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Updated: Jun 9, 2025
Author Spotlight: Investigating the Mechanisms and Inducing Models of Polycystic Ovary Syndrome
Published on: July 5, 2024
Exploring the causal pathway from gut microbiota to polycystic ovary syndrome: A network Mendelian randomization
Xueyan Gao1, Huijuan Zhao, Qingling Shi
1Department of General Medicine, Geriatric Hospital of Nanjing Medical University, Nanjing, China.
Abstract:
Polycystic ovary syndrome (PCOS) is a complicated endocrine and metabolic syndrome with unclear pathogenesis. The gut microbiota sheds light on the etiology and pathophysiology of PCOS. We used Mendelian randomization (MR) studies to systematically evaluate the pathological mechanism gut microbiota causally associated with PCOS risk. A network MR analysis was performed to estimate the causal effects of gut microbiota and risk factors on PCOS, as well as the mediation effect of risk factors linking gut microbiota to PCOS. The investigation of side effects for the important gut microbiota was subsequently broadened to include phenotypes by performing Phenowide-MR analysis for a range of diseases. Genus Sellimonas id.14369 were causally associated with reduced PCOS risk (odds ratio [OR] = 0.69, 95% confidence interval [CI]: 0.58-0.84, P = 1.22 × 10-4) after multiple testing correction. And Sellimonas retained consistent causal effect estimates after a series of sensitivity analyses. In addition, we observed an indirect effect of Sellimonas on PCOS through body mass index (BMI) using network MR (b = -0.05, 95% CI: -0.09 to -0.01), with a mediated proportion of 12.82% of the total effect. Further, Phenowide-MR analyses showed that the protective effects of Sellimonas on type 2 diabetes and depression (for type 2 diabetes: OR = 0.95, 95% CI: 0.90-0.99, P = .0366; for depression: OR = 0.99, 95% CI: 0.98-1.00, P = .0210). We summarized that the causal path between gut microbiota and type 2 diabetes are also jointly mediated by BMI. Sellimonas may be a protective factor of PCOS, which can affect the occurrence of PCOS through BMI, supporting future studies on the importance of addressing obesity and metabolic issues in preventing and managing PCOS.
Insights
The gut bacterium Sellimonas is linked to a lower risk of Polycystic Ovary Syndrome (PCOS). This protective effect is partly mediated by body mass index (BMI), suggesting a role for metabolic health in PCOS prevention.
Area of Science:
- Endocrinology and Metabolism
- Microbiome Research
- Genetics
Background:
- Polycystic Ovary Syndrome (PCOS) is a complex endocrine and metabolic disorder with poorly understood causes.
- The gut microbiota is increasingly recognized for its role in the etiology and pathophysiology of PCOS.
Purpose of the Study:
- To systematically evaluate the causal relationship between gut microbiota and PCOS risk using Mendelian randomization (MR).
- To investigate the mediating role of risk factors, such as body mass index (BMI), in the gut microbiota-PCOS pathway.
- To explore the broader phenotypic effects of key gut bacteria, including Sellimonas, on other diseases.
Main Methods:
- Network Mendelian randomization (MR) analysis was employed to assess causal effects of gut microbiota on PCOS and mediating factors.
- Phenome-wide MR (Phenowide-MR) was used to examine the association of Sellimonas with various disease phenotypes.
- Sensitivity analyses were conducted to confirm the robustness of the findings.
Main Results:
- The gut bacterium *Genus Sellimonas* was causally associated with a reduced risk of PCOS (OR=0.69, P=1.22×10⁻⁴).
- An indirect protective effect of *Sellimonas* on PCOS was observed, mediated by BMI (b=-0.05, P=0.002), accounting for 12.82% of the total effect.
- *Sellimonas* also showed protective associations with type 2 diabetes and depression, with BMI mediating the link to type 2 diabetes.
Conclusions:
- *Genus Sellimonas* may act as a protective factor against PCOS, potentially through its influence on BMI and metabolic health.
- These findings highlight the importance of gut microbiota in PCOS pathogenesis and suggest that addressing obesity and metabolic dysfunction is crucial for PCOS management.
- The gut microbiota's role in metabolic diseases like PCOS and type 2 diabetes warrants further investigation.
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