Microbiota of the cervical canal and uterine cavity in hyperplastic diseases of the endometrium: comparative microbiological analysis
Sarkisyan R.M., Gavrilova T.Yu., Priputnevich T.V., Muravieva V.V., Denisov P.A., Goncharuk O.D., Adamyan L.V.
Objective: A comprehensive assessment of the microbiota composition in the cervical canal and endometrium in women with various forms of endometrial hyperplastic processes (EHP) – polyp/endometrial hyperplasia in combination with uterine myoma or adenomyosis – compared to patients without endometrial pathology, followed by the analysis of its potential pathogenetic role in hyperplastic changes in the endometrium.
Materials and methods: The study included 100 women of reproductive age, divided into 4 groups depending on the presence and nature of endometrial hyperplastic processes. Microbiological examination included polymerase chain reaction test (PCR test) of samples obtained from the cervical canal, as well as culture-based analysis of aspirates from the uterine cavity. To characterize microbial communities, an assessment of microbial saturation and biological diversity was carried out using alpha diversity indices (Shannon-Wiener diversity, Simpson diversity, Margalef's richness) and subsequent data statistical processing.
Results: We found that microbial richness and taxonomic diversity were significantly higher in the cervical canal compared to the endometrium in all study groups. The maximum frequency of endometrial sterility was observed in the control group (52%). However, this indicator was lower and amounted to 24% (p=0.042) in a combination of hyperplastic changes with adenomyosis. The leading representatives of normobiota were Lactobacillus jensenii, L. crispatus and L. gasseri. Opportunistic microorganisms, including Gardnerella vaginalis, Escherichia coli and Enterococcus faecalis, were more often detected in the endometrium of patients with EHP, which may indicate the presence of disorder in microbial homeostasis and the potential pathogenetic significance of these microorganisms.
Conclusion: The microbiological analysis revealed a decline in species diversity and an increase in the proportion of opportunistic microorganisms in the endometrium of patients with EHP. Such changes may indicate microbial transformation of the intrauterine environment and the supposed participation of microbiota in the pathogenesis of this pathology. The obtained results confirm the relevance of further research aimed at a detailed study of the interaction mechanisms between microbiota and endometrial tissue structures, as well as an assessment of its impact on the prevention and treatment of EHP.
Authors’ contributions: Adamyan L.V., Gavrilova T.Yu. – study concept and design; Sarkisyan R.M., Gavrilova T.Yu. – biological material collection and processing; Goncharuk O.D., Muravieva V.V. – laboratory processing; Sarkisyan R.M., Denisov P.A. – statistical data analysis, visualization; Sarkisyan R.M. – manuscript composition; Priputnevich T.V., Adamyan L.V. – manuscript editing.
Conflicts of interest: The authors declare no conflicts of interest.
Funding: The study had no sponsorship.
Ethical Approval: The study protocol was approved by the local ethics committee of the Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
Patient Consent for Publication: All patients signed an informed consent for data publication.
Authors' Data Sharing Statement: The data supporting the findings of this study are available on request from the corresponding author after approval from the principal investigator.
For citation: Sarkisyan R.M., Gavrilova T.Yu., Priputnevich T.V., Muravieva V.V., Denisov P.A., Goncharuk O.D., Adamyan L.V. Microbiota of the cervical canal and uterine cavity in hyperplastic diseases of the endometrium: comparative microbiological analysis.
Akusherstvo i Ginekologiya/Obstetreics and Gynecology. 2025; (9): 144-158 (in Russian)
https://dx.doi.org/10.18565/aig.2025.151
Keywords
References
- 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. 2015; 75(1): 13-22. https://dx.doi.org/10.1111/aji.12438
- Кулаков В.И., Адамян Л.В., ред. Лапароскопия и гистероскопия в гинекологии и акушерстве. М.: ПАНТОРИ; 2012. 124 с. [Kulakov V.I., Adamyan L.V., eds. Laparoscopy and Hysteroscopy in Gynecology and Obstetrics. Moscow: PANTORI; 2012. 124 p. (in Russian)].
- Margulies S.L., Flores V., Parkash V., Pal L. Chronic endometritis: a prevalent yet poorly understood entity. Int. J. Gynecol. Obstet. 2022; 158: 194-200. https://dx.doi.org/10.1002/ijgo.13962
- Molina N.M., Sola-Leyva A., Saez-Lara M.J., Plaza-Diaz J., Tubić-Pavlović A., Romero B. et al. New opportunities for endometrial health by modifying uterine microbial composition: present or future? Biomolecules. 2020; 10(4): 593. https://dx.doi.org/10.3390/biom10040593
- American Association of Gynecologic Laparoscopists. AAGL practice report: practice guidelines for the diagnosis and management of endometrial polyps. J. Minim. Invasive Gynecol. 2012; 19(1): 3-10. https://dx.doi.org/10.1016/j.jmig.2011.09.003
- 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
- Lee Y., Kim K.A., Song M.J., Park Y.S., Lee J., Choi J.W. et al. Multiparametric magnetic resonance imaging of endometrial polypoid lesions. Abdom. Radiol. 2020; 45(11): 3869-81. https://dx.doi.org/10.1007/s00261-020-02567-7
- Munro M.G. Uterine polyps, adenomyosis, leiomyomas, and endometrial receptivity. Fertil. Steril. 2019; 111(4): 629-40. https://dx.doi.org/10.1016/j.fertnstert.2019.02.008
- Ванакова А.И., Долгушина Н.В., Припутневич Т.В. Роль микробиоты полости матки в генезе полипов эндометрия. Акушерство и гинекология. 2023; 11: 43-7. [Vanakova A.I., Dolgushina N.V., Priputnevich T.V. The role of the uterine microbiota in the genesis of endometrial polyps. Obstetrics and Gynecology. 2023; (11): 43-7 (in Russian)]. https://dx.doi.org/10.18565/aig.2023.201
- Peric A., Weiss J., Vulliemoz N., Baud D., Stojanov M. Bacterial colonization of the female upper genital tract. Int. J. Mol. Sci. 2019; 20(14): 3405. https://dx.doi.org/10.3390/ijms20143405
- Ворошилина Е.С., Зорников ДЛ, Копосова О.В., Исламиди Д.К., Игнатова К.Ю., Абакумова Е.И., Курбатова Н.В., Плотко Э.Э. Возможности оценки микробиоты полости матки с использованием ПЦР в реальном времени. Вестник РГМУ. 2020; 1: 12-7. [Voroshilina E.S., Zornikov D.L., Koposova O.V., Islamidi D.K., Ignatova K.Yu., Abakumova E.I., Kurbatova N.V., Plotko E.E. The use of real-time PCR for evaluation of endometrial microbiota. Bulletin of RSMU. 2020; 1: 12-7 (in Russian)]. https://dx.doi.org/10.24075/vrgmu.2020.012
- Кебурия Л.К., Смольникова В.Ю., Припутневич Т.В., Муравьева В.В., Калинина Е.А. Микробиота эндометрия и репродуктивный исход в программах вспомогательных репродуктивных технологий. Акушерство и гинекология. 2020; 4: 166-72. [Keburia L.K., Smolnikova V.Yu., Priputnevich T.V., Muravyeva V.V., Kalinina E.A. Endometrial microbiota and reproductive outcome in assisted reproductive technology programs. Obstetrics and Gynecology. 2020; (4): 166-72 (in Russian)]. https://dx.doi.org/10.18565/aig.2020.4.166-172
- Petersdorf K., Groettrup-Wolfers E., Overton P.M., Seitz C., Schulze-Rath R. Endometrial hyperplasia in pre-menopausal women: a systematic review of incidence, prevalence, and risk factors. Eur. J. Obstet. Gynecol. Reprod. Biol. 2022; 271: 158-71. https://dx.doi.org/10.1016/j.ejogrb.2022.02.015
- Beavis A.L., Blechter B., Najjar O., Fader A.N., Katebi Kashi P., Rositch A.F. Identifying women 45 years and younger at elevated risk for endometrial hyperplasia or cancer. Gynecol. Oncol. 2023; 174: 98-105. https://dx.doi.org/10.1016/j.ygyno.2023.04.019
- Walter-Antonio M.R., 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(1): 122. https://dx.doi.org/10.1186/s13073-016-0368-y
- Al-Nasiry S., Ambrosino E., Schlaepfer M., Morré S.A., Wieten L., Voncken J.W. et al. The interplay between reproductive tract microbiota and immunological system in human reproduction. Front. Immunol. 2020; 11: 378. https://dx.doi.org/10.3389/fimmu.2020.00378
- 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-oophorectomy. Fertil Steril. 2017; 107(3): 813-20.e1. https://dx.doi.org/10.1016/j.fertnstert.2016.11.028
- 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.
- Ata B., Yildiz S., Turkgeldi E., Pérez Brocal V., Dinleyici E.C., Moya A. et al. The endobiota study: comparison of vaginal, cervical, and gut microbiota between women with stage III/IV endometriosis and healthy controls. Sci. Rep. 2019; 9(1): 2204. https://dx.doi.org/10.1038/s41598-019-39700-6
- Kimura F., Takebayashi A., Ishida M., Nakamura A., Kitazawa J., Morimune A. et al. Review: chronic endometritis and its effect on reproduction. J. Obstet. Gynaecol. Res. 2019; 45(5): 951-60. https://dx.doi.org/10.1111/jog.13937
- Баринова В.В., Кузнецова Н.Б., Буштырева И.О., Оксенюк О.С., Дудурич В.В., Шаталов А.Е. Микробиом эндометрия при многократных неудачах вспомогательных репродуктивных технологий и у здоровых женщин: где норма и где патология? Акушерство и гинекология. 2021; 6: 105-14. [Barinova V.V., Kuznetsova N.B., Bushtyreva I.O., Oksenyuk O.S., Dudurich V.V., Shatalov A.E. Endometrial microbiome in women with and without a history of repeated failures of assisted reproductive technology: what are norm and pathology? Obstetrics and Gynecology. 2021; (6): 105-14 (in Russian)]. https://dx.doi.org/10.18565/aig.2021.6.105-114
Received 11.06.2025
Accepted 11.09.2025
About the Authors
Rita M. Sarkisyan, PhD student, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, ritamisakovna@mail.ru, https://orcid.org/0000-0002-4097-5537Tatyana Yu. Gavrilova, Dr. Med. Sci., obstetrician-gynecologist at the Gynecological Department, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4, t_gavrilova@oparina4.ru, https://orcid.org/0000-0001-7424-4292
Tatyana V. Priputnevich, Corresponding Member of the Russian Academy of Sciences, 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, 117997, Russia,
Moscow, Ac. Oparin str., 4, priput1@gmail.com, https://orcid.org/0000-0002-4126-9730
Vera V. Muravieva, PhD, Senior Researcher at the Laboratory of Molecular Microbiology, Department of Molecular Microbiology and Bioinformatics, 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, 117997, Russia, Moscow, Ac. Oparin str., 4, v_muravieva@oparina4.ru, https://orcid.org/0000-0003-0383-0731
Pavel A. Denisov, Researcher at the Laboratory of Bioinformatic Analysis, 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, 117997, Russia, Moscow, Ac. Oparin str., 4,
denisov@neuro.nnov.ru, https://orcid.org/0000-0003-1813-6718
Olga D. Goncharuk, Head of the Laboratory of Medical Microbiology, 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, 117997, Russia, Moscow, Ac. Oparin str., 4, o_goncharuk@oparina4.ru, https://orcid.org/0000-0001-5876-8424
Leila V. Adamyan, Academician of the Russian Academy of Sciences, Dr. Med. Sci., Professor, Deputy Director for Research, Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia, 117997, Russia, Moscow, Ac. Oparin str., 4; Chief Specialist in Gynecology of
the Ministry of Health of Russia; Head of the Department of Reproductive Medicine and Surgery of the Faculty of Postgraduate Education, Russian University of Medicine, Ministry of Health of Russia, adamyanleila@gmail.com, https://orcid.org/0000-0002-3253-4512
Corresponding author: Rita M. Sarkisyan, ritamisakovna@mail.ru