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Updated: Jul 24, 2025
Characterization and Functional Prediction of Bacteria in Ovarian Tissues
Published on: October 23, 2021
Association between gut microbiota and primary ovarian insufficiency: a bidirectional two-sample Mendelian
Jiahui Wang1, Rong Luo2, Xia Zhao1,2
1School of Medicine, Southeast University, Nanjing, China.
Background:
Recent studies have indicated a potential correlation between intestinal bacteria and primary ovarian insufficiency (POI). However, the causal relationship between the gut microbiota (GM) and POI remains unclear.
Methods:
A bidirectional two-sample Mendelian randomization (MR) study was conducted to investigate the relationship between the GM and POI. Data on the GM were based on the MiBioGen consortium's summary statistics from the most comprehensive genome-wide association study meta-analysis to date (n=13,266), and POI data were obtained from the R8 release of the FinnGen consortium, containing a total of 424 cases and 181,796 controls. A variety of analytical methods, including inverse variance weighting, maximum likelihood, MR-Egger, weighted median, and constrained maximum likelihood and model averaging and Bayesian information criterion, were utilized to explore the connection between the GM and POI. The Cochran's Q statistics were used to evaluate the heterogeneity of instrumental variables. The MR-Egger and MR-pleiotropy residual sum and outlier (PRESSO) methods were used to identify the horizontal pleiotropy of instrumental variables. The MR Steiger test was used to evaluate the strength of causal relationships. A reverse MR study was performed to investigate the causal relationship between POI and the targeted GMs which were indicated to have a causal relationship with POI in the forward MR evaluation.
Results:
The inverse variance weighted analysis indicated that Eubacterium (hallii group) (odds ratio [OR]=0.49, 95% confidence interval [CI]: 0.26-0.9, P=0.022) and Eubacterium (ventriosum group) (OR=0.51, 95% CI: 0.27-0.97, P=0.04) had protective effects on POI, and Intestinibacter (OR=1.82, 95% CI: 1.04-3.2, P=0.037) and Terrisporobacter (OR=2.47, 95% CI: 1.14-5.36, P=0.022) had detrimental effects on POI. Results of the reverse MR analysis indicated that POI had no significant influence on the four GMs. No significant heterogeneity or horizontal pleiotropy was observed in the performance of the instrumental variables.
Conclusion:
This bidirectional two-sample MR study revealed a causal link between Eubacterium (hallii group), Eubacterium (ventriosum group), Intestinibacter, and Terrisporobacter and POI. Additional clinical trials are needed to gain a clearer understanding of the beneficial or detrimental effects of the GMs on POI and their mechanisms of action.
Insights
This study found specific gut bacteria, including Eubacterium species, Intestinibacter, and Terrisporobacter, causally linked to primary ovarian insufficiency (POI). Some bacteria may protect against POI, while others increase risk.
Area of Science:
- Microbiome research
- Reproductive health
- Genetic epidemiology
Background:
- Primary ovarian insufficiency (POI) is a condition affecting women's reproductive health.
- The relationship between gut microbiota (GM) and POI is not fully understood.
- Investigating potential causal links between GM and POI is crucial for understanding disease mechanisms.
Approach:
- A bidirectional two-sample Mendelian randomization (MR) study was employed.
- Utilized large-scale genome-wide association study data for GM and POI.
- Applied various analytical methods to assess causality and identify potential pleiotropy.
Key Points:
- Eubacterium (hallii group) and Eubacterium (ventriosum group) showed a protective association with POI.
- Intestinibacter and Terrisporobacter were associated with an increased risk of POI.
- Reverse MR analysis indicated no significant causal effect of POI on these gut bacteria.
Conclusions:
- Established a causal relationship between specific gut bacteria (Eubacterium species, Intestinibacter, Terrisporobacter) and POI.
- Highlights the potential role of the gut microbiota in the pathogenesis of POI.
- Further clinical research is warranted to elucidate the mechanisms and therapeutic implications.
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