Gut and genital microbiota in endometriosis

Chernukha G.E., Pronina V.A., Priputnevich T.V.

Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, Moscow, Russia
Endometriosis is a hormone-dependent disease associated with the development of chronic inflammation. The prevalence of this disease does not tend to decrease. The absence of a unified generally accepted theory on the origin of endometriosis is the basis for continuing investigations aimed at searching for possible mechanisms for the development of the disease in order to improve the principles of diagnosis and therapy of this pathological process. One of the theories of endometriosis is the hypothesis of bacterial infection, in which the bacterial endotoxin lipopolysaccharide is supposed to be a triggering factor for the onset and progression of endometriosis. Current data indicate that changes in the composition of gut microbiota and/or different stages of the female reproductive tract can be used prognostically as a tool for diagnosing the disease, whereas a number of microorganisms can be marker for assessing its form and prevalence. This review considers the present-day ideas on the relationship between the gut and genital microbiotas and endometriosis, on possible mechanisms and diagnostic approaches to this pathological condition.
Conclusion: To study the composition of the microbiota seems to be a fairly new and very promising area from both scientific and practical point of view.


gut microbiota
genital microbiota
16S rRNA gene sequencing


  1. Giudice L.C., Kao L.C. Endometriosis. Lancet. 2004; 364(9447): 1789-99.
  2. Kennedy S., Bergqvist A., Chapron C., D'Hooghe T., Dunselman G., Greb R. et al. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum. Reprod. 2005; 20(10): 2698-2704.
  3. Giudice L.C. Endometriosis. N. Engl. J. Med. 2010; 362(25): 2389-98.
  4. Meuleman C., Vandenabeele B., Fieuws S., Spiessens C., Timmerman D., D’Hooghe T. High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. Fertil. Steril. 2009; 92(1): 68-74. 10.1016/j.fertnstert.2008.04.056.
  5. Fuldeore M.J., Soliman A.M. Prevalence and symptomatic burden of diagnosed endometriosis in the United States: National estimates from a cross-sectional survey of 59,411 women. Gynecol. Obstet. Invest. 2016; 82(5): 453-61.
  6. Fauconnier A., Chapron C., Dubuisson J.-B., Vieira M., Dousset B., Bréart G. Relation between pain symptoms and the anatomic location of deep infiltrating endometriosis. Fertil. Steril. 2002; 78(4): 719-26.
  7. Ballard K., Seaman H., de Vries C., Wright J. Can symptomatology help in the diagnosis of endometriosis? Findings from a national case-control study-Part 1. BJOG. 2008; 115(11): 1382-91.
  8. Maroun P., Cooper M.J.W., Reid G.D., Keirse M.J.N.C. Relevance of gastrointestinal symptoms in endometriosis. Aust. N. Z. J. Obstet. Gynaecol. 2009; 49(4): 411-4.
  9. Vercellini P., Fedele L., Aimi G., Pietropaolo G., Consonni D., Crosignani P.G. Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients. Hum. Reprod. 2006; 22(1): 266-71.
  10. Greene R., Stratton P., Cleary S.D., Ballweg M.L., Sinaii N. Diagnostic experience among 4,334 women reporting surgically diagnosed endometriosis. Fertil. Steril. 2009; 91: 32-9.
  11. Johnson N.P., Hummelshoj L.; World Endometriosis Society Montpellier Consortium. Consensus on current management of endometriosis. Hum. Reprod. 2013; 28(6): 1552-68.
  12. Dunselman G.A., Vermeulen N., Becker C., Calhaz-Jorge C., D'Hooghe T., De Bie B. et al. ESHRE guideline: management of women with endometriosis. Hum. Reprod. 2014; 29(3): 400-12.
  13. Министерство здравоохранения Российской Федерации. Эндометриоз. Клинические рекомендации М.; 2020. [Ministry of Health of the Russian Federation. Endometriosis. Clinical recommendations. M.; 2020. (in Russian)]. Available at:$File/%D0%AD%D0%BD%D0%B4%D0%BE%D0%BC%D0%B5%D1%82%D1%80%D0%B8%D0%BE%D0%B7.pdf
  14. RANZCOG. Australian clinical guideline on the diagnosis and management of endometriosis. 2021. Available at:
  15. Collinet P., Fritel X., Revel-Delhom C., Ballester M., Bolze P.A., Borghese B. et al. Management of endometriosis. CNGOF/HAS clinical practice guidelines – Short version. J. Gynecol. Obstet. Hum. Reprod. 2018; 47(7): 265-74.
  16. ESHRE Endometriosis Guideline Group. ESHRE guideline: endometriosis. Hum. Reprod. Open. 2022; 2022(2): hoac009.
  17. Nirgianakis K., Ma L., McKinnon B., Mueller M.D. Recurrence patterns after surgery in patients with different endometriosis subtypes: A Long-Term Hospital-Based Cohort Study. J. Clin. Med. 2020; 9(2): 496.
  18. Sibiude J., Santulli P., MArcellin L., Borghese B., Dousset B., Chapron C. Association of history of surgery for endometriosis with severity of deeply infiltrating endometriosis. Obstet. Gynecol. 2014; 124(4): 709-17.
  19. Муфтайдинова Ш.К., Файзуллин Л.З., Чупрынин В.Д, Русейкин Н.С., Смольнова Т.Ю., Буралкина Н.А. Клинико-диагностические аспекты глубокого инфильтративного эндометриоза (диагностика, лечение, рецидивы). Гинекология. 2021; 23(4): 307-13. [Muftaidinova Sh.K., Faizullin L.Z., Chuprynin V.D., Ruseikin N.S., Smolnova T.Iu., Buralkina N.A. Clinical and diagnostic aspects of deep infiltrative endometriosis (diagnosis, treatment, reccurence). Gynecology. 2021; 23(4): 307-13. (in Russian)].
  20. Yela D.A., Vitale S.G., Vizotto M.P., Benetti‐Pinto C.L. Risk factors for recurrence of deep infiltrating endometriosis after surgical treatment. J. Obstet. Gynaecol. Res. 2021; 47(8): 2713-9.
  21. Sampson J.A. Peritoneal endometriosis due to premenstrual dissemination of endometrial tissue into the peritoneal cavity. Am. J. Obstet. Gynecol.1927; 14: 422-69.
  22. Chapron C., Bricou A., Chopin N., Borghese B., Dousset B., Vacher-Lavenu M.-C. et al. Deeply infiltrating endometriosis: pathogenetic implications of the anatomical distribution. Eur. J. Obstet. Gynecol. Reprod. Biol. 2006; 21(7): 1839-45.
  23. Bricou A., Batt R. E., Chapron C. Peritoneal fluid flow influences anatomical distribution of endometriotic lesions: why Sampson seems to be right. Eur. J. Obstet. Gynecol. Reprod. Biol. 2008; 138(2): 127-34.
  24. Samani E.N., Mamillapalli R., Li F., Mutlu L., Hufnagel D., Krikun G., Taylor H.S. Micrometastasis of endometriosis to distant organs in a murine model. Oncotarget. 2019; 10(23): 2282-91.
  25. Rei C., Williams T., Feloney M. Endometriosis in a man as a rare source of abdominal pain: A case report and review of the literature. Case Rep. Obstet. Gynecol. 2018; 2018: 2083121.
  26. Schenken R.S., Barbieri R.L., Eckler K. Endometriosis: pathogenesis, clinical features, and diagnosis. UpToDate; 2019.
  27. Koninckx P.R., Ussia A., Adamyan L., Wattiez A., Gomel V., Martin D.C. Pathogenesis of endometriosis: the genetic/epigenetic theory. Fertil. Steril. 2019; 111(2): 327-39.
  28. Koninckx P.R., Fernandes R., Ussia A., Schindler L., Wattiez A., Al-Suwaidi S. et al. Pathogenesis based diagnosis and treatment of endometriosis. Front. Endocrinol. (Lausanne). 2021; 12: 745548.
  29. Defrere S., Gonzalez-Ramos R., Lousse J.C., Colette S., Donnez O., Donnez J., Langendonckt A.V. Insights into iron and nuclear factor-kappa B (NF-kappaB) involvement in chronic inflammatory processes in peritoneal endometriosis. Histol. Histopathol. 2011; 26(8): 1083-92.
  30. Koninckx P.R., Ussia A., Adamian L., Gomel V., Martin D.C. Peritoneal fluid progesterone and progesterone resistance in superficial endometriosis lesions. Hum. Reprod. 2022; 37(2): 203-11.
  31. Batt R.E., Yeh J. Mullerianosis: four developmental (embryonic) mullerian diseases. Reprod. Sci. 2013; 20(9): 1030-7.
  32. Hufnagel D., Li F., Cosar E., Krikun G., Taylor H.S. The role of stem cells in the etiology and pathophysiology of endometriosis. Semin. Reprod. Med. 2015; 33(5): 333-40.
  33. Jerman L.F., Hey-Cunningham A.J. The role of the lymphatic system in endometriosis: a comprehensive review of the literature. Biol. Reprod. 2015; 92(3): 64.
  34. Khan K.N., Kitajima M., Hiraki K., Yamaguchi N., Katamine S., Matsuyama T., Masuzaki H. Escherichia coli contamination of menstrual blood and effect of bacterial endotoxin on endometriosis. Fertil. Steril. 2010; 94(7): 2860-3.e3.
  35. Bailey M.T., Coe C.L. Endometriosis is associated with an altered profile of intestinal microflora in female rhesus monkeys. Hum. Reprod. 2002; 17(7): 1704-8.
  36. Deitch E.A., Ma W.J., Ma L., Berg R., Specian R.D. Endotoxin-induced bacterial translocation: a study of mechanisms. Surgery. 1989; 106(2): 292-300.
  37. Alexander J.W., Boyce S.T., Babcock G.F., Gianotti L., Peck M.D., Dunn D.L., Pyles T., Childress C.P., Ash S.K. The process of microbial translocation. Ann. Surg. 1990; 212(4): 496-511.
  38. Neish A.S. Microbes in gastrointestinal health and disease. Gastroenterology. 2009; 136(1): 65-80.
  39. Flint H.J., Scott K.P., Duncan S.H., Louis P., Forano E. Microbial degradation of complex carbohydrates in the gut. Gut Microbes. 2012; 3(4): 289-306.
  40. LeBlanc J.G., Milani C., de Giori G.S., Sesma F., van Sinderen D., Ventura M. Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr. Opin. Biotechnol. 2013; 24(2): 160-8.
  41. Koh A., De Vadder F., Kovatcheva-Datchary P., Bäckhed F. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell. 2016; 165(6): 1332-45.
  42. Raftogianis R., Creveling C., Weinshilboum R., Weisz J. Estrogen metabolism by conjugation. J. Natl. Cancer Inst. Monogr. 2000; (27): 113-24.
  43. Eriksson H., Gustafsson J.A., Sjovall J. Steroids in germfree and conventional rats. Free steroids in faeces from conventional rats. Eur. J. Biochem. 1969; 9(2): 286-90.
  44. Plottel C.S., Blaser M.J. Microbiome and malignancy. Cell Host Microbe. 2011; 10(4): 324-35.
  45. Kwa M., Plottel C.S., Blaser M.J., Adams S. The intestinal microbiome and estrogen receptor-positive female breast cancer. J. Natl. Cancer Inst. 2016; 108(8): djw02.
  46. Baker J.M., Al-Nakkash L., Herbst-Kralovetz M.M. Estrogen–gut microbiome axis: physiological and clinical implications. Maturitas. 2017; 103: 45-53.
  47. Ata B., Yildiz S., Turkgeldi E., Brocal V.P., Dinleyici E.C., Moya A., Urman B. The Endobiota Study: Comparison of vaginal, cervical and gut microbiota between women with stage 3/4 endometriosis and healthy controls. Sci. Rep. 2019; 9(1): 2204.
  48. Yuan M., Li D., Zhang Z., Sun H., An M., Wang G. Endometriosis induces gut microbiota alterations in mice. Hum. Reprod. 2018; 33(4): 607-16.
  49. Svensson A., Brunkwall L., Roth B., Orho-Melander M., Ohlsson, B. Associations between endometriosis and gut microbiota. Reprod. Sci. 2021; 28(8): 2367-77.
  50. Shan J., Ni Z., Cheng W., Zhou L., Zhai D., Sun S., Yu, C. Gut microbiota imbalance and its correlations with hormone and inflammatory factors in patients with stage 3/4 endometriosis. Arch. Gynecol. Obstet. 2021; 304(5): 1363-73.
  51. Chen C., Song X., Wei W., Zhong H., Dai J., Lan Z. et al. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat. Commun. 2017; 8(1): 875.
  52. Кебурия Л.К., Смольникова В.Ю., Припутневич Т.В. Муравьева В.В. Микробиота полости матки и ее влияние на репродуктивные исходы. Акушерство и гинекология. 2019; 2: 22-7. [Keburia L.K., Smolnikova V.Yu., Priputnevich T.V., Muravyeva V.V. Uterine microbiota and its effect on reproductive outcomes. Obstetrics and Gynecology. 2019; 2: 22-7. (in Russian)].
  53. Кебурия Л.К., Смольникова В.Ю., Припутневич Т.В. Муравьева В.В., Трофимов Д.Ю., Шубина Е.C., Кочеткова Т.О. Микробиота полости матки и неудачи имплантации. Есть ли связь? Акушерство и гинекология. 2021; 7: 133-43. [Keburiya L.K., Smol’nikova V.Yu., Priputnevich T.V., Murav’eva V.V., Trofimov D.Yu., Shubina E.S., Kochetkova T.O. Uterine microbiota and implantation failure: is there a link? Obstetrics and Gynecology. 2021; 7: 133-43. (in Russian)].
  54. Huang L., Liu B., Liu Z., Feng W., Liu M., Wang Y. et al. Gut microbiota exceeds cervical microbiota for early diagnosis of ndometriosis. Front. Cell. Infect. Microbiol. 2021; 11: 788836.
  55. Blackburn S.C., Stanton M.P. Anatomy and physiology of the peritoneum. Semin. Pediatr. Surg. 2014; 23(6): 326-30.
  56. Capobianco A., Cottone L., Monno A., Manfredi A.A., Rovere-Querini P. The peritoneum: healing, immunity, and diseases. J. Pathol. 2017; 243(2): 137-47.
  57. Yuan W., Wu Y., Chai X., Wu X. The colonized microbiota composition in the peritoneal fluid in women with endometriosis. Arch. Gynecol. Obstet. 2022; 305(6): 1573-80.
  58. Chang C.Y., Chiang A.J., Lai M.T., Yan M.J., Tseng C.C., Lo L.C. et al. A more diverse cervical microbiome associates with better clinical outcomes in patients with endometriosis: A pilot study. Biomedicines. 2022; 10(1): 174.
  59. Akiyama K., Nishioka K., Khan K. N., Tanaka Y., Mori T., Nakaya T., Kitawaki J. Molecular detection of microbial colonization in cervical mucus of women with and without endometriosis. Am. J. Reprod. Immunol. 2019; 82(2): e13147.
  60. Walther-António M.R.S., Chen J., Multinu F., Hokenstad A., Distad T.J., Cheek E.H. et al. Potential contribution of the uterine microbiome in the development of endometrial cancer. Genome Med. 2016; 8: 122.
  61. Jin M., Kalainy S., Baskota N., Chiang D., Deehan E.C., McDougall C. et al. Faecal microbiota from patients with cirrhosis has a low capacity to ferment non-digestible carbohydrates into short-chain fatty acids. Liver Int. 2019; 39(8): 1437-47.
  62. Uduwela D.R., Pabis A., Stevenson B.J., Kamerlin S.C.L., McLeod M.D. Enhancing the steroid sulfatase activity of the arylsulfatase from pseudomonas aeruginosa. ACS Catalysis. 2018; 8: 8902-14.
  63. Huhtinen K., Desai R., Ståhle M., Salminen A., Handelsman D.J., Perheentupa A., Poutanen M. Endometrial and endometriotic concentrations of estrone and estradiol are determined by local metabolism rather than circulating levels. J. Clin. Endocrinol. Metab. 2012; 97(11): 4228-35.
  64. Lee S.R., Lee J.C., Kim S.H., Oh Y.S., Chae H.D., Seo H., Kang C.S., Shin T.S. Altered composition of microbiota in women with ovarian endometrioma: microbiome analyses of extracellular vesicles in the peritoneal fluid. Int. J. Mol. Sci. 2021; 22(9): 4608.
  65. Perrotta A.R., Borrelli G.M., Martins C.O., Kallas E.G., Sanabani S.S., Griffith L.G. et al. The vaginal microbiome as a tool to predict rASRM stage of disease in endometriosis: A pilot study. Reprod. Sci. 2020; 27(4): 1064-73.

Received 11.04.2022

Accepted 10.06.2022

About the Authors

Galina E. Chernukha, Dr. Med. Sci., Professor, Chief Researcher, obstetrician-gynecologist at the Department of Gynecological Endocrinology, Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russian Federation, +7(985)999-60-00,,
117997, Russia, Moscow, Ac. Oparin str., 4.
Veronika A. Pronina, obstetrician-gynecologist, PhD student, Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology,
Ministry of Health of Russian Federation, +7(916)025-86-26,,, 117997, Russia, Moscow, Ac. Oparin str., 4.
Tatiana V. Priputnevich, Dr. Med. Sci., Associate Professor, Director of the Institute of microbiology, antimicrobial therapy and epidemiology, Academician V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology, Ministry of Health of Russian Federation, +7(910)414-56-16,,
117997, Russia, Moscow, Ac. Oparin str., 4.
Corresponding author: Galina E. Chernukha,

Authors' contributions: Pronina V.A., Chernukha G.E. – material collection and processing; writing the text; Chernukha G.E., Priputnevich T.V. – editing.
Conflicts of interest: The authors declare that there are no possible conflicts of interest.
Funding: The investigation has been conducted within the research “Elaboration of an integrated approach to diagnosing hormone-related diseases and endometrial functional disorders on the basis of a microbiota study” 122020900123-4.
For citation: Chernukha G.E., Pronina V.A., Priputnevich T.V.
Gut and genital microbiota in endometriosis.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2022; 8: 22-29 (in Russian)

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