{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:16:04Z","timestamp":1788232564293,"version":"build-2803163510"},"reference-count":50,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:00:00Z","timestamp":1694131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["22-24-00802"],"award-info":[{"award-number":["22-24-00802"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Emerging evidence suggests that the reproductive tract microbiota is a key modulator of local inflammatory and immune pathways throughout pregnancy and may subsequently impact pregnancy outcomes. In this study, our objective was to analyze the cervical and vaginal microbiomes during early pregnancy among three groups: women with healthy ongoing pregnancies, women undergoing dydrogesterone treatment, and those who experienced miscarriages. The experiment involved 51 women at 8\u201311 weeks of gestation. The microbiome was examined using 16S rRNA sequencing on the Ion Torrent PGM platform. Across all groups, Lactobacillus iners was predominant, suggesting that the vaginal community type CST III is common among the majority of participants. Notably, our data highlighted the significant roles of Gardnerella vaginalis and Mycoplasma girerdii in the pathogenesis of early miscarriage. Conversely, L. iners and Bifidobacterium longum have a protective effect in early pregnancy. Moreover, dydrogesterone intake appeared to influence notable differences between the cervical and vaginal microbiomes. Overall, our study enhanced our understanding of the cervical and vaginal microbiome composition in the eastern European population during early pregnancy.<\/jats:p>","DOI":"10.3390\/ijms241813836","type":"journal-article","created":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T07:52:11Z","timestamp":1694159531000},"page":"13836","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Cervical and Vaginal Microbiomes in Early Miscarriages and Ongoing Pregnancy with and without Dydrogesterone Usage"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2076-3868","authenticated-orcid":false,"given":"Mariya","family":"Gryaznova","sequence":"first","affiliation":[{"name":"Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olesya","family":"Kozarenko","sequence":"additional","affiliation":[{"name":"Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia"},{"name":"Antenatal Care Department, Yakovlevo Central District Hospital, 309070 Stroitel, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5820-1804","authenticated-orcid":false,"given":"Yuliya","family":"Smirnova","sequence":"additional","affiliation":[{"name":"Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5881-0845","authenticated-orcid":false,"given":"Inna","family":"Burakova","sequence":"additional","affiliation":[{"name":"Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhail","family":"Syromyatnikov","sequence":"additional","affiliation":[{"name":"Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia"},{"name":"Department of Genetics, Cytology and Bioengineering, Voronezh State University, 394018 Voronezh, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Maslov","sequence":"additional","affiliation":[{"name":"Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia"},{"name":"Department of Genetics, Albert Einstein College of Medicine, New York, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7188-6780","authenticated-orcid":false,"given":"Olga","family":"Lebedeva","sequence":"additional","affiliation":[{"name":"Laboratory of Metagenomics and Food Biotechnology, Voronezh State University of Engineering Technologies, 394036 Voronezh, Russia"},{"name":"Department of Obstetrics and Gynecology, Belgorod State National University, 308015 Belgorod, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,8]]},"reference":[{"key":"ref_1","first-page":"2120","article-title":"Trends in the Incidence, Rate and Treatment of Miscarriage-Nationwide Register-Study in Finland, 1998\u20132016","volume":"34","author":"Linnakaari","year":"2019","journal-title":"Hum. Reprod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1016\/S0140-6736(21)00682-6","article-title":"Miscarriage Matters: The Epidemiological, Physical, Psychological, and Economic Costs of Early Pregnancy Loss","volume":"397","author":"Quenby","year":"2021","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1111\/apm.13288","article-title":"Female Reproductive Tract Microbiome and Early Miscarriages","volume":"131","author":"Lebedeva","year":"2023","journal-title":"APMIS"},{"key":"ref_4","first-page":"433","article-title":"Vaginal Microbiome in Patients with Menstrual Cycle Disorders (Review)","volume":"7","author":"Lebedeva","year":"2021","journal-title":"Res. Results Biomed."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.3389\/fmicb.2017.01162","article-title":"Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity","volume":"8","author":"Gupta","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e00502-20","DOI":"10.1128\/mSystems.00502-20","article-title":"Host Genetic Factors Associated with Vaginal Microbiome Composition in Kenyan Women","volume":"5","author":"Mehta","year":"2020","journal-title":"mSystems"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6079734","DOI":"10.1155\/2019\/6079734","article-title":"Lactobacillus Iners Is Associated with Vaginal Dysbiosis in Healthy Pregnant Women: A Preliminary Study","volume":"2019","author":"Zheng","year":"2019","journal-title":"Biomed. Res. Int."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Smith, B.C., McAndrew, T., Chen, Z., Harari, A., Barris, D.M., Viswanathan, S., Rodriguez, A.C., Castle, P., Herrero, R., and Schiffman, M. (2012). The Cervical Microbiome over 7 Years and a Comparison of Methodologies for Its Characterization. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040425"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s00248-014-0487-1","article-title":"Homogeneity of the Vaginal Microbiome at the Cervix, Posterior Fornix, and Vaginal Canal in Pregnant Chinese Women","volume":"69","author":"Huang","year":"2015","journal-title":"Microb. Ecol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/2049-2618-2-4","article-title":"The Composition and Stability of the Vaginal Microbiota of Normal Pregnant Women Is Different from That of Non-Pregnant Women","volume":"2","author":"Romero","year":"2014","journal-title":"Microbiome"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/s41591-019-0465-8","article-title":"Racioethnic Diversity in the Dynamics of the Vaginal Microbiome during Pregnancy","volume":"25","author":"Serrano","year":"2019","journal-title":"Nat. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Gryaznova, M., Lebedeva, O., Kozarenko, O., Smirnova, Y., Burakova, I., Syromyatnikov, M., Maslov, A., and Popov, V. (2022). Lower Genital Tract Microbiome in Early Pregnancy in the Eastern European Population. Microorganisms, 10.","DOI":"10.3390\/microorganisms10122368"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/s40168-020-00934-6","article-title":"VALENCIA: A Nearest Centroid Classification Method for Vaginal Microbial Communities Based on Composition","volume":"8","author":"France","year":"2020","journal-title":"Microbiome"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"8988","DOI":"10.1038\/srep08988","article-title":"The Vaginal Microbiome during Pregnancy and the Postpartum Period in a European Population","volume":"5","author":"MacIntyre","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"9212","DOI":"10.1038\/s41598-017-07790-9","article-title":"VOGUE Research Group The Vaginal Microbiome of Pregnant Women Is Less Rich and Diverse, with Lower Prevalence of Mollicutes, Compared to Non-Pregnant Women","volume":"7","author":"Freitas","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"132ra52","DOI":"10.1126\/scitranslmed.3003605","article-title":"Temporal Dynamics of the Human Vaginal Microbiota","volume":"4","author":"Gajer","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_17","first-page":"463","article-title":"Lactobacillus Iners-Dominated Vaginal Microbiota in Pregnancy","volume":"84","author":"Mls","year":"2019","journal-title":"Ceska Gynekol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"431","DOI":"10.33073\/pjm-2021-043","article-title":"Can Lactobacillus Spp. Be a Factor Reducing the Risk of Miscarriage?","volume":"70","author":"Kiecka","year":"2021","journal-title":"Pol. J. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40168-016-0223-9","article-title":"The Interaction between Vaginal Microbiota, Cervical Length, and Vaginal Progesterone Treatment for Preterm Birth Risk","volume":"5","author":"Kindinger","year":"2017","journal-title":"Microbiome"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"248","DOI":"10.4014\/jmb.1908.08016","article-title":"Vaginal Microbiota Profiles of Native Korean Women and Associations with High-Risk Pregnancy","volume":"30","author":"Chang","year":"2020","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.rbmo.2022.06.008","article-title":"Female Reproductive Tract Microbiota and Recurrent Pregnancy Loss: A Nested Case-Control Study","volume":"45","author":"Holster","year":"2022","journal-title":"Reprod. Biomed. Online"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"963868","DOI":"10.3389\/fcimb.2022.963868","article-title":"The Role of Probiotics in Vaginal Health","volume":"12","author":"Mei","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1111\/1471-0528.15299","article-title":"Vaginal Microbiome in Early Pregnancy and Subsequent Risk of Spontaneous Preterm Birth: A Case-Control Study","volume":"126","author":"Tabatabaei","year":"2019","journal-title":"BJOG"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"112841","DOI":"10.1016\/j.biopha.2022.112841","article-title":"Potential Pathobionts in Vaginal Microbiota Are Affected by Fish Oil and\/or Probiotics Intervention in Overweight and Obese Pregnant Women","volume":"149","author":"Houttu","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Chen, C., Hao, L., Tian, L., Song, L., Zhang, X., Jie, Z., Tong, X., Xiao, L., Zhang, T., and Jin, X. (2020). Personalized Vagino-Cervical Microbiome Dynamics after Oral Probiotics. bioRxiv.","DOI":"10.1101\/2020.06.16.155929"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kato, S., Nagasawa, T., Uehara, O., Shimizu, S., Sugiyama, N., Hasegawa-Nakamura, K., Noguchi, K., Hatae, M., Kakinoki, H., and Furuichi, Y. (2022). Increase in Bifidobacterium Is a Characteristic of the Difference in the Salivary Microbiota of Pregnant and Non-Pregnant Women. BMC Oral. Health, 22.","DOI":"10.1186\/s12903-022-02293-0"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.32604\/biocell.2003.27.001","article-title":"Interaction of Bifidobacteria with the Gut and Their Influence in the Immune Function","volume":"27","author":"Locascio","year":"2003","journal-title":"Biocell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.anaerobe.2017.05.012","article-title":"Quantification, Isolation and Characterization of Bifidobacterium from the Vaginal Microbiomes of Reproductive Aged Women","volume":"47","author":"Freitas","year":"2017","journal-title":"Anaerobe"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1007\/s00281-020-00817-w","article-title":"The Pregnancy Microbiome and Preterm Birth","volume":"42","author":"Bayar","year":"2020","journal-title":"Semin. Immunopathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"641005","DOI":"10.3389\/fcimb.2021.641005","article-title":"Vaginal Microbiome Composition in Early Pregnancy and Risk of Spontaneous Preterm and Early Term Birth Among African American Women","volume":"11","author":"Dunlop","year":"2021","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"492","DOI":"10.4103\/ijmr.IJMR_350_19","article-title":"Vaginal & Gut Microbiota Diversity in Pregnant Women with Bacterial Vaginosis & Effect of Oral Probiotics: An Exploratory Study","volume":"153","author":"Vasundhara","year":"2021","journal-title":"Indian J. Med. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ajog.2018.12.011","article-title":"Vaginal Dysbiosis and the Risk of Human Papillomavirus and Cervical Cancer: Systematic Review and Meta-Analysis","volume":"221","author":"Brusselaers","year":"2019","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1158\/1940-6207.CAPR-18-0233","article-title":"Evaluation of the Associations Between Cervical Microbiota and HPV Infection, Clearance, and Persistence in Cytologically Normal Women","volume":"12","author":"Ritu","year":"2019","journal-title":"Cancer Prev. Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"So, K.A., Yang, E.J., Kim, N.R., Hong, S.R., Lee, J.-H., Hwang, C.-S., Shim, S.-H., Lee, S.J., and Kim, T.J. (2020). Changes of Vaginal Microbiota during Cervical Carcinogenesis in Women with Human Papillomavirus Infection. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0238705"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jri.2017.03.001","article-title":"Higher Prevalence of Colonization with Gardnerella Vaginalis and Gram-Negative Anaerobes in Patients with Recurrent Miscarriage and Elevated Peripheral Natural Killer Cells","volume":"120","author":"Kuon","year":"2017","journal-title":"J. Reprod. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1093\/cid\/ciu966","article-title":"High Atopobium Vaginae and Gardnerella Vaginalis Vaginal Loads Are Associated with Preterm Birth","volume":"60","author":"Bretelle","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Usyk, M., Zolnik, C.P., Castle, P.E., Porras, C., Herrero, R., Gradissimo, A., Gonzalez, P., Safaeian, M., Schiffman, M., and Burk, R.D. (2020). Cervicovaginal Microbiome and Natural History of HPV in a Longitudinal Study. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008376"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Borgdorff, H., van der Veer, C., van Houdt, R., Alberts, C.J., de Vries, H.J., Bruisten, S.M., Snijder, M.B., Prins, M., Geerlings, S.E., and Schim van der Loeff, M.F. (2017). The Association between Ethnicity and Vaginal Microbiota Composition in Amsterdam, the Netherlands. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0181135"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9061","DOI":"10.1038\/s41598-023-36126-z","article-title":"Microbial Diversity in the Vaginal Microbiota and Its Link to Pregnancy Outcomes","volume":"13","author":"Baud","year":"2023","journal-title":"Sci. Rep."},{"key":"ref_40","first-page":"3307","article-title":"Alteration of Vaginal Microbiota in Patients with Unexplained Recurrent Miscarriage","volume":"17","author":"Zhang","year":"2019","journal-title":"Exp. Ther. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1080\/01443615.2021.1904851","article-title":"Alteration of Vaginal Microbiota in Patients with Recurrent Miscarriage","volume":"42","author":"Jiao","year":"2022","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1515\/jpm-2016-0111","article-title":"Mycoplasma\/Ureaplasma Infection in Pregnancy: To Screen or Not to Screen","volume":"45","author":"Donders","year":"2017","journal-title":"J. Perinat. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1922","DOI":"10.1093\/infdis\/jit100","article-title":"Unique Vaginal Microbiota That Includes an Unknown Mycoplasma-like Organism Is Associated with Trichomonas Vaginalis Infection","volume":"207","author":"Martin","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Fettweis, J.M., Serrano, M.G., Huang, B., Brooks, J.P., Glascock, A.L., Sheth, N.U., Vaginal Microbiome Consortium, Strauss, J.F., Jefferson, K.K., and Buck, G.A. (2014). An Emerging Mycoplasma Associated with Trichomoniasis, Vaginal Infection and Disease. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110943"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/0002-9343(83)91112-9","article-title":"Nonspecific Vaginitis. Diagnostic Criteria and Microbial and Epidemiologic Associations","volume":"74","author":"Amsel","year":"1983","journal-title":"Am. J. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"356.e1","DOI":"10.1016\/j.ajog.2017.05.030","article-title":"Early Pregnancy Vaginal Microbiome Trends and Preterm Birth","volume":"217","author":"Stout","year":"2017","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9966","DOI":"10.1073\/pnas.1705899114","article-title":"Replication and Refinement of a Vaginal Microbial Signature of Preterm Birth in Two Racially Distinct Cohorts of US Women","volume":"114","author":"Callahan","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1038\/s41591-019-0450-2","article-title":"The Vaginal Microbiome and Preterm Birth","volume":"25","author":"Fettweis","year":"2019","journal-title":"Nat. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1067\/S0002-9378(03)00495-2","article-title":"The Potential for Probiotics to Prevent Bacterial Vaginosis and Preterm Labor","volume":"189","author":"Reid","year":"2003","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1136\/ijgc-2018-000032","article-title":"Correlation between the Diversity of Vaginal Microbiota and the Risk of High-Risk Human Papillomavirus Infection","volume":"29","author":"Chao","year":"2019","journal-title":"Int. J. Gynecol. Cancer"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/13836\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:47:15Z","timestamp":1760129235000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/13836"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,8]]},"references-count":50,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["ijms241813836"],"URL":"https:\/\/doi.org\/10.3390\/ijms241813836","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,8]]}}}