THE ROLE OF MICROBIOME ALTERATIONS IN THE PATHOGENESIS AND MANAGEMENT OF ENDOMETRIOSIS

Endometriosis, Microbiome, Dysbiosis, Estrogen

The condition endometriosis is a chronic gynecological disorder characterized by ectopic endometrial tissue, causing pelvic pain and infertility. Recent research suggests that changes in the gut, vaginal, and endometrial microbiomes may impact gut estrogen processing, inflammation, and immune modulation, which in turn may influence the development of the disorder and the diverse treatment outcomes.

To explore the role of microbiome alterations in the pathogenesis of endometriosis and evaluate their potential therapeutic and management implications. Methodology: This cross-sectional study involved analyzing cases of endometriosis diagnosed during laparoscopic surgeries performed on reproductive-age women at the Obstetrics and Gynecology department of Qazi Hussain Ahmed Medical Complex, Nowshera, from October 25, 2024, to 25 March 2025. 16S rRNA sequencing was performed on samples obtained from the endometrium, feces, and vagina of women, as well as on the microbial communities of these women, which were compared to those of healthy control women. Demographic and clinical symptomatology, as well as biochemical variables, were documented. For the statistical analysis, the Student t-test and p-statistic were used.

In this research, we analyzed a cohort of 150 patients with surgically treated endometriosis. The mean age of these patients was 31.8 years, with a standard deviation of 6.2 years. In some comparisons, patients demonstrated a reduced presence of Lactobacillus species within their vaginal and endometrial microbiomes, and, relative to 150 healthy controls, an increased presence of vaginal and endometrial pathogens, primarily Gardnerella and Streptococcus. Additionally, the intestinal microbiome underwent an overall loss of diversity, changes in astrobleme composition, and an increase in the concentration of estrogen in systemic circulation. The differences between the studied groups were statistically significant (p < 0.01). The presence of dysbiosis of the gut microbiome was associated with a greater prevalence of chronic pelvic pain.

Alterations in the microbiome may contribute to the development of endometriosis and subsequently influence its pathogenesis through alterations in estrogen metabolism, immune response, and inflammation. Probiotic, dietary, and novel microbiome-centric approaches may serve as adjuncts in managing the disease. There is a need for longitudinal studies to assess the causation and efficacy of these treatments.

2. Jiang I, Yong PJ, Allaire C, Bedaiwy MA. Intricate Connections between the Microbiota and Endometriosis. International journal of molecular sciences. 2021;22(11). 3. Pai AH, Wang YW, Lu PC, Wu HM, Xu JL, Huang HY. Gut Microbiome-Estrobolome Profile in Reproductive-Age Women with Endometriosis. International journal of molecular sciences. 2023;24(22). 4. Pérez-Prieto I, Vargas E, Salas-Espejo E, Lüll K, Canha-Gouveia A, Pérez LA, et al. Gut microbiome in endometriosis: a cohort study on 1000 individuals. BMC medicine. 2024;22(1):294. 5. Salliss ME, Farland LV, Mahnert ND, Herbst-Kralovetz MM. The role of gut and genital microbiota and the estrobolome in endometriosis, infertility and chronic pelvic pain. Human reproduction update. 2021;28(1):92-131. 6. Sanabani SS. The Role of the Microbiome in Endometriosis. Reproductive sciences (Thousand Oaks, Calif). 2025. 7. Sobstyl A, Chałupnik A, Mertowska P, Grywalska E. How Do Microorganisms Influence the Development of Endometriosis? Participation of Genital, Intestinal and Oral Microbiota in Metabolic Regulation and Immunopathogenesis of Endometriosis. International journal of molecular sciences. 2023;24(13). 8. Wang MY, Sang LX, Sun SY. Gut microbiota and female health. World journal of gastroenterology. 2024;30(12):1655-62. 9. Xholli A, Cremonini F, Perugi I, Londero AP, Cagnacci A. Gut Microbiota and Endometriosis: Exploring the Relationship and Therapeutic Implications. Pharmaceuticals (Basel, Switzerland). 2023;16(12). 10. 10. Zizolfi B, Foreste V, Gallo A, Martone S, Giampaolino P, Di Spiezio Sardo A. Endometriosis and dysbiosis: State of art. Frontiers in endocrinology. 2023;14:1140774. 11. Alghetaa H, Mohammed A, Singh NP, Bloomquist RF, Chatzistamou I, Nagarkatti M, et al. Estrobolome dysregulation is associated with altered immunometabolism in a mouse model of endometriosis. Frontiers in endocrinology. 2023;14:1261781. 12. Baușic AIG, Scurtu F, Manu A, Matasariu DR, Brătilă E. Gut Microbiota Dysbiosis in Endometriosis: A Potential Link to Inflammation and Disease Progression. International journal of molecular sciences. 2025;26(11). 13. Cao W, Fu X, Zhou J, Qi Q, Ye F, Li L, et al. The effect of the female genital tract and gut microbiome on reproductive dysfunction. Bioscience trends. 2024;17(6):458-74. 14. Datkhayeva Z, Iskakova A, Mireeva A, Seitaliyeva A, Skakova R, Kulniyazova G, et al. The Multifactorial Pathogenesis of Endometriosis: A Narrative Review Integrating Hormonal, Immune, and Microbiome Aspects. Medicina (Kaunas, Lithuania). 2025;61(5). 15. Hamamah S, Barry F, Vannier S, Anahory T, Haahtela T, Antó JM, et al. Infertility, IL-17, IL-33 and Microbiome Cross-Talk: The Extended ARIA-MeDALL Hypothesis. International journal of molecular sciences. 2024;25(22). 16. Kalopedis EA, Zorgani A, Zinovkin DA, Barri M, Wood CD, Pranjol MZI. Leveraging the role of the microbiome in endometriosis: novel non-invasive and therapeutic approaches. Frontiers in immunology. 2025;16:1631522. 17. Le N, Cregger M, Brown V, Loret de Mola J, Bremer P, Nguyen L, et al. Association of microbial dynamics with urinary estrogens and estrogen metabolites in patients with endometriosis. PloS one. 2021;16(12):e0261362. 18. Li Z, Yin Z, Chen W, Wang Z. Impact of Gut and Reproductive Tract Microbiota on Estrogen Metabolism in Endometriosis. American journal of reproductive immunology (New York, NY : 1989). 2025;93(6):e70109. 19. Moustakli E, Zagorianakou N, Makrydimas S, Oikonomou ED, Miltiadous A, Makrydimas G. The Gut-Endometriosis Axis: Genetic Mechanisms and Public Health Implications. Genes. 2025;16(8). 20. Toffoli M, Campisciano G, Santin A, Pegoraro S, Zito G, Spedicati B, et al. A possible association between low MBL/lectin pathway functionality and microbiota dysbiosis in endometriosis patients. Life sciences. 2025;364:123427.