Features of the reproductive tract microbiota in patients with genital endometriosis. A literature review

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Abstract

BACKGROUND: Due to the widespread prevalence, steady growth and insufficient effectiveness of existing treatment regimens for external genital endometriosis, further study of the etiology and pathogenesis of the disease remains relevant. Inflammation is known to be one of the links in the pathogenesis of endometriosis; therefore, there is reason to believe that microorganisms are involved in the pathogenesis of this disease.

AIM: The aim of this study was to analyze the role of the reproductive tract microbiota in patients with endometriosis.

MATERIALS AND METHODS: This literature review was performed using systematic reviews, meta-analyses and experimental studies from such electronic databases as PubMed, CyberLeninka, and ScienceDirect published in the period from 1992 to 2021.

RESULTS AND CONCLUSIONS: In the review, we present the pathogenetic relationship between pelvic inflammatory diseases and endometriosis. The quantitatively and qualitatively altered microbiota composition of the reproductive tract, the genetic-epigenetic theory on the pathogenesis of endometriosis, which is based on mutations that accumulate directly under the influence of infectious agents, as well as the mechanisms of an abnormal immune response modeled by microorganisms, reflect the interconnection between the microbiota and the pathogenesis of endometriosis. Based on a number of studies, the relationship between the intestinal microbiota and the abdominal microbiome has been confirmed. Since endometriosis is the estrogen-dependent disease, of importance is the ability of the intestinal microbiota to produce β-glucuronidase, which is enhanced by gut microbial dysbiosis, thus possibly contributing to the progression of endometriosis. One of the important practical directions is the drug correction of dysbiotic conditions. The effectiveness of antibiotic therapy has been demonstrated by experimentally induced endometriosis model. Currently, there are very few highly specific methods for non-invasive diagnosis of the disease, therefore, the study of the reproductive tract and intestinal microflora of women with endometriosis is promising for the introduction of new laboratory diagnostic methods.

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About the authors

Olga E. Kazymova

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott

Author for correspondence.
Email: olia.merk@yandex.ru
ORCID iD: 0000-0003-3869-010X
SPIN-code: 5986-3469

MD

Russian Federation, 3, Mendeleevskaya Line, Saint Petersburg, 199034

Maria I. Yarmolinskaya

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott; North-Western State Medical University named after I.I. Mechnikov

Email: m.yarmolinskaya@gmail.com
ORCID iD: 0000-0002-6551-4147
SPIN-code: 3686-3605
Scopus Author ID: 7801562649
ResearcherId: P-2183-2014

MD, Dr. Sci. (Med.), Professor, Professor of the Russian Academy of Sciences

Russian Federation, 3, Mendeleevskaya Line, Saint Petersburg, 199034; Saint Petersburg

Alevtina M. Savicheva

The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott; Saint Petersburg State Pediatric Medical University

Email: savitcheva@mail.ru
ORCID iD: 0000-0003-3870-5930
SPIN-code: 8007-2630
Scopus Author ID: 6602838765
ResearcherId: P-6788-2015

MD, Dr. Sci. (Med.), Professor, Honored Scientist of the Russian Federation

Russian Federation, 3, Mendeleevskaya Line, Saint Petersburg, 199034; Saint Petersburg

References

  1. Jarmolinskaja MI, Ajlamazjan JeK. Genital’nyj jendometrioz. Razlichnye grani problemy. Saint Petersburg: Jeko-Vektor; 2017.
  2. Khan KN, Fujishita A, Hiraki K, et al. Bacterial contamination hypothesis: a new concept in endometriosis. Reprod Med Biol. 2018;17(2):125−133. doi: 10.1002/rmb2.12083
  3. Laschke MW, Menger MD. The gut microbiota: a puppet master in the pathogenesis of endometriosis? Am J Obstet Gynecol. 2016;215(1):68.e1−4. doi: 10.1016/j.ajog.2016.02.036
  4. Sampson JA. Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous circulation. Am J Pathol. 1927;3(2):93−110.43.
  5. Jacobson L. Endometriosis with infection of the small pelvis. Nord Med. 1960;64:844−847.
  6. Jiang I, Yong PJ, Allaire C, Bedaiwy MA. Intricate connections between the microbiota and endometriosis. Int J Mol Sci. 2021;22(11):5644. doi: 10.3390/ijms22115644
  7. France MT, Ma B, Gajer P, et al. VALENCIA: a nearest centroid classification method for vaginal microbial communities based on composition. Microbiome. 2020;8(1):166. doi: 10.1186/s40168-020-00934-6
  8. Baker JM, Chase DM, Herbst-Kralovetz MM. Uterine microbiota: Residents, tourists, or invaders? Front Immunol. 2018;9:208. doi: 10.3389/fimmu.2018.00208
  9. Bedaiwy MA. Endometrial macrophages, endometriosis, and microbiota: time to unravel the complexity of the relationship. Fertil Steril. 2019;112(6):1049−1050. doi: 10.1016/j.fertnstert.2019.09.021
  10. Ata B, Yildiz S, Turkgeldi E, et al. 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. doi: 10.1038/s41598-019-39700-6
  11. Elizur SE, Lebovitz O, Weintraub AY, et al. Pelvic inflammatory disease in women with endometriosis is more severe than in those without. Aust NZJ Obstet Gynaecol. 2014;54(2):162−165. doi: 10.1111/ajo.12189
  12. Tai FW, Chang CY, Chiang JH, et al. Association of pelvic inflammatory disease with risk of endometriosis: A nationwide cohort study involving 141,460 individuals. J Clin Med. 2018;7(11):379. doi: 10.3390/jcm7110379
  13. Lin WC, Chang CY, Hsu YA, et al. Increased risk of endometriosis in patients with lower Genital tract infection: A nationwide cohort study. Medicine (Baltimore). 2016;95(10):e2773. doi: 10.1097/MD.0000000000002773
  14. Takebayashi A, Kimura F, Kishi Y, et al. The association between endometriosis and chronic endometritis. PLoS One. 2014;9(2):e88354. doi: 10.1371/journal.pone.0088354
  15. Cicinelli E, Trojano G, Mastromauro M, et al. Higher prevalence of chronic endometritis in women with endometriosis: a possible etiopathogenetic link. Fertil Steril. 2017;108(2):289−295.e1. doi: 10.1016/j.fertnstert.2017.05.016
  16. Tolibova GH, Tral’ TG, Jarmolinskaja MI, Cypurdeeva AA. Jendometrial’naja disfunkcija u pacientok s besplodiem, associirovannym s naruzhnym genital’nym jendometriozom. Journal of Obstetrics and Women’s Diseases. 2017;66(Suppl):84−85. (In Russ.)
  17. Koninckx PR, Ussia A, Adamyan L, et al. Pathogenesis of endometriosis: the genetic/epigenetic theory. Fertil Steril. 2019;111(2):327−340. doi: 10.1016/j.fertnstert.2018.10.013
  18. O’Day DH, Taylor RJ, Myre MA. Calmodulin and calmodulin binding proteins in dictyostelium: A primer. Int J Mol Sci. 2020;21(4):1210. doi: 10.3390/ijms21041210
  19. Zhang T, De Carolis C, Man GCW, et al. The link between immunity, autoimmunity and endometriosis: a literature update. Autoimmun Rev. 2018;17(10):945−955. doi: 10.1016/j.autrev.2018.03.017
  20. Scutiero G, Iannone P, Bernardi G, et al. Oxidative stress and endometriosis: A systematic review of the literature. Oxid Med Cell Longev. 2017;2017:7265238. doi: 10.1155/2017/7265238
  21. Bierne H, Hamon M, Cossart P. Epigenetics and bacterial infections. Cold Spring Harb Perspect Med. 2012;2(12):a010272. doi: 10.1101/cshperspect.a010272
  22. Milavetz BI, Balakrishnan L. Viral epigenetics. Methods Mol Biol. 2015;1238:569−596. doi: 10.1007/978-1-4939-1804-1_30
  23. Campos GB, Marques LM, Rezende IS, et al. Mycoplasma genitalium can modulate the local immune response in patients with endometriosis. Fertil Steril. 2018;109(3):549−560.e4. doi: 10.1016/j.fertnstert.2017.11.009
  24. Khan KN, Kitajima M, Inoue T, et al. 17β-estradiol and lipopolysaccharide additively promote pelvic inflammation and growth of endometriosis. Reprod Sci. 2015;22(5):585−594. doi: 10.1177/1933719114556487
  25. Sheldon IM, Owens SE, Turner ML. Innate immunity and the sensing of infection, damage and danger in the female genital tract. J Reprod Immunol. 2017;119:67−73. doi: 10.1016/j.jri.2016.07.002
  26. Laux-Biehlmann A, d’Hooghe T, Zollner TM. Menstruation pulls the trigger for inflammation and pain in endometriosis. Trends Pharmacol Sci. 2015;36(5):270−276. doi: 10.1016/j.tips.2015.03.004
  27. Symons LK, Miller JE, Kay VR, et al. The immunopathophysiology of endometriosis. Trends Mol Med. 2018;24(9):748−762. doi: 10.1016/j.molmed.2018.07.004
  28. Pinto V, Matteo M, Tinelli R, et al. Altered uterine contractility in women with chronic endometritis. Fertil Steril. 2015;103(4):1049−1052. doi: 10.1016/j.fertnstert.2015.01.007
  29. Agostinis C, Mangogna A, Bossi F, et al. Uterine immunity and microbiota: A shifting paradigm. Front Immunol. 2019;10:2387. doi: 10.3389/fimmu.2019.02387
  30. Chen C, Song X, Wei W, et al. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat Commun. 2017;8(1):875. doi: 10.1038/s41467-017-00901-0
  31. Khan KN, Fujishita A, Masumoto H, et al. Molecular detection of intrauterine microbial colonization in women with endometriosis. Eur J Obstet Gynecol Reprod Biol. 2016;199:69−75. doi: 10.1016/j.ejogrb.2016.01.040
  32. Cregger MA, Braundmeier A, Lenz K, et al. Reproductive microbiomes: Using the microbiome as a novel diagnostic tool for endometriosis. Reproduct Immunol Open Access. 2017;2(3). doi: 10.21767/2476-1974.100036
  33. Khan KN, Kitajima M, Hiraki K, et al. Escherichia coli contamination of menstrual blood and effect of bacterial endotoxin on endometriosis. Fertil Steril. 2010;94(7):2860-3.e1−3. doi: 10.1016/j.fertnstert.2010.04.053
  34. Leonardi M, Hicks C, El-Assaad F, et al. Endometriosis and the microbiome: a systematic review. BJOG. 2020;127(2):239−249. doi: 10.1111/1471-0528.15916
  35. Khan KN, Fujishita A, Kitajima M, et al. Intra-uterine microbial colonization and occurrence of endometritis in women with endometriosis†. Hum Reprod. 2014;29(11):2446−2456. doi: 10.1093/humrep/deu222
  36. Wei W, Zhang X, Tang H, et al. Microbiota composition and distribution along the female reproductive tract of women with endometriosis. Ann Clin Microbiol Antimicrob. 2020;19(1):15. doi: 10.1186/s12941-020-00356-0
  37. Wang XM, Ma ZY, Song N. Inflammatory cytokines IL-6, IL-10, IL-13, TNF-α and peritoneal fluid flora were associated with infertility in patients with endometriosis. Eur Rev Med Pharmacol Sci. 2018;22(9):2513−2518. doi: 10.26355/eurrev_201805_14899
  38. Kobayashi H, Higashiura Y, Shigetomi H, et al. Pathogenesis of endometriosis: the role of initial infection and subsequent sterile inflammation (Review). Mol Med Rep. 2014;9(1):9−15. doi: 10.3892/mmr.2013.1755
  39. Wu QJ, Guo M, Lu ZM, et al. Detection of human papillomavirus-16 in ovarian malignancy. Br J Cancer. 2003;89(4):672−675. doi: 10.1038/sj.bjc.6601172
  40. Oppelt P, Renner SP, Strick R, al. Correlation of high-risk human papilloma viruses but not of herpes viruses or Chlamydia trachomatis with endometriosis lesions. Fertil Steril. 2010;93(6):1778−1786. doi: 10.1016/j.fertnstert.2008.12.061
  41. Heidarpour M, Derakhshan M, Derakhshan-Horeh M, et al. Prevalence of high-risk human papillomavirus infection in women with ovarian endometriosis. J Obstet Gynaecol Res. 2017;43(1):135−139. doi: 10.1111/jog.13188
  42. Vestergaard AL, Knudsen UB, Munk T, et al. Low prevalence of DNA viruses in the human endometrium and endometriosis. Arch Virol. 2010;155(5):695−703. doi: 10.1007/s00705-010-0643-y
  43. Rocha RM, Souza RP, Gimenes F, et al. The high-risk human papillomavirus continuum along the female reproductive tract and its relationship to infertility and endometriosis. Reprod Biomed Online. 2019;38(6):926−937. doi: 10.1016/j.rbmo.2018.11.032
  44. Akiyama K, Nishioka K, Khan KN, et al. Molecular detection of microbial colonization in cervical mucus of women with and without endometriosis. Am J Reprod Immunol. 2019;82(2):e13147. doi: 10.1111/aji.13147
  45. Chen S, Gu Z, Zhang W, et al. Microbiome of the lower genital tract in Chinese women with endometriosis by 16s-rRNA sequencing technique: a pilot study. Ann Transl Med. 2020;8(21):1440. doi: 10.21037/atm-20-1309
  46. Okamoto N, Uchida A, Takakura K, et al. Suppression by human placental protein 14 of natural killer cell activity. Am J Reprod Immunol. 1991;26(4):137−142. doi: 10.1111/j.1600-0897.1991.tb00713.x
  47. Kanzaki H, Wang HS, Kariya M, et al. Suppression of natural killer cell activity by sera from patients with endometriosis. Am J Obstet Gynecol. 1992;167(1):257−261. doi: 10.1016/s0002-9378(11)91670-6
  48. Lee SR, Lee JC, Kim SH, et al. 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. doi: 10.3390/ijms22094608
  49. Yuan M, Li D, Zhang Z, et al. Endometriosis induces gut microbiota alterations in mice. Hum Reprod. 2018;33(4):607−616. doi: 10.1093/humrep/dex372
  50. Jess T, Frisch M, Jørgensen KT, et al. Increased risk of inflammatory bowel disease in women with endometriosis: a nationwide Danish cohort study. Gut. 2012;61(9):1279−1283. doi: 10.1136/gutjnl-2011-301095
  51. Ervin SM, Li H, Lim L, et al. Gut microbial β-glucuronidases reactivate estrogens as components of the estrobolome that reactivate estrogens. J Biol Chem. 2019;294(49):18586−18599. doi: 10.1074/jbc.RA119.010950
  52. Kitawaki J, Kado N, Ishihara H, et al. Endometriosis: the pathophysiology as an estrogen-dependent disease. J Steroid Biochem Mol Biol. 2002;83(1−5):149−155. doi: 10.1016/s0960-0760(02)00260-1
  53. Jones LA, Sun EW, Martin AM, et al. The ever-changing roles of serotonin. Int J Biochem Cell Biol. 2020;125:105776. doi: 10.1016/j.biocel.2020.105776
  54. Kalinkina OB, Tezikov YuV, Lipatov IS, et al. Study of urogenital tract and gut microbiota in women with stage III and IV ovarian endometriosis. Perm Medical Journal. 2020;37(1):14−21. doi: 10.17816/pmj37114-21
  55. Perrotta AR, Borrelli GM, Martins CO, et al. The vaginal microbiome as a tool to predict rASRM stage of disease in endometriosis: a pilot study. Reprod Sci. 2020;27(4):1064−1073. doi: 10.1007/s43032-019-00113-5
  56. Chadchan SB, Cheng M, Parnell LA, et al. Antibiotic therapy with metronidazole reduces endometriosis disease progression in mice: a potential role for gut microbiota. Hum Reprod. 2019;34(6):1106−1116. doi: 10.1093/humrep/dez041

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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
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