Association between gut microbiota and endometriosis: a two-sample Mendelian randomization study

Abstract

BackgroundRecent studies have shown that an imbalance in gut microbiota (GM) may not always be associated with endometriosis (EMS). To investigate this further, we conducted a two-sample Mendelian randomization study.MethodsMR analysis was performed on genome-wide association study (GWAS) summary statistics of GM and EMS. Specifically, the MiBioGen microbiota GWAS (N = 18,340) was used as exposure. The FinnGen study GWAS (8,288 EMS cases and 68,969 controls) was used as outcome. We primarily used the inverse variance weighted (IVW) method to analyze the correlation and conducted a sensitivity analysis to verify its reliability.Results(1) MR analysis: The results of the IVW method confirmed that a total of 8 GM taxa were related to the risk of EMS. Class-Melainabacteria (p = 0.036), family-Ruminococcaceae (p = 0.037), and genus-Eubacteriumruminantium (p = 0.015) had a protective effect on EMS, whereas order-Bacillales (p = 0.046), family-Prevotellaceae (p = 0.027), genus-Anaerotruncus (p = 0.025), genus-Olsenella (p = 0.036) and genus-RuminococcaceaeUCG002 (p = 0.035) could increase the risk of EMS. (2) Sensitivity analysis: Cochrane’s Q test (p > 0.05), MR-Egger intercept method (p > 0.05), and leave-one-out method confirmed the robustness of MR results.ConclusionThis study performed a MR analysis on two large national databases and identified the association between 8 GM taxa and EMS. These taxa could potentially be utilized for indirectly diagnosing EMS and could lead to novel perspectives in research regarding the pathogenesis, diagnosis, and treatment of EMS.

Unraveling the relationship between gut microbiota and site-specific endometriosis: a Mendelian randomization analysis

“…The first two exert protective effects against the fallopian tube, vagina, and rectovaginal septum endometriosis, as well as endometriosis-related infertility, whereas the third poses a risk for intestinal endometriosis. Past research has established a causal link between Ruminococcaceae and endometriosis ( Ji et al, 2023 ). Ruminococcaceae is known primarily for producing acetic acid ( Chassard and Bernalier-Donadille, 2006 ), and some members follow a succinate pathway with succinate as the end product instead of propionate ( Louis and Flint, 2017 ).…”

“…Ruminococcaceae is known primarily for producing acetic acid ( Chassard and Bernalier-Donadille, 2006 ), and some members follow a succinate pathway with succinate as the end product instead of propionate ( Louis and Flint, 2017 ). Ji et al (2023) suggested that the divergent abilities of Ruminococcaceae members to produce butyrate might account for the contrasting causal relationships within the Ruminococcaceae family. Further investigation is required to explore these aspects in the future.…”

Role of the gut microbiota in the pathogenesis of endometriosis: a review

“…A two-sample Mendelian randomization (MR) study confirms that a total of 8 gut microbiota taxa are associated with endometriosis, among which the Class-Melainabacteria, family-Ruminococcaceae, and genus-Eubacteriumruminantium had a protective effect on endometriosis, while order-Bacillales, family-Prevotellaceae, genus-Anaerotruncus, genus-Olsenella, and genus-RuminococcaceaeUCG002 may increase the risk of endometriosis. These taxa may be used for indirect diagnosis of endometriosis (Ji et al, 2023). More and more evidence observed that gut microbiota may affect endometriosis through gut microbiota-derived metabolites, which provides a new direction for early diagnosis of Endometriosis.…”