fcmedicineФундаментальная и клиническая медицинаFundamental and Clinical Medicine2500-07642542-0941КемГМУ10.23946/2500-0764-2024-9-1-102-111fcmedicine-829Research ArticleОБЗОРНЫЕ СТАТЬИREVIEW ARTICLESРезидентная микробиота эндометрияGeneral Overview of Endometrial Microbiotahttps://orcid.org/0000-0002-0536-2874ГоловешкинаЕ. Н.GoloveshkinaE. N.

Головешкина Елена Николаевна, кандидат биологических наук, заведующая лабораторией молекулярной диагностики и эпидемиологии инфекций органов репродукции

111123, г. Москва, ул. Новогиреевская, д. 3а

Dr. Elena N. Goloveshkina, PhD, Head of the Laboratory for Epidemiology of Reproductive Tract Infections

3a, Novogireevskaya Street, Moscow, 111123 

elenagoloveshkina@yandex.ruhttps://orcid.org/0000-0003-1924-6521СкачковаТ. С.SkachkovaT. S.

Скачкова Татьяна Сергеевна, старший научный сотрудник лаборатории молекулярной диагностики и эпидемиологии инфекций органов репродукции

111123, г. Москва, ул. Новогиреевская, д. 3а

Dr. Tatiana S. Skachkova, MD, PhD, Senior Researcher, Laboratory for Epidemiology of Reproductive Tract Infections

3a, Novogireevskaya Street, Moscow, 111123 

https://orcid.org/0000-0003-4228-9044АкимкинВ. Г.AkimkinV. G.

Акимкин Василий Геннадьевич, академик РАН, доктор медицинских наук, профессор, директор

111123, г. Москва, ул. Новогиреевская, д. 3а

Prof. Vasiliy G. Akimkin, MD, DSc, Professor, Academician of the Russian Academy of Sciences, Chief Executive Officer

3a, Novogireevskaya Street, Moscow, 111123 

ФБУН «Центральный научно-исследовательский институт эпидемиологии» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека»РоссияCentral Research Institute of Epidemiology of RospotrebnadzorRussian Federation20242903202491102111Copyright © Головешкина Е.Н., Скачкова Т.С., Акимкин В.Г., 20242024Головешкина Е.Н., Скачкова Т.С., Акимкин В.Г.Goloveshkina E.N., Skachkova T.S., Akimkin V.G.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://fcm.kemsmu.ru/jour/article/view/829

Цель обзора. Изучение современного состояния научных знаний, описывающих микробиом эндометрия. Полость матки считалась стерильной до второй половины 20-го века. Развитие методов молекулярной биологии, таких как ПЦР и секвенирование, позволило провести множество исследований по описанию различных микробных сообществ внутри полости матки. Было показано, что среднее количество бактерий в матке ниже, чем во влагалище, на 2-4 десятичных логарифма. В научных публикациях описывается различный спектр основных микроорганизмов. В одних исследованиях доминирующими микроорганизмами в эндометрии были Lactobacillus, в других преобладания данных микроорганизмов показано не было. Несмотря на многочисленные исследования, консенсус относительно физиологического ядра микробиома полости матки не был достигнут из-за ряда ограничений исследований, таких как возможная контаминация реагентов для проведения молекулярно-биологического анализа и при заборе проб, размер и характеристики выборки, различные вариации дизайна эксперимента. Предполагается, что колонизация матки может происходить восходящим путем из влагалища, со спермой, транслокацией через кровь, а также экзогенным путем, связанным с различными медицинскими процедурами. К настоящему времени проведены исследования, посвященные не только определению состава микробиома эндометрия, но и функциональной активности его представителей. В результате подтверждено наличие живых и функционально активных микроорганизмов в полости матки. Изменения в микробиоме женских половых органов связывают с гинекологическими и акушерскими патологиями, а также с результатами вспомогательной репродукции. Тем не менее, влияние бактериальных сообществ эндометрия на здоровье человека остается спорным, так же как и его состав. Определение состава микробного сообщества матки и его влияния на репродуктивное здоровье женщины остается важной задачей будущих исследований. Изучение взаимосвязей между микробиотой эндометрия и различными заболеваниями может способствовать улучшению диагностики, лечения и профилактики заболеваний женской репродуктивной системы. Для достижения оптимального успеха в будущих исследованиях потребуются хорошо спланированные протоколы, начиная со сбора образцов и заканчивая биоинформационным анализом.

Here, we aimed to summarize the current knowledge describing the endometrial microbiota. The uterine cavity was considered sterile until the second half of the 20th century. The development of molecular biology techniques such as polymerase chain reaction and sequencing enabled many studies to characterise microbial communities inside the uterine cavity. Although the average number of bacteria in the uterus is lower than in the vagina by 2-4 decimal logarithms, their diversity is still remarkable. The physiological core of endometrial microbiome has not been clearly delineated because of technical limitations including possible contamination during sampling, heterogeneity of sequencing techniques, and variations of experimental design. Bacteria might colonise the uterus from vagina, with semen, by translocation through the blood, or during the respective medical procedures. Generally, major alterations of the endometrial microbiota are triggered by gynecological diseases or assisted reproduction. Hitherto, the impact of endometrial microbiota on human health remains controversial. Understanding the relationships between the endometrial microbiota and human diseases can lead to better diagnosis, treatment and prevention of gynecological diseases. To achieve the success, future studies should employ standardized protocols, from sample collection to bioinformatics analysis.

микробиомэндометрийматкарезидентная микробиота маткиmicrobiomeendometriumuterusresident microbiotaReferencesBoyson W.A., Morris J.A. Sterility of the uterine cavity. Am. J. Obstet. Gynecol. 1967;99(3):394-396. https://doi.org/10.1016/s0002-9378(16)34549-5Boyson WA, Morris JA. Sterility of the uterine cavity. Am J Obstet Gynecol. 1967;99(3):394-396. https://doi.org/10.1016/s0002-9378(16)34549-5Heinonen P.K., Teisala K., Punnonen R., Miettinen A., Lehtinen M., Paavonen J. Anatomic sites of upper genital tract infection. Obstet. Gynecol. 1985;66(3):384-390.Heinonen PK, Teisala K, Punnonen R, Miettinen A, Lehtinen M, Paavonen J. Anatomic sites of upper genital tract infection. Obstet Gynecol. 1985;66(3):384-390.Eschenbach D.A., Rosene K., Tompkins L.S., Watkins H., Gravett M.G. Endometrial cultures obtained by a triple-lumen method from afebrile and febrile postpartum women. J. Infect. Dis. 1986;153(6):1038-1045. https://doi.org/10.1093/infdis/153.6.10385Eschenbach DA, Rosene K, Tompkins LS, Watkins H, Gravett MG. Endometrial cultures obtained by a triple-lumen method from afebrile and febrile postpartum women. J Infect Dis. 1986;153(6):10381045. https://doi.org/10.1093/infdis/153.6.10385Hemsell D.L., Obregon V.L., Heard M.C., Nobles B.J. Endometrial bacteria in asymptomatic, nonpregnant women. J. Reprod. Med. 1989;34(11):872-874.Hemsell DL, Obregon VL, Heard MC, Nobles BJ. Endometrial bacteria in asymptomatic, nonpregnant women. J Reprod Med. 1989;34(11):872-874.Moller B.R., Kristiansen F.V., Thorsen P., Frost L., Mogensen S.C. Sterility of the uterine cavity. Acta Obstet. Gynecol. Scand. 1995;74(3):216-219. https://doi.org/10.3109/00016349509008942Moller BR, Kristiansen FV, Thorsen P, Frost L, Mogensen SC. Sterility of the uterine cavity. Acta Obstet Gynecol Scand. 1995;74(3):216-219. https://doi.org/10.3109/00016349509008942Hansen L.K., Becher N., Bastholm S., Glavind J., Ramsing M., Kim C.J., Romero R., Jensen J.S., Uldbjerg N. The cervical mucus plug inhibits, but does not block, the passage of ascending bacteria from the vagina during pregnancy. Acta Obstet. Gynecol. Scand. 2014;93(1):102-108. https://doi.org/10.1111/aogs.12296Hansen LK, Becher N, Bastholm S, Glavind J, Ramsing M, Kim CJ, Romero R, Jensen JS, Uldbjerg N. The cervical mucus plug inhibits, but does not block, the passage of ascending bacteria from the vagina during pregnancy. Acta Obstet Gynecol Scand. 2014;93(1):102-108. https://doi.org/10.1111/aogs.12296Kunz G., Beil D., Deiniger H., Einspanier A., Mall G., Leyendecker G. The uterine peristaltic pump – normal and impeded sperm transport within the female genital tract. Adv. Exp. Med. Biol. 1997;424:267-277. https://doi.org/10.1007/978-1-4615-5913-949Kunz G, Beil D, Deiniger H, Einspanier A, Mall G, Leyendecker G. The uterine peristaltic pump – normal and impeded sperm transport within the female genital tract. Adv Exp Med Biol. 1997;424:267-277. https://doi.org/10.1007/978-1-4615-5913-949Mitchell 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;212:611.e1-611.e9. https://doi.org/10.1016/j.ajog.2014.11.043Mitchell CM, Haick A, Nkwopara E, Garcia R, Rendi M, Agnew K, Fredricks DN, Eschenbach D. Colonization of the upper genital tract by vaginal bacterial species in nonpregnant women. Am J Obstet Gynecol. 2015;212:611.e1-611.e9. https://doi.org/10.1016/j.ajog.2014.11.043Franasiak J.M., Werner M.D., Juneau C.R., Tao X., Landis J., Zhan Y., Treff N.R., Scott R.T. Endometrial microbiome at the time of embryo transfer: next-generation sequencing of the 16S ribosomal subunit. J. Assist. Reprod. Genet. 2016;33(1):129-136. https://doi.org/10.1007/s10815-015-0614-zFranasiak JM, Werner MD, Juneau CR, Tao X, Landis J, Zhan Y, Treff NR, Scott RT. Endometrial microbiome at the time of embryo transfer: next-generation sequencing of the 16S ribosomal subunit. J Assist Reprod Genet. 2016;33(1):129-136. https://doi.org/10.1007/s10815-015-0614-zVerstraelen H., Vilchez-Vargas R., Desimpel F., Jauregui R., Vankeirsbilck N., Weyers S., Verhelst R., De Sutter P., Pieper D.H., Van De Wiele T. 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://doi.org/10.7717/peerj.1602Verstraelen H, Vilchez-Vargas R, Desimpel F, Jauregui R, Vankeirsbilck N, Weyers S, Verhelst R, De Sutter P, Pieper DH, Van De Wiele T. 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://doi.org/10.7717/peerj.1602Molina N.M., Sola-Leyva A., Haahr T., Aghajanova L., Laudanski P., Castilla J.A., Altmäe S. Analysing endometrial microbiome: methodological considerations and recommendations for good practice. Hum. Reprod. 2021;36(4),859-879. https://doi.org/10.1093/humrep/deab009Molina NM, Sola-Leyva A., Haahr T, Aghajanova L, Laudanski P, Castilla JA, Altmäe S. Analysing endometrial microbiome: methodological considerations and recommendations for good practice. Hum Reprod. 2021;36(4),859-879. https://doi.org/10.1093/humrep/deab009Moreno I., Codoner F.M., Vilella F., Valbuena D., Martinez-Blanch J.F., Jimenez-Almaza´n J., Alonso R., Alama´ P., Remohı´ J., Ramon D., Simon C. Evidence that the endometrial microbiota has an effect on implantationsuccess or failure. Am. J. Obstet. Gynecol. 2016;215:684-703. https://doi.org/10.1016/j.ajog.2016.09.075Moreno I, Codoner FM, Vilella F, Valbuena D, Martinez-Blanch JF, Jimenez-Almaza´n J, Alonso R, Alama´ P, Remohı´ J, Ramon D, Simon C. Evidence that the endometrial microbiota has an effect on implantationsuccess or failure. Am J Obstet Gynecol. 2016;215:684- 703. https://doi.org/10.1016/j.ajog.2016.09.075Kyono K., Hashimoto T., Kikuchi S., Nagai Y., Sakuraba Y. A pilot study and case reports on endometrial microbiota and pregnancy outcome: An analysis using 16S rRNA gene sequencing among IVF patients, and trial therapeutic intervention for dysbiotic endometrium. Reprod. Med. Biol. 2019;18:72-82. https://doi.org/10.1002/rmb2.12250Kyono K, Hashimoto T, Kikuchi S, Nagai Y, Sakuraba Y. A pilot study and case reports on endometrial microbiota and pregnancy outcome: An analysis using 16S rRNA gene sequencing among IVF patients, and trial therapeutic intervention for dysbiotic endometrium. Reprod Med Biol. 2019;18:72-82. https://doi.org/10.1002/rmb2.12250Chen C., Song X., Wei W., Zhong H., Dai J., Lan Z., Li F., Yu X., Feng Q., Wang Z., Xie H., Chen X., Zeng C., Wen B., Zeng L., Du H., Tang H., Xu C., Xia Y., Xia H., Yang H., Wang J., Wang J., Madsen L., Brix S., Kristiansen K., Xu X., Li J., Wu R., Jia H. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat. Commun. 2017;8:875. https://doi.org/10.1038/s41467-017-00901-0Chen C, Song X, Wei W, Zhong H, Dai J, Lan Z, Li F, Yu X, Feng Q, Wang Z, Xie H, Chen X, Zeng C, Wen B, Zeng L, Du H, Tang H, Xu C, Xia Y, Xia H, Yang H, Wang J, Wang J, Madsen L, Brix S, Kristiansen K, Xu X, Li J, Wu R, Jia H. The microbiota continuumalong the female reproductive tract and its relation to uterine-related diseases. Nat Commun. 2017;8:875. https://doi.org/10.1038/s41467-017-00901-0Liu Y., Wong K.K., Ko E.Y., Chen X., Huang J., Tsui S.K., Li T.C., Chim S.S. Systematic Comparison of Bacterial Colonization of Endometrial Tissue and Fluid Samples in Recurrent Miscarriage Patients: Implications for Future Endometrial Microbiome Studies. Clin. Chem. 2018;64(12):1743-1752. https://doi.org/10.1373/clinchem.2018.289306Liu Y, Wong KK, Ko EY, Chen X, Huang J, Tsui SK, Li TC, Chim SS. Systematic Comparison of Bacterial Colonization of Endometrial Tissue and Fluid Samples in Recurrent Miscarriage Patients: Implications for Future Endometrial Microbiome Studies. Clin Chem. 2018;64(12):1743-1752. https://doi.org/10.1373/clinchem.2018.289306Leoni C., Ceci O., Manzari C., Fosso B., Volpicella M., Ferrari A., Fiorella P., Pesole G., Cicinelli E., Ceci L.R. Human Endometrial Microbiota at Term of Normal Pregnancies. Genes. 2019;10(12):971. https://doi.org/10.3390/genes10120971Leoni C, Ceci O, Manzari C, Fosso B, Volpicella M, Ferrari A, Fiorella P, Pesole G, Cicinelli E, Ceci LR. Human Endometrial Microbiota at Term of Normal Pregnancies. Genes. 2019;10(12):971. https://doi.org/10.3390/genes10120971Winters A.D., Romero R., Gervasi M.T., Gomez-Lopez N., Tran M.R., Garcia-Flores V., Pacora P., Jung E., Hassan S.S., Hsu C.D., Theis K.R. Does the endometrial cavity have a molecular microbial signature? Sci. Rep. 2019;9:9905. https://doi.org/10.1038/s41598-019-46173-017Winters AD, Romero R, Gervasi MT, Gomez-Lopez N, Tran MR, Garcia-Flores V, Pacora P, Jung E, Hassan SS, Hsu CD, Theis KR. Does the endometrial cavity have a molecular microbial signature? Sci Rep. 2019;9:9905. https://doi.org/10.1038/s41598-019-46173-0Parratt J.R., Taggart M.J., Wray S. Functional effects of intracellular pH alteration in the human uterus: simultaneous measurements of pH and force in Reproduction. J. Reprod. Fertil. 1995;105(1):71-75. https://doi.org/10.1530/jrf.0.1050071Parratt JR, Taggart MJ, Wray S. Functional effects of intracellular pH alteration in the human uterus: simultaneous measurements of pH and force in Reproduction. J. Reprod. Fertil. 1995;105(1):71-75. https://doi.org/10.1530/jrf.0.1050071Кира Е.Ф. Бактериальный вагиноз. M.: Медицинское информационное агентство, 2012. 472 с.Kira EF. Bakterial’nyy vaginoz. Moscow: Meditsinskoe informatsionnoe agentstvo; 2012. (In Russ).Duff P., Gibbs R.S., Blanco J.D., St Clair P.J. Endometrial culture techniques in puerperal patients. Obstet. Gynecol. 1983;61(2):217-222.Duff P, Gibbs RS, Blanco JD, St Clair PJ. Endometrial culture techniques in puerperal patients. Obstet Gynecol. 1983;61(2):217-22.Eisenhofer R., Minich J.J., Marotz C., Cooper A., Knight R., Weyrich L.S. Contamination in low microbial biomass microbiome studies: Issues and Recommendations. Trends Microbiol. 2019;27(2):105-117. https://doi.org/10.1016/j.tim.2018.11.003Eisenhofer R, Minich JJ, Marotz C, Cooper A, Knight R, Weyrich LS. Contamination in low microbial biomass microbiome studies: Issues and Recommendations. Trends Microbiol. 2019;27(2):105-117. https://doi.org/10.1016/j.tim.2018.11.003Glassing A., Dowd S.E., Galandiuk S., Davis B., Chiodini R.J. Inherent bacterial DNA contamination of extraction and sequencing reagents may affect interpretation of microbiota in low bacterial biomass samples. Gut. Pathog. 2016;26(8):24. https://doi.org/10.1186/s13099-016-0103-7Glassing A, Dowd SE, Galandiuk S, Davis B, Chiodini RJ. Inherent bacterial DNA contamination of extraction and sequencing reagents may affect interpretation of microbiota in low bacterial biomass samples. Gut Pathog. 2016;26(8):24. https://doi.org/10.1186/s13099-016-0103-7Winters A.D., Romero R., Gervasi M.T., Gomez-Lopez N., Tran M.R., Garcia-Flores V., Pacora P., Jung E., Hassan S.S., Hsu C.D., Theis K.R. Does the endometrial cavity have a molecular microbial signature? Sci. Rep. 2019;9(1):9905. https://doi.org/10.1038/s41598-019-46173-0Winters AD, Romero R, Gervasi MT, Gomez-Lopez N, Tran MR, Garcia-Flores V, Pacora P, Jung E, Hassan SS, Hsu CD, Theis KR. Does the endometrial cavity have a molecular microbial signature? Sci Rep. 2019;9(1):9905. https://doi.org/10.1038/s41598-019-46173-0Riganelli L., Iebba V., Piccioni M., Illuminati I., Bonfiglio G., Neroni B., Calvo L., Gagliardi A., Levrero M., Merlino L., Mariani M., Capri O., Pietrangeli D., Schippa S., Guerrieri F. Structural Variations of Vaginal and Endometrial Microbiota: Hints on Female Infertility. Front. Cell. Infect. Microbiol. 2020;10:350. https://doi.org/10.3389/fcimb.2020.00350Riganelli L, Iebba V, Piccioni M, Illuminati I, Bonfiglio G, Neroni B, Calvo L, Gagliardi A, Levrero M, Merlino L, Mariani M, Capri O, Pietrangeli D, Schippa S, Guerrieri F. Structural Variations of Vaginal and Endometrial Microbiota: Hints on Female Infertility. Front Cell Infect Microbiol. 2020;10:350. https://doi.org/10.3389/fcimb.2020.00350Jin H., Hu G., Sun C., Duan Y., Zhang Z., Liu Z., Zhao X.M., Chen W.H. mBodyMap: a curated database for microbes across human body and their associations with health and diseases. Nucleic Acids Res. 2022;50(D1):D808-D816. https://doi.org/10.1093/nar/gkab973Jin H, Hu G, Sun C, Duan Y, Zhang Z, Liu Z, Zhao XM, Chen WH. mBodyMap: a curated database for microbes across human body and their associations with health and diseases. Nucleic Acids Res. 2022;50(D1):D808-D816. https://doi.org/10.1093/nar/gkab973Fredricks D.N. Molecular methods to describe the spectrum and dynamics of the vaginal microbiota. Anaerobe. 2011;17(4):191-195. https://doi.org/10.1016/j.anaerobe.2011.01.001Fredricks DN. Molecular methods to describe the spectrum and dynamics of the vaginal microbiota. Anaerobe. 2011;17(4):191-5. https://doi.org/10.1016/j.anaerobe.2011.01.001Heng L., Gao Y., Xia Q., Wang H., Xie X., Liu Y., Shang H., Diao Y. Reproductive tract microbiota of women in childbearing age shifts upon gynecological infections and menstrual cycle. BMC Microbiol. 2021;21(1):252. https://doi.org/10.1186/s12866-021-02300-4Heng L, Gao Y, Xia Q, Wang H, Xie X, Liu Y, Shang H, Diao Y. Reproductive tract microbiota of women in childbearing age shifts upon gynecological infections and menstrual cycle. BMC Microbiol. 2021;21(1):252. https://doi.org/10.1186/s12866-021-02300-4Khan 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://doi.org/10.1016/j.ejogrb.2016.01.040Khan KN, 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://doi.org/10.1016/j.ejogrb.2016.01.040Moreno I., Codoñer F.M., Vilella F., Valbuena D., Martinez-Blanch J.F., Jimenez-Almazán J., Alonso R., Alamá P., Remohí J., Pellicer A., Ramon D., Simon C. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am. J. Obstet. Gynecol. 2016;215(6):684- 703. https://doi.org/10.1016/j.ajog.2016.09.075Moreno I, Codoñer FM, Vilella F, Valbuena D, Martinez-Blanch JF, Jimenez-Almazán J, Alonso R, Alamá P, Remohí J, Pellicer A, Ramon D, Simon C. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am J Obstet Gynecol. 2016;215(6):684-703. https://doi.org/10.1016/j.ajog.2016.09.075Kyono K., Hashimoto T., Nagai Y., Sakuraba Y. Analysis of endometrial microbiota by 16S ribosomal RNA gene sequencing among infertile patients: a single-center pilot study. Reprod. Med. Biol. 2018;17(3):297- 306. https://doi.org/10.1002/rmb2.12105Kyono K, Hashimoto T, Nagai Y, Sakuraba Y. Analysis of endometrial microbiota by 16S ribosomal RNA gene sequencing among infertile patients: a single-center pilot study. Reprod Med Biol. 2018;17(3):297- 306. https://doi.org/10.1002/rmb2.12105Chen C., Song X., Wei W., Zhong H., Dai J., Lan Z., Li F., Yu X., Feng Q., Wang Z., Xie H., Chen X., Zeng C., Wen B., Zeng L., Du H., Tang H., Xu C., Xia Y., Xia H., Yang H., Wang J., Wang J., Madsen L., Brix S., Kristiansen K., Xu X., Li J., Wu R., Jia H. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat. Commun. 2017;8(1):875. https://doi.org/10.1038/s41467-017-00901-0Chen C, Song X, Wei W, Zhong H, Dai J, Lan Z, Li F, Yu X, Feng Q, Wang Z, Xie H, Chen X, Zeng C, Wen B, Zeng L, Du H, Tang H, Xu C, Xia Y, Xia H, Yang H, Wang J, Wang J, Madsen L, Brix S, Kristiansen K, Xu X, Li J, Wu R, Jia H. The microbiota continuum along the female reproductive tract and its relation to uterine-related diseases. Nat Commun. 2017;8(1):875. https://doi.org/10.1038/s41467-017-00901-0Sola-Leyva A., Andrés-León E., Molina N.M., Terron-Camero L.C., Plaza-Díaz J., Sáez-Lara M.J., Gonzalvo M.C., Sánchez R., Ruíz S., Martínez L., Altmäe S. Mapping the entire functionally active endometrial microbiota. Hum. Reprod. 2021;36(4):1021-1031. https://doi.org/10.1093/humrep/deaa372Sola-Leyva A, Andrés-León E, Molina NM, Terron-Camero LC, Plaza-Díaz J, Sáez-Lara MJ, Gonzalvo MC, Sánchez R, Ruíz S, Martínez L, Altmäe S. Mapping the entire functionally active endometrial microbiota. Hum Reprod. 2021;36(4):1021-1031. https://doi.org/10.1093/humrep/deaa372Ravel J., Gajer P., Abdo Z., Schneider G.M., Koenig S.S., McCulle S.L., Karlebach S., Gorle R., Russell J., Tacket C.O., Brotman R.M., Davis C.C., Ault K., Peralta L., Forney L.J. Vaginal microbiome of reproductiveage women. Proc. Natl. Acad. Sci. U S A. 2011;108(Suppl 1):4680-4687. https://doi.org/10.1073/pnas.1002611107Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO, Brotman RM, Davis CC, Ault K, Peralta L, Forney LJ. Vaginal microbiome of reproductiveage women. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4680-4687. https://doi.org/10.1073/pnas.1002611107Wang J., Li Z., Ma X., Du L., Jia Z., Cui X., Yu L., Yang J., Xiao L.,Zhang B., Fan H., Zhao F. Translocation of vaginal microbiota is involved in impairment and protection of uterine health. Nat. Commun. 2021;12(1):4191. https://doi.org/10.1038/s41467-021-24516-8Wang J, Li Z, Ma X, Du L, Jia Z, Cui X, Yu L, Yang J, Xiao L, Zhang B, Fan H, Zhao F. Translocation of vaginal microbiota is involved in impairment and protection of uterine health. Nat Commun. 2021;12(1):4191. https://doi.org/10.1038/s41467-021-24516-8Knight R., Vrbanac A., Taylor B.C., Aksenov A., Callewaert C., Debelius J., Gonzalez A., Kosciolek T., McCall L.I., McDonald D., Melnik A.V., Morton J.T., Navas J., Quinn R.A., Sanders J.G., Swafford A.D., Thompson L.R., Tripathi A., Xu Z.Z., Zaneveld J.R., Zhu Q., Caporaso J.G., Dorrestein P.C. Best practices for analysing microbiomes. Nat. Rev. Microbiol. 2018;16(7):410-422. https://doi.org/10.1038/s41579-018-0029-9Knight R, Vrbanac A, Taylor BC, Aksenov A, Callewaert C, Debelius J, Gonzalez A, Kosciolek T, McCall LI, McDonald D, Melnik AV, Morton JT, Navas J, Quinn RA, Sanders JG, Swafford AD, Thompson LR, Tripathi A, Xu ZZ, Zaneveld JR, Zhu Q, Caporaso JG, Dorrestein PC. Best practices for analysing microbiomes. Nat Rev Microbiol. 2018;16(7):410-422. https://doi.org/10.1038/s41579-018-0029-9Pollock J., Glendinning L., Wisedchanwet T., Watson M. The Madness of Microbiome: Attempting To Find Consensus “Best Practice” for 16S Microbiome Studies. Appl. Environ. Microbiol. 2018;84(7):e02627-17. https://doi.org/10.1128/AEM.02627-17Pollock J, Glendinning L, Wisedchanwet T, Watson M. The Madness of Microbiome: Attempting To Find Consensus “Best Practice” for 16S Microbiome Studies. Appl Environ Microbiol. 2018;84(7):e02627-17. https://doi.org/10.1128/AEM.02627-17Kunz G., Beil D., Deiniger H., Einspanier A., Mall G., Leyendecker G. The uterine peristaltic pump – normal and impeded sperm transport within the female genital tract. Adv. Exp. Med. Biol. 1997;424:267-77. https://doi.org/10.1007/978-1-4615-5913-949Kunz G, Beil D, Deiniger H, Einspanier A, Mall G, Leyendecker G. The uterine peristaltic pump – normal and impeded sperm transport within the female genital tract. Adv Exp Med Biol. 1997;424:267-277. https://doi.org/10.1007/978-1-4615-5913-949Swidsinski A., Verstraelen H., Loening-Baucke V., Swidsinski S., Mendling W., Halwani Z. Presence of a polymicrobial endometrial biofilm in patients with bacterial vaginosis. PLoS One. 2013;8(1):e53997. https://doi.org/10.1371/journal.pone.0053997Swidsinski A, Verstraelen H, Loening-Baucke V, Swidsinski S, Mendling W, Halwani Z. Presence of a polymicrobial endometrial biofilm in patients with bacterial vaginosis. PLoS One. 2013;8(1):e53997. https://doi.org/10.1371/journal.pone.0053997Svenstrup H.F., Fedder J., Abraham-Peskir J., Birkelund S., Christiansen G. Mycoplasma genitalium attaches to human spermatozoa. Hum. Reprod. 2003;18(10):2103-2109. https://doi.org/10.1093/humrep/deg392Svenstrup HF, Fedder J, Abraham-Peskir J, Birkelund S, Christiansen G. Mycoplasma genitalium attaches to human spermatozoa. Hum Reprod. 2003;18(10):2103-2109. https://doi.org/10.1093/humrep/deg392Sparks R.A., Purrier B.G., Watt P.J., Elstein M. Bacteriological colonisation of uterine cavity: role of tailed intrauterine contraceptive device. Br. Med. J. (Clin. Res. Ed). 1981;282(6271):1189-1191. https://doi.org/10.1136/bmj.282.6271.1189Sparks RA, Purrier BG, Watt PJ, Elstein M. Bacteriological colonisation of uterine cavity: role of tailed intrauterine contraceptive device. Br Med J (Clin Res Ed). 1981;282(6271):1189-1191. https://doi.org/10.1136/bmj.282.6271.1189Fardini Y., Chung P., Dumm R., Joshi N., Han Y.P.W. Transmission of diverse oral bacteria to murine placenta: evidence for the oral microbiome as a potential source of intrauterine infection. Infect. Immun. 2010;78(4):1789-1796. https://doi.org/10.1128/IAI.01395-09Fardini Y, Chung P, Dumm R, Joshi N, Han YPW. Transmission of diverse oral bacteria to murine placenta: evidence for the oral microbiome as a potential source of intrauterine infection. Infect Immun. 2010;78(4):1789-1796. https://doi.org/10.1128/IAI.01395-09Han Y.W., Redline R.W., Li M., Yin L., Hill G.B., McCormick T.S. Fusobacterium nucleatum induces premature and term stillbirths in pregnant mice: implication of oral bacteria in preterm birth. Infect. Immun. 2004;72(4):2272-2279. https://doi.org/10.1128/IAI.72.4.2272-2279.2004Han YW, Redline RW, Li M, Yin L, Hill GB, McCormick TS. Fusobacterium nucleatum induces premature and term stillbirths in pregnant mice: implication of oral bacteria in preterm birth. Infect Immun. 2004;72(4):2272-2279. https://doi.org/10.1128/IAI.72.4.2272-2279.2004Swati P., Thomas B., Vahab S.A., Kapaettu S., Kushtagi P. Simultaneous detection of periodontal pathogens in subgingival plaque and placenta of women with hypertension in pregnancy. Arch. Gynecol. Obstet. 2012;285(3):613-619. https://doi.org/10.1007/s00404-011-2012-9Swati P, Thomas B, Vahab SA, Kapaettu S, Kushtagi P. Simultaneous detection of periodontal pathogens in subgingival plaque and placenta of women with hypertension in pregnancy. Arch Gynecol Obstet. 2012;285(3):613-619. https://doi.org/10.1007/s00404-011-2012-9Sola-Leyva A., Andrés-León E., Molina N.M., Terron-Camero L.C., Plaza-Díaz J., Sáez-Lara M.J., Gonzalvo M.C., Sánchez R., Ruíz S., Martínez L., Altmäe S. Mapping the entire functionally active endometrial microbiota. Hum. Reprod. 2021;36(4):1021-1031. https://doi.org/10.1093/humrep/deaa372Sola-Leyva A, Andrés-León E, Molina NM, Terron-Camero LC, Plaza-Díaz J, Sáez-Lara MJ, Gonzalvo MC, Sánchez R, Ruíz S, Martínez L, Altmäe S. Mapping the entire functionally active endometrial microbiota. Hum Reprod. 2021;36(4):1021-31. https://doi.org/10.1093/humrep/deaa372Vanstokstraeten R., Callewaert E., Blotwijk S., Rombauts E., Crombé F., Emmerechts K., Soetens O., Vandoorslaer K., De Geyter D., Allonsius C., Vander Donck L., Blockeel C., Wybo I., Piérard D., Demuyser T., Mackens S. Comparing Vaginal and Endometrial Microbiota Using Culturomics: Proof of Concept. Int. J. Mol. Sci. 2023;24(6):5947. https://doi.org/10.3390/ijms24065947Vanstokstraeten R, Callewaert E, Blotwijk S, Rombauts E, Crombé F, Emmerechts K, Soetens O, Vandoorslaer K, De Geyter D, Allonsius C, Vander Donck L, Blockeel C, Wybo I, Piérard D, Demuyser T, Mackens S. Comparing Vaginal and Endometrial Microbiota Using Culturomics: Proof of Concept. Int J Mol Sci. 2023;24(6):5947. https://doi.org/10.3390/ijms24065947Khan 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://doi.org/10.1016/j.ejogrb.2016.01.040Khan KN, 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://doi.org/10.1016/j.ejogrb.2016.01.040Wessels J.M., Domínguez M.A., Leyland N.A., Agarwal S.K., Foster W.G. Endometrial Microbiota is more diverse in people with endometriosis than symptomatic controls. Sci. Rep. 2021;11:18877. https://doi.org/10.1038/s41598-021-98380-3Wessels JM, Domínguez MA, Leyland NA, Agarwal SK, Foster WG.Endometrial Microbiota is more diverse in people with endometriosis than symptomatic controls. Sci Rep. 2021;11:18877. https://doi.org/10.1038/s41598-021-98380-3Liu Y., Ko E.Y.-L., Wong K.K.-W., Chen X., Cheung W.-C., Law T.S.-M., Chung J.P-W., Tsui S.K.-W., Li T.-C., Chim S.S.-C. Endometrial microbiota in infertile women with and without chronic endometritis as diagnosed using a quantitative and reference range-Based method. Fertil. Steril. 2019;112:707-717. https://doi.org/10.1016/j.fertnstert.2019.05.015Liu Y, Ko EY-L, Wong KK-W, Chen X, Cheung W-C, Law TS-M, Chung JP-W, Tsui SK-W, Li T-C, Chim SS-C. Endometrial microbiota in infertile women with and without chronic endometritis as diagnosed using a quantitative and reference range-Based method. Fertil Steril. 2019;112:707-717. https://doi.org/10.1016/j.fertnstert.2019.05.015Chen P., Chen P., Guo Y., Fang C., Li T. Interaction between chronic endometritis caused endometrial microbiota disorder and endometrial immune environment change in recurrent implantation failure. Front. Immunol. 2021;12:748447. https://doi.org/10.3389/fimmu.2021.748447Chen P, Chen P, Guo Y, Fang C, Li T. Interaction between chronic endometritis caused endometrial microbiota disorder and endometrial immune environment change in recurrent implantation failure. Front Immunol. 2021;12:748447. https://doi.org/10.3389/fimmu.2021.748447Moreno I., Simon C. Relevance of assessing the uterine microbiota in infertility. Fertil. Steril. 2018;110(3):337-343. https://doi.org/10.1016/j.fertnstert.2018.04.041Moreno I, Simon C. Relevance of assessing the uterine microbiota in infertility. Fertil Steril. 2018;110(3):337-343. https://doi.org/10.1016/j.fertnstert.2018.04.041Pelzer E.S., Willner D., Buttini M., Huygens F. A role for the endometrial microbiome in dysfunctional menstrual bleeding. Antonie Van Leeuwenhoek. 2018;111(6):933-943. https://doi.org/10.1007/s10482-017-0992-6Pelzer ES, Willner D, Buttini M, Huygens F. A role for the endometrial microbiome in dysfunctional menstrual bleeding. Antonie Van Leeuwenhoek. 2018;111(6):933-943. https://doi.org/10.1007/s10482-017-0992-6Lu W., He F., Lin Z., Liu S., Tang L., Huang Y., Hu Z. Dysbiosis of the endometrial microbiota and its association with inflammatory cytokines in endometrial cancer. Int. J. Cancer. 2021;148(7):1708-1716. https://doi.org/10.1002/ijc.33428Lu W, He F, Lin Z, Liu S, Tang L, Huang Y, Hu Z. Dysbiosis of the endometrial microbiota and its association with inflammatory cytokines in endometrial cancer. Int J Cancer. 2021;148(7):1708-1716. https://doi.org/10.1002/ijc.33428.

The authors declare that there are no conflicts of interest present.