relationships between gut microbiota and PCO...

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Main Authors: Ruo‐Lin Mao, Xiang‐Fei Wang, Jue‐Pu Zhou, Meng Wang, Rui Long, Lei Jin, Li‐Xia Zhu
Format: Article
Language:English
Published: Wiley 2024-11-01
Series:Acta Obstetricia et Gynecologica Scandinavica
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Online Access:https://doi.org/10.1111/aogs.14957
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author Ruo‐Lin Mao
Xiang‐Fei Wang
Jue‐Pu Zhou
Meng Wang
Rui Long
Lei Jin
Li‐Xia Zhu
author_facet Ruo‐Lin Mao
Xiang‐Fei Wang
Jue‐Pu Zhou
Meng Wang
Rui Long
Lei Jin
Li‐Xia Zhu
author_sort Ruo‐Lin Mao
collection DOAJ
description Abstract Introduction Previous studies have established a link between gut microbiota and polycystic ovary syndrome (PCOS), but little is known about their precise causal relationship. Therefore, this study aims to explore whether there are precise causal relationships between gut microbiota and PCOS. Material and Methods We performed a bidirectional two‐sample Mendelian randomization (MR) analysis. Datasets were from the largest published meta‐analysis on gut microbiota composition and the FinnGen cohort of the IEU Open Genome‐Wide Association Study Project database. Inverse variance weighted (IVW), MR‐Egger, constrained maximum likelihood‐based Mendelian randomization, weighted median, weighted mode, and simple mode were used. Cochran's Q and MR‐Egger intercept tests were employed to measure the heterogeneity. Results A total of 211 gut microbiota taxa were identified in MR analysis. Nine taxa of bacteria, including Alphaproteobacteria (0.55, 0.30–0.99, p = 0.04), Bacilli (1.76, 1.07–2.91, p = 0.03), Bilophila (0.42, 0.23–0.77, p < 0.01), Blautia (0.16, 0.03–0.79, p = 0.02), Burkholderiales (2.37, 1.22–4.62, p = 0.01), Candidatus Soleaferrea (0.65, 0.43–0.98, p = 0.04), Cyanobacteria (0.51, 0.31–0.83, p = 0.01), Holdemania (0.53, 0.35–0.81, p < 0.01), and Lachnospiraceae (1.86, 1.04–3.35, p = 0.03), were found to be associated with PCOS in the above MR methods included at least IVW method. Cochran's Q statistics and MR‐Egger intercept test suggested no significant heterogeneity. In addition, 69 taxa were shown significant for at least the IVW method in reverse MR analysis, of these, 25 had a positive correlation, and 37 had a negative correlation. Additionally, Alphaproteobacteria and Lachnospiraceae (0.95, 0.91–0.98, p < 0.01; 0.97, 0.94–0.99, p = 0.02, respectively) were shown a bidirected causally association with PCOS. Conclusions Our study provides evidence of the bidirectional causal association between gut microbiota and PCOS from a genetic perspective.
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spelling doaj-art-651c9b3e245b4077a1835b7cdf1d30772025-08-20T02:09:27ZengWileyActa Obstetricia et Gynecologica Scandinavica0001-63491600-04122024-11-01103112232224110.1111/aogs.14957Causal relationships between gut microbiota and polycystic ovarian syndrome: A bidirectional Mendelian randomization studyRuo‐Lin Mao0Xiang‐Fei Wang1Jue‐Pu Zhou2Meng Wang3Rui Long4Lei Jin5Li‐Xia Zhu6Reproductive Medicine Center, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaReproductive Medicine Center, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaReproductive Medicine Center, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaReproductive Medicine Center, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaReproductive Medicine Center, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaReproductive Medicine Center, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaReproductive Medicine Center, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaAbstract Introduction Previous studies have established a link between gut microbiota and polycystic ovary syndrome (PCOS), but little is known about their precise causal relationship. Therefore, this study aims to explore whether there are precise causal relationships between gut microbiota and PCOS. Material and Methods We performed a bidirectional two‐sample Mendelian randomization (MR) analysis. Datasets were from the largest published meta‐analysis on gut microbiota composition and the FinnGen cohort of the IEU Open Genome‐Wide Association Study Project database. Inverse variance weighted (IVW), MR‐Egger, constrained maximum likelihood‐based Mendelian randomization, weighted median, weighted mode, and simple mode were used. Cochran's Q and MR‐Egger intercept tests were employed to measure the heterogeneity. Results A total of 211 gut microbiota taxa were identified in MR analysis. Nine taxa of bacteria, including Alphaproteobacteria (0.55, 0.30–0.99, p = 0.04), Bacilli (1.76, 1.07–2.91, p = 0.03), Bilophila (0.42, 0.23–0.77, p < 0.01), Blautia (0.16, 0.03–0.79, p = 0.02), Burkholderiales (2.37, 1.22–4.62, p = 0.01), Candidatus Soleaferrea (0.65, 0.43–0.98, p = 0.04), Cyanobacteria (0.51, 0.31–0.83, p = 0.01), Holdemania (0.53, 0.35–0.81, p < 0.01), and Lachnospiraceae (1.86, 1.04–3.35, p = 0.03), were found to be associated with PCOS in the above MR methods included at least IVW method. Cochran's Q statistics and MR‐Egger intercept test suggested no significant heterogeneity. In addition, 69 taxa were shown significant for at least the IVW method in reverse MR analysis, of these, 25 had a positive correlation, and 37 had a negative correlation. Additionally, Alphaproteobacteria and Lachnospiraceae (0.95, 0.91–0.98, p < 0.01; 0.97, 0.94–0.99, p = 0.02, respectively) were shown a bidirected causally association with PCOS. Conclusions Our study provides evidence of the bidirectional causal association between gut microbiota and PCOS from a genetic perspective.https://doi.org/10.1111/aogs.14957causal inferencegut microbiotaGWASMendelian randomizationpolycystic ovary syndrome
spellingShingle Ruo‐Lin Mao
Xiang‐Fei Wang
Jue‐Pu Zhou
Meng Wang
Rui Long
Lei Jin
Li‐Xia Zhu
Causal relationships between gut microbiota and polycystic ovarian syndrome: A bidirectional Mendelian randomization study
Acta Obstetricia et Gynecologica Scandinavica
causal inference
gut microbiota
GWAS
Mendelian randomization
polycystic ovary syndrome
title Causal relationships between gut microbiota and polycystic ovarian syndrome: A bidirectional Mendelian randomization study
title_full Causal relationships between gut microbiota and polycystic ovarian syndrome: A bidirectional Mendelian randomization study
title_fullStr Causal relationships between gut microbiota and polycystic ovarian syndrome: A bidirectional Mendelian randomization study
title_full_unstemmed Causal relationships between gut microbiota and polycystic ovarian syndrome: A bidirectional Mendelian randomization study
title_short Causal relationships between gut microbiota and polycystic ovarian syndrome: A bidirectional Mendelian randomization study
title_sort causal relationships between gut microbiota and polycystic ovarian syndrome a bidirectional mendelian randomization study
topic causal inference
gut microbiota
GWAS
Mendelian randomization
polycystic ovary syndrome
url https://doi.org/10.1111/aogs.14957
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