The role of the uterine microbiota in the genesis of endometrial polyps

Vanakova A.I., Dolgushina N.V., Priputnevich T.V.

1) Academician V.I. Kulakov National Medical Research Centre for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, Moscow, Russia; 2) I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), Moscow, Russia

Endometrial polyps refer to benign intrauterine pathology. Their etiology is not completely known. One of the possible factors for the development of endometrial polyps is altered microbiota of the uterine cavity. A number of scientific studies have proved that the endometrial microbiota composition is different from the one of the vaginal and cervical microbiota. This concept enabled the scientists to reject the null hypothesis of a “sterile” uterine cavity. There was a suggestion to distinguish the Lactobacillus-dominated endometrial microbiota (≥90%) and the Lactobacillus-deficient microbiota (<90%). According to the literature data, various types of benign intrauterine pathology show differences in the endometrial microbiological composition. The uterine microbiota includes anaerobic and aerobic bacteria in women with endometrial polyps. Previously, endometrial polyps were considered to be a manifestation of chronic endometritis due to reactive proliferation of the endometrium with prolonged mechanical stimulation or exposure to biological factors of inflammation. To date, there are data on the difference in the endometrial microbiota composition in patients with endometrial polyps in combination with chronic endometritis and without it.
Conclusion: Further study of the endometrial microbiota may provide new opportunities for further improvement of the diagnosis and treatment strategies of endometrial polyps and chronic endometritis. 

Authors’ contributions: Dolgushina N.V. – developing the concept and design of the study; Vanakova A.I., Dolgushina N.V. – collecting the material, writing the text; Priputnevich T.V. – editing the data.
Conflicts of interest: The authors declare no conflicts of interest.
Funding: The study was conducted without sponsorship.
For citation: Vanakova A.I., Dolgushina N.V., Priputnevich T.V. The role of the uterine microbiota in the genesis of endometrial polyps. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2023; (11): 43-47 (in Russian)
https://dx.doi.org/10.18565/aig.2023.201

Keywords

uterine microbiota
endometrial polyp
microbiota
16S rRNA gene sequencing
chronic endometritis

References

  1. Nijkang N.P., Anderson L., Markham R., Manconi F. Endometrial polyps: pathogenesis, sequelae and treatment. SAGE Open Med. 2019; 7: 2050312119848247. https://dx.doi.org/10.1177/2050312119848247.
  2. Fatemi H.M., Kasius J.C., Timmermans A., van Disseldorp J., Fauser B.C., Devroey P., Broekmans F.J. Prevalence of unsuspected uterine cavity abnormalities diagnosed by office hysteroscopy prior to in vitro fertilization. Hum. Reprod. 2010; 25(8): 1959-65. https://dx.doi.org/10.1093/humrep/deq150.
  3. Paradisi R., Rossi S., Scifo M.C., Dall'O' F., Battaglia C., Venturoli S. Recurrence of endometrial polyps. Gynecol. Obstet. Invest. 2014; 78(1): 26-32. https://dx.doi.org/ 10.1159/000362646.
  4. AlHilli M.M., Nixon K.E., Hopkins M.R., Weaver A.L., Laughlin-Tommaso S.K., Famuyide A.O. Long-term outcomes after intrauterine morcellation vs hysteroscopic resection of endometrial polyps. J. Minim. Invasive. Gynecol. 2013; 20(2): 215-21. https://dx.doi.org /10.1016/j.jmig.2012.10.013.
  5. Yang J.H., Chen C.D., Chen S.U., Yang Y.S., Chen M.J. Factors influencing the recurrence potential of benign endometrial polyps after hysteroscopic polypectomy. PLoS One. 2015; 10(12): e0144857. https://dx.doi.org/10.1371/journal.pone.0144857.
  6. Clark T.J., Stevenson H. Endometrial polyps and abnormal uterine bleeding (AUB-P): What is the relationship, how are they diagnosed and how are they treated? Best Pract. Res. Clin. Obstet. Gynaecol. 2017; 40: 89-104. https://dx.doi.org/10.1016/j.bpobgyn.2016.09.005.
  7. Di Spiezio Sardo A., Di Carlo C., Minozzi S., Spinelli M., Pistotti V., Alviggi C. et al. Efficacy of hysteroscopy in improving reproductive outcomes of infertile couples: a systematic review and meta-analysis. Hum. Reprod. Update. 2016; 22(4): 479-96. https://dx.doi.org/ 10.1093/humupd/dmw008.
  8. Cicinelli E., Bettocchi S., de Ziegler D., Loizzi V., Cormio G., Marinaccio M. et al. Chronic endometritis, a common disease hidden behind endometrial polyps in premenopausal women: first evidence from a case-control study. J. Minim. Invasive Gynecol. 2019; 26(7): 1346-50. https://dx.doi.org/10.1016/j.jmig.2019.01.012.
  9. Indraccolo U., Di Iorio R., Matteo M., Corona G., Greco P., Indraccolo S.R. The pathogenesis of endometrial polyps: a systematic semi-quantitative review. Eur. J. Gynaecol. Oncol. 2013; 34(1): 5-22.
  10. Ansbacher R., Boyson W.A., Morris J.A. Sterility of the uterine cavity. Am. J. Obstet. Gynecol. 1967; 99(3): 394-6. https://dx.doi.org/10.1016/s0002-9378(16)34549-5.
  11. Mitchell C.M., Haick A., Nkwopara E., Garcia R., Rendi M., Agnew K., Fredricks D.N., Eschenbach D. Colonization of the upper genital tract by vaginal bacterial species in nonpregnant women. Am. J. Obstet. Gynecol. 2015; 212(5): 611.e1-9. https://dx.doi.org /10.1016/j.ajog.2014.11.043.
  12. Verstraelen H., Vilchez-Vargas R., Desimpel F., Jauregui R., Vankeirsbilck N., Weyers S. et al. Characterisation of the human uterine microbiome in non-pregnant women through deep sequencing of the V1-2 region of the 16S rRNA gene. PeerJ. 2016; 4: e1602. .https://dx.doi.org/10.7717/peerj.1602.
  13. Giudice L.C. Challenging dogma: the endometrium has a microbiome with functional consequences! Am. J. Obstet. Gynecol. 2016; 215(6): 682-3. https://dx.doi.org/ 10.1016/j.ajog.2016.09.085.
  14. 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. https://dx.doi.org/10.1038/s41467-017-00901-0.
  15. Miles S.M., Hardy B.L., Merrell D.S. Investigation of the microbiota of the reproductive tract in women undergoing a total hysterectomy and bilateral salpingo-oopherectomy. Fertil. Steril. 2017; 107(3): 813-20. https://dx.doi.org/10.1016/j.fertnstert.2016.11.028.
  16. Koedooder R., Mackens S., Budding A., Fares D., Blockeel C., Laven J., Schoenmakers S. Identification and evaluation of the microbiome in the female and male reproductive tracts. Hum. Reprod. Update. 2019; 25(3): 298-325. https://dx.doi.org/10.1093/humupd/dmy048.
  17. Zhu N., Yang X., Liu Q., Chen Y., Wang X., Li H., Gao H. "Iron triangle" of regulating the uterine microecology: endometrial microbiota, immunity and endometrium. Front. Immunol. 2022; 9:(13): 928475. https://dx.doi.org/10.3389/fimmu.2022.928475.
  18. 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. [Keburiya L.K., Smolnikova V.Yu., Priputnevich T.V., Muravieva V.V. Uterine microbiota and its effect on reproductive outcomes. Obstetrics and Gynecology. 2019; (2): 22-7. (in Russian)]. https://dx.doi.org/10.18565/aig.2019.2.22-27.
  19. Peterson J., Garges S., Giovanni M., McInnes P., Wang L., Schloss J.A. et al. The NIH Human Microbiome Project. Genome Res. 2009; 19(12): 2317-23. https://dx.doi.org/10.1101/gr.096651.109.
  20. Cicinelli E., De Ziegler D., Nicoletti R., Tinelli R., Saliani N., Resta L. et al. Poor reliability of vaginal and endocervical cultures for evaluating microbiology of endometrial cavity in women with chronic endometritis. Gynecol. Obstet. Invest. 2009; 68(2): 108-15. https://dx.doi.org/10.1159/000223819.
  21. Kitaya K., Matsubayashi H., Yamaguchi K., Nishiyama R., Takaya Y., Ishikawa T. et al. Chronic Endometritis: potential cause of infertility and obstetric and neonatal complications. Am. J. Reprod. Immunol. 2016; 75(1): 13-22. https://dx.doi.org/10.1111/aji.12438.
  22. Liang J., Li M., Zhang L., Yang Y., Jin X., Zhang Q. et al. Analysis of the microbiota composition in the genital tract of infertile patients with chronic endometritis or endometrial polyps. Front. Cell Infect. Microbiol. 2023; 22(13): 1125640. https://dx.doi.org/ 10.3389/fcimb.2023.1125640.
  23. Riganelli L., Iebba V., Piccioni M., Illuminati I., Bonfiglio G., Neroni B. et al. Structural variations of vaginal and endometrial microbiota: hints on female infertility. Front. Cell Infect. Microbiol. 2020; 14(10): 350. https://dx.doi.org/10.3389/fcimb.2020.00350.
  24. Moore D.E., Soules M.R., Klein N.A., Fujimoto V.Y., Agnew K.J., Eschenbach D.A. Bacteria in the transfer catheter tip influence the live-birth rate after in vitro fertilization. Fertil. Steril. 2000; 74(6): 1118-24. https://dx.doi.org/10.1016/s0015-0282(00)01624-1.
  25. Moreno I., Codoñer F.M., Vilella F., Valbuena D., Martinez-Blanch J.F., Jimenez-Almazán J. et al. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am. J. Obstet. Gynecol. 2016; 215(6): 684-703. https://dx.doi.org/10.1016/j.ajog.2016.09.075.
  26. Franasiak J.M., Werner M.D., Juneau C.R., Tao X., Landis J., Zhan Y. et al. Endometrial microbiome at the time of embryo transfer: next-generation sequencing of the 16S ribosomal subunit. J. Assist. Reprod. Genet. 2016; 33(1): 129-36. https://dx.doi.org/10.1007/s10815-015-0614-z.
  27. Critchley H.O.D., Babayev E., Bulun S.E., Clark S., Garcia-Grau I., Gregersen P.K. et al. Menstruation: science and society. Am. J. Obstet. Gynecol. 2020; 223(5): 624-64. https://dx.doi.org/10.1016/j.ajog.2020.06.004.
  28. Kadogami D., Nakaoka Y., Morimoto Y. Use of a vaginal probiotic suppository and antibiotics to influence the composition of the endometrial microbiota. Reprod. Biol. 2020; 20(3): 307-14. https://dx.doi.org/10.1016/j.repbio.2020.07.001.
  29. Pelzer E.S., Willner D., Buttini M., Huygens F. A role for the endometrial microbiome in dysfunctional menstrual bleeding. Antonie Van Leeuwenhoek. 2018; 111(6): 933-43. doi: 10.1007/s10482-017-0992-6.
  30. Margulies S.L., Flores V., Parkash V., Pal L. Chronic endometritis: a prevalent yet poorly understood entity. Int. J. Gynaecol. Obstet. 2022; 158(1): 194-200. https://dx.doi.org/10.1002/ijgo.13962.
  31. Kubyshkin A.V., Aliev L.L., Fomochkina I.I., Kovalenko Y.P., Litvinova S.V., Filonenko T.G. et al. Endometrial hyperplasia-related inflammation: its role in the development and progression of endometrial hyperplasia. Inflamm. Res. 2016; 65(10): 785-94. https://dx.doi.org/10.1007/s00011-016-0960-z.
  32. Cai L. Preliminary study on the mechanism of uterine flora on the occurrence and development of endometrial hyperplasia. Jinan University. 2021; 2: 44. https://doi.org/10.27167/d.cnki.gjinu.2019.000458.
  33. Khan K.N., Fujishita A., Masumoto H., Muto H., Kitajima M., Masuzaki H., Kitawaki J. Molecular detection of intrauterine microbial colonization in women with endometriosis. Eur. J. Obstet. Gynecol. Reprod. Biol. 2016; 199: 69-75. https://dx.doi.org/10.1016/j.ejogrb.2016.01.040.
  34. Khan K.N., Fujishita A., Kitajima M., Hiraki K., Nakashima M., Masuzaki H. Intra-uterine microbial colonization and occurrence of endometritis in women with endometriosis. Hum. Reprod. 2014; 29(11): 2446-56. https://dx.doi.org/10.1093/humrep/deu222.
  35. Fang R.L., Chen L.X., Shu W.S., Yao S.Z., Wang S.W., Chen Y.Q. Barcoded sequencing reveals diverse intrauterine microbiomes in patients suffering with endometrial polyps. Am. J. Transl. Res. 2016; 8(3): 1581-92.
  36. Teame T., Wang A., Xie M., Zhang Z., Yang Y., Ding Q. Paraprobiotics and postbiotics of probiotic Lactobacilli, their positive effects on the host and action mechanisms: a review. Front. Nutr. 2020; 22(7): 570344. https://dx.doi.org/10.3389/fnut.2020.570344.
  37. Wang J., Li Z., Ma X., Du L., Jia Z., Cui X. et al. Translocation of vaginal microbiota is involved in impairment and protection of uterine health. Nat. Commun. 2021; 12(1): 4191. https://dx.doi.org/10.1038/s41467-021-24516-8.
  38. Qiu T., Liu L., Zhou H., Sheng H., He Y., Liu M., Cai H. Analysis of endometrial microbiota in intrauterine adhesion by high-throughput sequencing. Ann. Transl. Med. 2021; 9(3): 195. https://dx.doi.org/10.21037/atm-20-2813.

Received 21.08.2023

Accepted 17.10.2023

About the Authors

Angelina I. Vanakova, graduate student of the Department of Obstetrics, Gynecology, Perinatology and Reproductology, IPE, I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia (Sechenov University), +7(903)108-17-90, angelinavanakova@gmail.com, https://orcid.org/0009-0007-8048-1682,
119991, Russia, Moscow, Trubetskaya str., 8-2.
Nataliya V. Dolgushina, Dr. Med. Sci., Professor, Deputy Director, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, n_dolgushina@oparina4.ru, https://orcid.org/0000-0003-1116-138X, 117997, Russia, Moscow, Ac. Oparin str., 4.
Tatiana V. Priputnevich, Corresponding Member of the RAS, Dr. Med. Sci., Director of the Institute of Microbiology, Antimicrobial Therapy and Epidemiology, Academician
V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, +7(910)414-56-16, priput1@gmail.com,
https://orcid.org/0000-0002-4126-9730, 117997, Russia, Moscow, Ac. Oparin str., 4.

Similar Articles

By continuing to use our site, you consent to the processing of cookies that ensure the proper functioning of the site.