Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
December-2025 Volume 56 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
December-2025 Volume 56 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Vaginal microbiome and preterm birth: Composition, mechanisms and microbiota‑directed therapies (Review)

  • Authors:
    • Di Cheng
    • Nan Li
    • Qian Sun
    • Kun Wang
    • Fengchun Gao
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250000, P.R. China, Department of Obstetrics, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250000, P.R. China, Department of Clinical Laboratory, Jinan Maternity and Child Care Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250000, P.R. China
    Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 203
    |
    Published online on: September 23, 2025
       https://doi.org/10.3892/ijmm.2025.5644
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Preterm birth (PTB) is a global maternal and neonatal health challenge, affecting ~15 million infants each year. Despite advances in obstetric and neonatal care, PTB‑related morbidity and mortality remain high. Emerging evidence implicates dysbiosis of the vaginal microbiota (VMB) as a key contributor to PTB. A healthy VMB is typically dominated by Lactobacillus spp., which maintain an acidic vaginal environment and inhibit pathogen colonization. Conversely, reduced Lactobacilli abundance alongside overgrowth of anaerobic taxa such as Gardnerella, Atopobium and Mycoplasma is strongly associated with spontaneous PTB and preterm premature rupture of membranes. Excessive proliferation of vaginal pathogens may lead to ascending infection and intra‑amniotic inflammation via activation of host Toll‑like receptor signaling and induction of pro‑inflammatory cytokines IL‑1β, IL‑6 and IL‑8. Moreover, VMB‑derived metabolites such as lactate play important roles in immunomodulation and inflammation. Although antibiotics remain the mainstay for treating bacterial vaginosis, their non‑specific effects often disrupt microbial balance and predispose to recurrence. Recently, probiotic therapies and VMB transplantation have emerged as promising alternative or adjunctive strategies for PTB prevention and management. However, variability in probiotic efficacy and lack of standardized intervention protocols remain significant challenges. The present review examined pregnancy‑associated VMB dynamics, the mechanisms linking dysbiosis to PTB risk and future microbiome‑based intervention strategies, with the aim of informing theoretical and practical approaches to reduce the global burden of preterm birth.
View Figures

Figure 1

Community state types and stability
of the female vaginal microbiota. The vaginal microbiota can be
classified into five CSTs (I-V) based on dominant genera and
species. CST I, II, III and V are each dominated by
Lactobacillus crispatus, L. gasseri, L. iners
and L. jensenii, respectively, whereas CST IV is
characterized by a high diversity of strict and facultative
anaerobes. Vaginal microbial stability correlates positively with
circulating estrogen: during puberty and pregnancy, rising estrogen
levels promote a stable, lactobacilli-dominated community and
acidify vaginal pH. Conversely, estrogen withdrawal leads to
decreased microbial stability and a shift toward more diverse,
non-lactobacilli profiles. CST, community state types; VMB, vaginal
microbiota.

Figure 2

Interplay between pregnancy, glycogen
metabolism and vaginal microbial homeostasis. Elevated estrogen
during pregnancy stimulates epithelial glycogen synthesis, which
vaginal bacterial enzymes hydrolyze into glucose and maltose. These
sugars are fermented by lactobacilli to produce lactic acid,
lowering vaginal pH and inhibiting dysbiosis-associated taxa (such
as Gardnerella vaginalis, Atopobium vaginae and
Prevotella bivia). Lactobacilli also secrete cytolysins that
induce epithelial cell lysis, triggering the release of
hyaluronidase-1 and MMP-8, thereby facilitating glycogen liberation
and further supporting lactobacilli growth. After parturition, the
sudden decline in estrogen precipitates microbial community
restructuring: lactobacilli proportions diminish and
dysbiosis-associated organisms expand. MMP, matrix
metalloproteinase.

Figure 3

Vaginal microbiota-mediated
inflammatory and immune pathways in preterm birth. Pathogen- and
damage-associated molecular patterns (PAMPs and DAMPs) activate
TLRs, which signal via MyD88- and TRIF-dependent pathways to
assemble inflammasomes and release proinflammatory cytokines. TLR
activation also recruits macrophages, whose NF-κB signaling
upregulates both proinflammatory mediators and
contraction-associated genes. Additionally, NF-κB-driven IL-6/STAT3
activation in perivascular stromal cells induces IL-10 production,
maintaining immune homeostasis under inflammatory stress. Elevated
L. iners abundance has been associated with increased
vaginal IgM, C3b, C5/C5a and IL-6; C5a promotes macrophage MMP-9
secretion, driving cervical remodeling. L. iners and G.
vaginalis have both been linked to higher neutrophil counts in
the vagina, which contribute to cervical shortening during labor
and elevate preterm birth risk. PAMPs, pathogen associated
molecular patterns; DAMPs, damage associated molecular patterns;
TLRs, Toll-like receptors; LPS, lipopolysaccharide.
View References

1 

Ohuma EO, Moller AB, Bradley E, Chakwera S, Hussain-Alkhateeb L, Lewin A, Okwaraji YB, Mahanani WR, Johansson EW, Lavin T, et al: National, regional, and global estimates of preterm birth in 2020, with trends from 2010: A systematic analysis. Lancet. 402:1261–1271. 2023. View Article : Google Scholar : PubMed/NCBI

2 

Saigal S and Doyle LW: An overview of mortality and sequelae of preterm birth from infancy to adulthood. Lancet. 371:261–269. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Goldenberg RL, Culhane JF, Iams JD and Romero R: Epidemiology and causes of preterm birth. Lancet. 371:75–84. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Romero R, Gomez-Lopez N, Winters AD, Jung E, Shaman M, Bieda J, Panaitescu B, Pacora P, Erez O, Greenberg JM, et al: Evidence that intra-amniotic infections are often the result of an ascending invasion-a molecular microbiological study. J Perinat Med. 47:915–931. 2019. View Article : Google Scholar : PubMed/NCBI

5 

Witkin SS: The vaginal microbiome, vaginal anti-microbial defence mechanisms and the clinical challenge of reducing infection-related preterm birth. BJOG. 122:213–218. 2015. View Article : Google Scholar

6 

Fox C and Eichelberger K: Maternal microbiome and pregnancy outcomes. Fertil Steril. 104:1358–1363. 2015. View Article : Google Scholar : PubMed/NCBI

7 

Tabatabaei N, Eren AM, Barreiro LB, Yotova V, Dumaine A, Allard C and Fraser WD: Vaginal microbiome in early pregnancy and subsequent risk of spontaneous preterm birth: A case-control study. BJOG. 126:349–358. 2019. View Article : Google Scholar

8 

Liu L, Yin T, Zhang X, Sun L and Yin Y: Temporal and spatial variation of the human placental microbiota during pregnancy. Am J Reprod Immunol. 92:e700232024. View Article : Google Scholar : PubMed/NCBI

9 

Conde-Agudelo A, Papageorghiou AT, Kennedy SH and Villar J: Novel biomarkers for the prediction of the spontaneous preterm birth phenotype: A systematic review and meta-analysis. BJOG. 118:1042–1054. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Meertens LJE, van Montfort P, Scheepers HCJ, van Kuijk SMJ, Aardenburg R, Langenveld J, van Dooren IMA, Zwaan IM, Spaanderman MEA and Smits LJM: Prediction models for the risk of spontaneous preterm birth based on maternal characteristics: A systematic review and independent external validation. Acta Obstet Gynecol Scand. 97:907–920. 2018. View Article : Google Scholar : PubMed/NCBI

11 

Hickey RJ, Zhou X, Pierson JD, Ravel J and Forney LJ: Understanding vaginal microbiome complexity from an ecological perspective. Transl Res. 160:267–282. 2012. View Article : Google Scholar : PubMed/NCBI

12 

Happel AU, Kullin B, Gamieldien H, Wentzel N, Zauchenberger CZ, Jaspan HB, Dabee S, Barnabas SL, Jaumdally SZ, Dietrich J, et al: Exploring potential of vaginal Lactobacillus isolates from South African women for enhancing treatment for bacterial vaginosis. PLoS Pathog. 16:e10085592020. View Article : Google Scholar : PubMed/NCBI

13 

Giannella L, Grelloni C, Quintili D, Fiorelli A, Montironi R, Alia S, Delli Carpini G, Di Giuseppe J, Vignini A and Ciavattini A: Microbiome changes in pregnancy disorders. Antioxidants (Basel). 12:4632023. View Article : Google Scholar : PubMed/NCBI

14 

Bayar E, Bennett PR, Chan D, Sykes L and MacIntyre DA: The pregnancy microbiome and preterm birth. Semin Immunopathol. 42:487–499. 2020. View Article : Google Scholar : PubMed/NCBI

15 

Bachmann NL, Rockett RJ, Timms VJ and Sintchenko V: Advances in clinical sample preparation for identification and characterization of bacterial pathogens using metagenomics. Front Public Health. 6:3632018. View Article : Google Scholar

16 

Sroka-Oleksiak A, Gosiewski T, Pabian W, Gurgul A, Kapusta P, Ludwig-Słomczyńska AH, Wołkow PP and Brzychczy-Włoch M: Next-generation sequencing as a tool to detect vaginal microbiota disturbances during pregnancy. Microorganisms. 8:18132020. View Article : Google Scholar : PubMed/NCBI

17 

Linhares IM, Summers PR, Larsen B, Giraldo PC and Witkin SS: Contemporary perspectives on vaginal pH and lactobacilli. Am J Obstet Gynecol. 204:120.e1–e5. 2011. View Article : Google Scholar

18 

Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO, et al: Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci USA. 108(Suppl 1): S4680–S4687. 2011. View Article : Google Scholar

19 

Blostein F, Gelaye B, Sanchez SE, Williams MA and Foxman B: Vaginal microbiome diversity and preterm birth: Results of a nested case-control study in Peru. Ann Epidemiol. 41:28–34. 2020. View Article : Google Scholar

20 

Stennett CA, Dyer TV, He X, Robinson CK, Ravel J, Ghanem KG and Brotman RM: A cross-sectional pilot study of birth mode and vaginal microbiota in reproductive-age women. PLoS One. 15:e02285742020. View Article : Google Scholar : PubMed/NCBI

21 

Chaban B, Links MG, Jayaprakash TP, Wagner EC, Bourque DK, Lohn Z, Albert AY, van Schalkwyk J, Reid G, Hemmingsen SM, et al: Characterization of the vaginal microbiota of healthy Canadian women through the menstrual cycle. Microbiome. 2:232014. View Article : Google Scholar : PubMed/NCBI

22 

Roy EJ and Mackay R: The concentration of oestrogens in blood during pregnancy. J Obstet Gynaecol Br Emp. 69:13–17. 1962. View Article : Google Scholar : PubMed/NCBI

23 

Ma B, Forney LJ and Ravel J: Vaginal microbiome: Rethinking health and disease. Annu Rev Microbiol. 66:371–389. 2012. View Article : Google Scholar : PubMed/NCBI

24 

van de Wijgert J and Verwijs MC: Lactobacilli-containing vaginal probiotics to cure or prevent bacterial or fungal vaginal dysbiosis: A systematic review and recommendations for future trial designs. BJOG. 127:287–299. 2020. View Article : Google Scholar

25 

Bhandari P, Tingley JP, Palmer DRJ, Abbott DW and Hill JE: Characterization of an α-Glucosidase enzyme conserved in gardnerella spp. isolated from the human vaginal microbiome. J Bacteriol. 203:e00213212021. View Article : Google Scholar

26 

Rosca AS, Castro J, Sousa LGV and Cerca N: Gardnerella and vaginal health: The truth is out there. FEMS Microbiol Rev. 44:73–105. 2020. View Article : Google Scholar

27 

Tachedjian G, Aldunate M, Bradshaw CS and Cone RA: The role of lactic acid production by probiotic Lactobacillus species in vaginal health. Res Microbiol. 168:782–792. 2017. View Article : Google Scholar : PubMed/NCBI

28 

Kaur H, Merchant M, Haque MM and Mande SS: Crosstalk between female gonadal hormones and vaginal microbiota across various phases of women's gynecological lifecycle. Front Microbiol. 11:5512020. View Article : Google Scholar : PubMed/NCBI

29 

Anderson DJ, Marathe J and Pudney J: The structure of the human vaginal stratum corneum and its role in immune defense. Am J Reprod Immunol. 71:618–623. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Shen J, Song N, Williams CJ, Brown CJ, Yan Z, Xu C and Forney LJ: Effects of low dose estrogen therapy on the vaginal microbiomes of women with atrophic vaginitis. Sci Rep. 6:243802016. View Article : Google Scholar : PubMed/NCBI

31 

Cauci S, Driussi S, De Santo D, Penacchioni P, Iannicelli T, Lanzafame P, De Seta F, Quadrifoglio F, de Aloysio D and Guaschino S: Prevalence of bacterial vaginosis and vaginal flora changes in peri- and postmenopausal women. J Clin Microbiol. 40:2147–2152. 2002. View Article : Google Scholar : PubMed/NCBI

32 

Brooks JP, Edwards DJ, Blithe DL, Fettweis JM, Serrano MG, Sheth NU, Strauss JF III, Buck GA and Jefferson KK: Effects of combined oral contraceptives, depot medroxyprogesterone acetate and the levonorgestrel-releasing intrauterine system on the vaginal microbiome. Contraception. 95:405–413. 2017. View Article : Google Scholar

33 

Bradshaw CS, Vodstrcil LA, Hocking JS, Law M, Pirotta M, Garland SM, De Guingand D, Morton AN and Fairley CK: Recurrence of bacterial vaginosis is significantly associated with posttreatment sexual activities and hormonal contraceptive use. Clin Infect Dis. 56:777–786. 2013. View Article : Google Scholar

34 

Garcia-Garcia RM, Arias-Álvarez M, Jordán-Rodríguez D, Rebollar PG, Lorenzo PL, Herranz C and Rodríguez JM: Female reproduction and the microbiota in mammals: Where are we? Theriogenology. 194:144–153. 2022. View Article : Google Scholar : PubMed/NCBI

35 

Fettweis JM, Serrano MG, Brooks JP, Edwards DJ, Girerd PH, Parikh HI, Huang B, Arodz TJ, Edupuganti L, Glascock AL, et al: The vaginal microbiome and preterm birth. Nat Med. 25:1012–1021. 2019. View Article : Google Scholar : PubMed/NCBI

36 

Serrano MG, Parikh HI, Brooks JP, Edwards DJ, Arodz TJ, Edupuganti L, Huang B, Girerd PH, Bokhari YA, Bradley SP, et al: Racioethnic diversity in the dynamics of the vaginal microbiome during pregnancy. Nat Med. 25:1001–1011. 2019. View Article : Google Scholar : PubMed/NCBI

37 

MacIntyre DA, Chandiramani M, Lee YS, Kindinger L, Smith A, Angelopoulos N, Lehne B, Arulkumaran S, Brown R, Teoh TG, et al: The vaginal microbiome during pregnancy and the postpartum period in a European population. Sci Rep. 5:89882015. View Article : Google Scholar : PubMed/NCBI

38 

Zhang X, Zhai Q, Wang J, Ma X, Xing B, Fan H, Gao Z, Zhao F and Liu W: Variation of the vaginal microbiome during and after pregnancy in Chinese women. Genomics Proteomics Bioinformatics. 20:322–333. 2022. View Article : Google Scholar : PubMed/NCBI

39 

Shachar BZ, Mayo JA, Lyell DJ, Baer RJ, Jeliffe-Pawlowski LL, Stevenson DK and Shaw GM: Interpregnancy interval after live birth or pregnancy termination and estimated risk of preterm birth: A retrospective cohort study. BJOG. 123:2009–2017. 2016. View Article : Google Scholar : PubMed/NCBI

40 

McKinney D, House M, Chen A, Muglia L and DeFranco E: The influence of interpregnancy interval on infant mortality. Am J Obstet Gynecol. 216:316.e1–316.e9. 2017. View Article : Google Scholar

41 

Kangatharan C, Labram S and Bhattacharya S: Interpregnancy interval following miscarriage and adverse pregnancy outcomes: Systematic review and meta-analysis. Hum Reprod Update. 23:221–231. 2017.

42 

Bobitt JR and Ledger WJ: Unrecognized amnionitis and prematurity: A preliminary report. J Reprod Med. 19:8–12. 1977.PubMed/NCBI

43 

Andrews WW, Hauth JC, Goldenberg RL, Gomez R, Romero R and Cassell GH: Amniotic fluid interleukin-6: Correlation with upper genital tract microbial colonization and gestational age in women delivered after spontaneous labor versus indicated delivery. Am J Obstet Gynecol. 173:606–612. 1995. View Article : Google Scholar : PubMed/NCBI

44 

Andrews WW, Goldenberg RL, Hauth JC, Cliver SP, Conner M and Goepfert AR: Endometrial microbial colonization and plasma cell endometritis after spontaneous or indicated preterm versus term delivery. Am J Obstet Gynecol. 193:739–745. 2005. View Article : Google Scholar : PubMed/NCBI

45 

Hillier SL, Krohn MA, Cassen E, Easterling TR, Rabe LK and Eschenbach DA: The role of bacterial vaginosis and vaginal bacteria in amniotic fluid infection in women in preterm labor with intact fetal membranes. Clin Infect Dis. 20(Suppl 2): S276–S278. 1995. View Article : Google Scholar : PubMed/NCBI

46 

Leitich H and Kiss H: Asymptomatic bacterial vaginosis and intermediate flora as risk factors for adverse pregnancy outcome. Best Pract Res Clin Obstet Gynaecol. 21:375–390. 2007. View Article : Google Scholar : PubMed/NCBI

47 

Hay PE, Lamont RF, Taylor-Robinson D, Morgan DJ, Ison C and Pearson J: Abnormal bacterial colonisation of the genital tract and subsequent preterm delivery and late miscarriage. BMJ. 308:295–298. 1994. View Article : Google Scholar : PubMed/NCBI

48 

Leitich H, Bodner-Adler B, Brunbauer M, Kaider A, Egarter C and Husslein P: Bacterial vaginosis as a risk factor for preterm delivery: A meta-analysis. Am J Obstet Gynecol. 189:139–147. 2003. View Article : Google Scholar : PubMed/NCBI

49 

Carey JC, Klebanoff MA, Hauth JC, Hillier SL, Thom EA, Ernest JM, Heine RP, Nugent RP, Fischer ML, Leveno KJ, et al: Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National institute of child health and human development network of maternal-fetal medicine units. N Engl J Med. 342:534–540. 2000. View Article : Google Scholar : PubMed/NCBI

50 

Klebanoff MA, Carey JC, Hauth JC, Hillier SL, Nugent RP, Thom EA, Ernest JM, Heine RP, Wapner RJ, Trout W, et al: Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection. N Engl J Med. 345:487–493. 2001. View Article : Google Scholar : PubMed/NCBI

51 

Brocklehurst P, Hannah M and McDonald H: Interventions for treating bacterial vaginosis in pregnancy. Cochrane Database Syst Rev. Jan 20–2000.Epub ahead of print. PubMed/NCBI

52 

Guise JM, Mahon SM, Aickin M, Helfand M, Peipert JF and Westhoff C: Screening for bacterial vaginosis in pregnancy. Am J Prev Med. 20(Suppl 3): S62–S72. 2001. View Article : Google Scholar

53 

Koumans EH, Markowitz LE and Hogan V; CDC BV Working Group: Indications for therapy and treatment recommendations for bacterial vaginosis in nonpregnant and pregnant women: A synthesis of data. Clin Infect Dis. 35(Suppl 2): S152–S172. 2002. View Article : Google Scholar : PubMed/NCBI

54 

Petrova MI, van den Broek M, Balzarini J, Vanderleyden J and Lebeer S: Vaginal microbiota and its role in HIV transmission and infection. FEMS Microbiol Rev. 37:762–792. 2013. View Article : Google Scholar : PubMed/NCBI

55 

Peebles K, Velloza J, Balkus JE, McClelland RS and Barnabas RV: High global burden and costs of bacterial vaginosis: A systematic review and meta-analysis. Sex Transm Dis. 46:304–311. 2019. View Article : Google Scholar : PubMed/NCBI

56 

Onderdonk AB, Delaney ML and Fichorova RN: The human microbiome during bacterial vaginosis. Clin Microbiol Rev. 29:223–238. 2016. View Article : Google Scholar : PubMed/NCBI

57 

Ling Z, Kong J, Liu F, Zhu H, Chen X, Wang Y, Li L, Nelson KE, Xia Y and Xiang C: Molecular analysis of the diversity of vaginal microbiota associated with bacterial vaginosis. BMC Genomics. 11:4882010. View Article : Google Scholar : PubMed/NCBI

58 

Muzny CA and Schwebke JR: Gardnerella vaginalis: Still a prime suspect in the pathogenesis of bacterial vaginosis. Curr Infect Dis Rep. 15:130–135. 2013. View Article : Google Scholar : PubMed/NCBI

59 

Garcia EM, Serrano MG, Edupuganti L, Edwards DJ, Buck GA and Jefferson KK: Sequence comparison of vaginolysin from different gardnerella species. Pathogens. 10:862021. View Article : Google Scholar : PubMed/NCBI

60 

Vaneechoutte M, Guschin A, Van Simaey L, Gansemans Y, Van Nieuwerburgh F and Cools P: Emended description of Gardnerella vaginalis and description of Gardnerella leopoldii sp. nov., Gardnerella piotii sp. nov. and Gardnerella swidsinskii sp. nov., with delineation of 13 genomic species within the genus Gardnerella. Int J Syst Evol Microbiol. 69:679–687. 2019. View Article : Google Scholar : PubMed/NCBI

61 

Ahmed A, Earl J, Retchless A, Hillier SL, Rabe LK, Cherpes TL, Powell E, Janto B, Eutsey R, Hiller NL, et al: Comparative genomic analyses of 17 clinical isolates of Gardnerella vaginalis provide evidence of multiple genetically isolated clades consistent with subspeciation into genovars. J Bacteriol. 194:3922–3937. 2012. View Article : Google Scholar : PubMed/NCBI

62 

Balashov SV, Mordechai E, Adelson ME and Gygax SE: Identification, quantification and subtyping of Gardnerella vaginalis in noncultured clinical vaginal samples by quantitative PCR. J Med Microbiol. 63:162–175. 2014. View Article : Google Scholar

63 

Georgijević A, Cjukić-Ivancević S and Bujko M: Bacterial vaginosis. Epidemiology and risk factors. Srp Arh Celok Lek. 128:29–33. 2000.In Serbian.

64 

van de Wijgert JH, Borgdorff H, Verhelst R, Crucitti T, Francis S, Verstraelen H and Jespers V: The vaginal microbiota: what have we learned after a decade of molecular characterization? PLoS One. 9:e1059982014. View Article : Google Scholar : PubMed/NCBI

65 

France MT, Fu L, Rutt L, Yang H, Humphrys MS, Narina S, Gajer PM, Ma B, Forney LJ and Ravel J: Insight into the ecology of vaginal bacteria through integrative analyses of metagenomic and metatranscriptomic data. Genome Biol. 23:662022. View Article : Google Scholar : PubMed/NCBI

66 

Garcia EM, Kraskauskiene V, Koblinski JE and Jefferson KK: Interaction of gardnerella vaginalis and vaginolysin with the apical versus basolateral face of a three-dimensional model of vaginal epithelium. Infect Immun. 87:e00646–18. 2019. View Article : Google Scholar : PubMed/NCBI

67 

Ragaliauskas T, Plečkaitytė M, Jankunec M, Labanauskas L, Baranauskiene L and Valincius G: Inerolysin and vaginolysin, the cytolysins implicated in vaginal dysbiosis, differently impair molecular integrity of phospholipid membranes. Sci Rep. 9:106062019. View Article : Google Scholar : PubMed/NCBI

68 

Jung HS, Ehlers MM, Lombaard H, Redelinghuys MJ and Kock MM: Etiology of bacterial vaginosis and polymicrobial biofilm formation. Crit Rev Microbiol. 43:651–667. 2017. View Article : Google Scholar : PubMed/NCBI

69 

Swidsinski A, Dörffel Y, Loening-Baucke V, Schilling J and Mendling W: Response of Gardnerella vaginalis biofilm to 5 days of moxifloxacin treatment. FEMS Immunol Med Microbiol. 61:41–46. 2011. View Article : Google Scholar

70 

Castro J, Machado D and Cerca N: Unveiling the role of Gardnerella vaginalis in polymicrobial Bacterial Vaginosis biofilms: The impact of other vaginal pathogens living as neighbors. ISME J. 13:1306–1317. 2019. View Article : Google Scholar : PubMed/NCBI

71 

Jones HE, Harris KA, Azizia M, Bank L, Carpenter B, Hartley JC, Klein N and Peebles D: Differing prevalence and diversity of bacterial species in fetal membranes from very preterm and term labor. PLoS One. 4:e82052009. View Article : Google Scholar : PubMed/NCBI

72 

Suff N, Karda R, Diaz JA, Ng J, Baruteau J, Perocheau D, Tangney M, Taylor PW, Peebles D, Buckley SMK and Waddington SN: Ascending vaginal infection using bioluminescent bacteria evokes intrauterine inflammation, preterm birth, and neonatal brain injury in pregnant mice. Am J Pathol. 188:2164–2176. 2018. View Article : Google Scholar : PubMed/NCBI

73 

Randis TM, Gelber SE, Hooven TA, Abellar RG, Akabas LH, Lewis EL, Walker LB, Byland LM, Nizet V and Ratner AJ: Group B Streptococcus β-hemolysin/cytolysin breaches maternal-fetal barriers to cause preterm birth and intrauterine fetal demise in vivo. J Infect Dis. 210:265–273. 2014. View Article : Google Scholar : PubMed/NCBI

74 

Romero R, Hassan SS, Gajer P, Tarca AL, Fadrosh DW, Bieda J, Chaemsaithong P, Miranda J, Chaiworapongsa T and Ravel J: The vaginal microbiota of pregnant women who subsequently have spontaneous preterm labor and delivery and those with a normal delivery at term. Microbiome. 2:182014. View Article : Google Scholar : PubMed/NCBI

75 

Nelson DB, Shin H, Wu J and Dominguez-Bello MG: The gestational vaginal microbiome and spontaneous preterm birth among Nulliparous African American Women. Am J Perinatol. 33:887–893. 2016. View Article : Google Scholar : PubMed/NCBI

76 

Stout MJ, Zhou Y, Wylie KM, Tarr PI, Macones GA and Tuuli MG: Early pregnancy vaginal microbiome trends and preterm birth. Am J Obstet Gynecol. 217:356.e1–356.e18. 2017. View Article : Google Scholar

77 

Kindinger LM, Bennett PR, Lee YS, Marchesi JR, Smith A, Cacciatore S, Holmes E, Nicholson JK, Teoh TG and MacIntyre DA: The interaction between vaginal microbiota, cervical length, and vaginal progesterone treatment for preterm birth risk. Microbiome. 5:62017. View Article : Google Scholar : PubMed/NCBI

78 

Petrova MI, Reid G, Vaneechoutte M and Lebeer S: Lactobacillus iners: Friend or Foe? Trends Microbiol. 25:182–191. 2017. View Article : Google Scholar

79 

Srinivasan S, Hoffman NG, Morgan MT, Matsen FA, Fiedler TL, Hall RW, Ross FJ, McCoy CO, Bumgarner R, Marrazzo JM and Fredricks DN: Bacterial communities in women with bacterial vaginosis: High resolution phylogenetic analyses reveal relationships of microbiota to clinical criteria. PLoS One. 7:e378182012. View Article : Google Scholar : PubMed/NCBI

80 

Santiago GL, Cools P, Verstraelen H, Trog M, Missine G, El Aila N, Verhelst R, Tency I, Claeys G, Temmerman M and Vaneechoutte M: Longitudinal study of the dynamics of vaginal microflora during two consecutive menstrual cycles. PLoS One. 6:e281802011. View Article : Google Scholar : PubMed/NCBI

81 

Tamrakar R, Yamada T, Furuta I, Cho K, Morikawa M, Yamada H, Sakuragi N and Minakami H: Association between Lactobacillus species and bacterial vaginosis-related bacteria, and bacterial vaginosis scores in pregnant Japanese women. BMC Infect Dis. 7:1282007. View Article : Google Scholar : PubMed/NCBI

82 

Shipitsyna E, Roos A, Datcu R, Hallén A, Fredlund H, Jensen JS, Engstrand L and Unemo M: Composition of the vaginal microbiota in women of reproductive age-sensitive and specific molecular diagnosis of bacterial vaginosis is possible? PLoS One. 8:e606702013. View Article : Google Scholar

83 

Verstraelen H, Verhelst R, Claeys G, De Backer E, Temmerman M and Vaneechoutte M: Longitudinal analysis of the vaginal microflora in pregnancy suggests that L. crispatus promotes the stability of the normal vaginal microflora and that L. gasseri and/or L. iners are more conducive to the occurrence of abnormal vaginal microflora. BMC Microbiol. 9:1162009. View Article : Google Scholar : PubMed/NCBI

84 

Santiago GL, Tency I, Verstraelen H, Verhelst R, Trog M, Temmerman M, Vancoillie L, Decat E, Cools P and Vaneechoutte M: Longitudinal qPCR study of the dynamics of L. crispatus, L. iners, A. vaginae, (sialidase positive) G. vaginalis, and P. bivia in the vagina. PLoS One. 7:e452812012. View Article : Google Scholar : PubMed/NCBI

85 

Macklaim JM, Fernandes AD, Di Bella JM, Hammond JA, Reid G and Gloor GB: Comparative meta-RNA-seq of the vaginal microbiota and differential expression by Lactobacillus iners in health and dysbiosis. Microbiome. 1:122013. View Article : Google Scholar

86 

Gajer P, Brotman RM, Bai G, Sakamoto J, Schütte UM, Zhong X, Koenig SS, Fu L, Ma ZS, Zhou X, et al: Temporal dynamics of the human vaginal microbiota. Sci Transl Med. 4:132ra522012. View Article : Google Scholar : PubMed/NCBI

87 

Petricevic L, Domig KJ, Nierscher FJ, Sandhofer MJ, Fidesser M, Krondorfer I, Husslein P, Kneifel W and Kiss H: Characterisation of the vaginal Lactobacillus microbiota associated with preterm delivery. Sci Rep. 4:51362014. View Article : Google Scholar : PubMed/NCBI

88 

Baldwin EA, Walther-Antonio M, MacLean AM, Gohl DM, Beckman KB, Chen J, White B, Creedon DJ and Chia N: Persistent microbial dysbiosis in preterm premature rupture of membranes from onset until delivery. PeerJ. 3:e13982015. View Article : Google Scholar : PubMed/NCBI

89 

Brown RG, Marchesi JR, Lee YS, Smith A, Lehne B, Kindinger LM, Terzidou V, Holmes E, Nicholson JK, Bennett PR and MacIntyre DA: Vaginal dysbiosis increases risk of preterm fetal membrane rupture, neonatal sepsis and is exacerbated by erythromycin. BMC Med. 16:92018. View Article : Google Scholar : PubMed/NCBI

90 

Brown RG, Al-Memar M, Marchesi JR, Lee YS, Smith A, Chan D, Lewis H, Kindinger L, Terzidou V, Bourne T, et al: Establishment of vaginal microbiota composition in early pregnancy and its association with subsequent preterm prelabor rupture of the fetal membranes. Transl Res. 207:30–43. 2019. View Article : Google Scholar : PubMed/NCBI

91 

DiGiulio DB, Callahan BJ, McMurdie PJ, Costello EK, Lyell DJ, Robaczewska A, Sun CL, Goltsman DS, Wong RJ, Shaw G, et al: Temporal and spatial variation of the human microbiota during pregnancy. Proc Natl Acad Sci USA. 112:11060–11065. 2015. View Article : Google Scholar : PubMed/NCBI

92 

Callahan BJ, DiGiulio DB, Goltsman DSA, Sun CL, Costello EK, Jeganathan P, Biggio JR, Wong RJ, Druzin ML, Shaw GM, et al: Replication and refinement of a vaginal microbial signature of preterm birth in two racially distinct cohorts of US women. Proc Natl Acad Sci USA. 114:9966–9971. 2017. View Article : Google Scholar : PubMed/NCBI

93 

Hyman RW, Fukushima M, Jiang H, Fung E, Rand L, Johnson B, Vo KC, Caughey AB, Hilton JF, Davis RW and Giudice LC: Diversity of the vaginal microbiome correlates with preterm birth. Reprod Sci. 21:32–40. 2014. View Article : Google Scholar :

94 

Elovitz MA, Gajer P, Riis V, Brown AG, Humphrys MS, Holm JB and Ravel J: Cervicovaginal microbiota and local immune response modulate the risk of spontaneous preterm delivery. Nat Commun. 10:13052019. View Article : Google Scholar : PubMed/NCBI

95 

Sun S, Serrano MG, Fettweis JM, Basta P, Rosen E, Ludwig K, Sorgen AA, Blakley IC, Wu MC, Dole N, et al: Race, the vaginal microbiome, and spontaneous preterm birth. mSystems. 7:e00017222022. View Article : Google Scholar : PubMed/NCBI

96 

Kumar M, Murugesan S, Singh P, Saadaoui M, Elhag DA, Terranegra A, Kabeer BSA, Marr AK, Kino T, Brummaier T, et al: Vaginal microbiota and cytokine levels predict preterm delivery in Asian women. Front Cell Infect Microbiol. 11:6396652021. View Article : Google Scholar : PubMed/NCBI

97 

Kindinger LM, MacIntyre DA, Lee YS, Marchesi JR, Smith A, McDonald JA, Terzidou V, Cook JR, Lees C, Israfil-Bayli F, et al: Relationship between vaginal microbial dysbiosis, inflammation, and pregnancy outcomes in cervical cerclage. Sci Transl Med. 8:350ra1022016. View Article : Google Scholar : PubMed/NCBI

98 

Green ES and Arck PC: Pathogenesis of preterm birth: Bidirectional inflammation in mother and fetus. Semin Immunopathol. 42:413–429. 2020. View Article : Google Scholar : PubMed/NCBI

99 

Wahid HH, Dorian CL, Chin PY, Hutchinson MR, Rice KC, Olson DM, Moldenhauer LM and Robertson SA: Toll-Like receptor 4 is an essential upstream regulator of on-time parturition and perinatal viability in mice. Endocrinology. 156:3828–3841. 2015. View Article : Google Scholar : PubMed/NCBI

100 

Chin PY, Dorian CL, Hutchinson MR, Olson DM, Rice KC, Moldenhauer LM and Robertson SA: Novel Toll-like receptor-4 antagonist (+)-naloxone protects mice from inflammation-induced preterm birth. Sci Rep. 6:361122016. View Article : Google Scholar : PubMed/NCBI

101 

Deng W, Yuan J, Cha J, Sun X, Bartos A, Yagita H, Hirota Y and Dey SK: Endothelial cells in the decidual bed are potential therapeutic targets for preterm birth prevention. Cell Rep. 27:1755–1768.e4. 2019. View Article : Google Scholar : PubMed/NCBI

102 

Liassides C, Papadopoulos A, Siristatidis C, Damoraki G, Liassidou A, Chrelias C, Kassanos D and Giamarellos-Bourboulis EJ: Single nucleotide polymorphisms of Toll-like receptor-4 and of autophagy-related gene 16 like-1 gene for predisposition of premature delivery: A prospective study. Medicine (Baltimore). 98:e173132019. View Article : Google Scholar : PubMed/NCBI

103 

Filipovich Y, Lu SJ, Akira S and Hirsch E: The adaptor protein MyD88 is essential for E coli-induced preterm delivery in mice. Am J Obstet Gynecol. 200:93.e1–8. 2009. View Article : Google Scholar : PubMed/NCBI

104 

Montalbano AP, Hawgood S and Mendelson CR: Mice deficient in surfactant protein A (SP-A) and SP-D or in TLR2 manifest delayed parturition and decreased expression of inflammatory and contractile genes. Endocrinology. 154:483–498. 2013. View Article : Google Scholar :

105 

Patni S, Wynen LP, Seager AL, Morgan G, White JO and Thornton CA: Expression and activity of Toll-like receptors 1-9 in the human term placenta and changes associated with labor at term. Biol Reprod. 80:243–248. 2009. View Article : Google Scholar

106 

Krediet TG, Wiertsema SP, Vossers MJ, Hoeks SB, Fleer A, Ruven HJ and Rijkers GT: Toll-like receptor 2 polymorphism is associated with preterm birth. Pediatr Res. 62:474–476. 2007. View Article : Google Scholar : PubMed/NCBI

107 

Lorenz E, Hallman M, Marttila R, Haataja R and Schwartz DA: Association between the Asp299Gly polymorphisms in the Toll-like receptor 4 and premature births in the Finnish population. Pediatr Res. 52:373–376. 2002. View Article : Google Scholar : PubMed/NCBI

108 

Romero R, Xu Y, Plazyo O, Chaemsaithong P, Chaiworapongsa T, Unkel R, Than NG, Chiang PJ, Dong Z, Xu Z, et al: A role for the inflammasome in spontaneous labor at term. Am J Reprod Immunol. 79:e124402018. View Article : Google Scholar

109 

Lindström TM and Bennett PR: The role of nuclear factor kappa B in human labour. Reproduction. 130:569–581. 2005. View Article : Google Scholar : PubMed/NCBI

110 

McCarthy R, Martin-Fairey C, Sojka DK, Herzog ED, Jungheim ES, Stout MJ, Fay JC, Mahendroo M, Reese J, Herington JL, et al: Mouse models of preterm birth: Suggested assessment and reporting guidelines. Biol Reprod. 99:922–937. 2018.PubMed/NCBI

111 

Zhu B, Tao Z, Edupuganti L, Serrano MG and Buck GA: Roles of the microbiota of the female reproductive tract in gynecological and reproductive health. Microbiol Mol Biol Rev. 86:e00181212022. View Article : Google Scholar : PubMed/NCBI

112 

Yudin MH, Landers DV, Meyn L and Hillier SL: Clinical and cervical cytokine response to treatment with oral or vaginal metronidazole for bacterial vaginosis during pregnancy: A randomized trial. Obstet Gynecol. 102:527–534. 2003.PubMed/NCBI

113 

Soto E, Romero R, Richani K, Yoon BH, Chaiworapongsa T, Vaisbuch E, Mittal P, Erez O, Gotsch F, Mazor M and Kusanovic JP: Evidence for complement activation in the amniotic fluid of women with spontaneous preterm labor and intra-amniotic infection. J Matern Fetal Neonatal Med. 22:983–992. 2009. View Article : Google Scholar : PubMed/NCBI

114 

Romero R and Tartakovsky B: The natural interleukin-1 receptor antagonist prevents interleukin-1-induced preterm delivery in mice. Am J Obstet Gynecol. 167:1041–1045. 1992. View Article : Google Scholar : PubMed/NCBI

115 

Nadeau-Vallée M, Quiniou C, Palacios J, Hou X, Erfani A, Madaan A, Sanchez M, Leimert K, Boudreault A, Duhamel F, et al: Novel noncompetitive IL-1 receptor-biased ligand prevents infection- and inflammation-induced preterm birth. J Immunol. 195:3402–3415. 2015. View Article : Google Scholar : PubMed/NCBI

116 

Robertson SA, Christiaens I, Dorian CL, Zaragoza DB, Care AS, Banks AM and Olson DM: Interleukin-6 is an essential determinant of on-time parturition in the mouse. Endocrinology. 151:3996–4006. 2010. View Article : Google Scholar : PubMed/NCBI

117 

Di Simone N, Santamaria Ortiz A, Specchia M, Tersigni C, Villa P, Gasbarrini A, Scambia G and D'Ippolito S: Recent insights on the maternal microbiota: Impact on pregnancy outcomes. Front Immunol. 11:5282022020. View Article : Google Scholar : PubMed/NCBI

118 

Chan D, Bennett PR, Lee YS, Kundu S, Teoh TG, Adan M, Ahmed S, Brown RG, David AL, Lewis HV, et al: Microbial-driven preterm labour involves crosstalk between the innate and adaptive immune response. Nat Commun. 13:9752022. View Article : Google Scholar : PubMed/NCBI

119 

Gonzalez JM, Franzke CW, Yang F, Romero R and Girardi G: Complement activation triggers metalloproteinases release inducing cervical remodeling and preterm birth in mice. Am J Pathol. 179:838–849. 2011. View Article : Google Scholar : PubMed/NCBI

120 

Robertson SA, Skinner RJ and Care AS: Essential role for IL-10 in resistance to lipopolysaccharide-induced preterm labor in mice. J Immunol. 177:4888–4896. 2006. View Article : Google Scholar : PubMed/NCBI

121 

Osman I, Young A, Ledingham MA, Thomson AJ, Jordan F, Greer IA and Norman JE: Leukocyte density and pro-inflammatory cytokine expression in human fetal membranes, decidua, cervix and myometrium before and during labour at term. Mol Hum Reprod. 9:41–45. 2003. View Article : Google Scholar : PubMed/NCBI

122 

Rinaldi SF, Catalano RD, Wade J, Rossi AG and Norman JE: Decidual neutrophil infiltration is not required for preterm birth in a mouse model of infection-induced preterm labor. J Immunol. 192:2315–2325. 2014. View Article : Google Scholar : PubMed/NCBI

123 

Mohd Zaki A, Hadingham A, Flaviani F, Haque Y, Mi JD, Finucane D, Dalla Valle G, Mason AJ, Saqi M, Gibbons DL and Tribe RM: Neutrophils dominate the cervical immune cell population in pregnancy and their transcriptome correlates with the microbial vaginal environment. Front Microbiol. 13:9044512022. View Article : Google Scholar : PubMed/NCBI

124 

Cezar-de-Mello PFT, Ryan S and Fichorova RN: The microRNA cargo of human vaginal extracellular vesicles differentiates parasitic and pathobiont infections from colonization by homeostatic bacteria. Microorganisms. 11:5512023. View Article : Google Scholar : PubMed/NCBI

125 

Zen M, Canova M, Campana C, Bettio S, Nalotto L, Rampudda M, Ramonda R, Iaccarino L and Doria A: The kaleidoscope of glucorticoid effects on immune system. Autoimmun Rev. 10:305–310. 2011. View Article : Google Scholar : PubMed/NCBI

126 

Busillo JM, Azzam KM and Cidlowski JA: Glucocorticoids sensitize the innate immune system through regulation of the NLRP3 inflammasome. J Biol Chem. 286:38703–38713. 2011. View Article : Google Scholar : PubMed/NCBI

127 

Hermoso MA, Matsuguchi T, Smoak K and Cidlowski JA: Glucocorticoids and tumor necrosis factor alpha cooperatively regulate toll-like receptor 2 gene expression. Mol Cell Biol. 24:4743–4756. 2004. View Article : Google Scholar : PubMed/NCBI

128 

Baschant U and Tuckermann J: The role of the glucocorticoid receptor in inflammation and immunity. J Steroid Biochem Mol Biol. 120:69–75. 2010. View Article : Google Scholar : PubMed/NCBI

129 

Franchimont D: Overview of the actions of glucocorticoids on the immune response: A good model to characterize new pathways of immunosuppression for new treatment strategies. Ann NY Acad Sci. 1024:124–137. 2004. View Article : Google Scholar : PubMed/NCBI

130 

Hearps AC, Tyssen D, Srbinovski D, Bayigga L, Diaz DJD, Aldunate M, Cone RA, Gugasyan R, Anderson DJ and Tachedjian G: Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits production of pro-inflammatory mediators associated with HIV acquisition. Mucosal Immunol. 10:1480–1490. 2017. View Article : Google Scholar : PubMed/NCBI

131 

Delgado-Diaz DJ, Tyssen D, Hayward JA, Gugasyan R, Hearps AC and Tachedjian G: Distinct immune responses elicited from cervicovaginal epithelial cells by lactic acid and short chain fatty acids associated with optimal and non-optimal vaginal microbiota. Front Cell Infect Microbiol. 9:4462020. View Article : Google Scholar : PubMed/NCBI

132 

Galdeano CM and Perdigón G: The probiotic bacterium Lactobacillus casei induces activation of the gut mucosal immune system through innate immunity. Clin Vaccine Immunol. 13:219–226. 2006. View Article : Google Scholar : PubMed/NCBI

133 

Rocha-Ramírez LM, Pérez-Solano RA, Castañón-Alonso SL, Moreno Guerrero SS, Ramírez Pacheco A, García Garibay M and Eslava C: Probiotic lactobacillus strains stimulate the inflammatory response and activate human macrophages. J Immunol Res. 2017:46074912017. View Article : Google Scholar : PubMed/NCBI

134 

Anton L, Sierra LJ, DeVine A, Barila G, Heiser L, Brown AG and Elovitz MA: Common cervicovaginal microbial supernatants alter cervical epithelial function: Mechanisms by which lactobacillus crispatus contributes to cervical health. Front Microbiol. 9:21812018. View Article : Google Scholar : PubMed/NCBI

135 

Dizzell S, Nazli A, Reid G and Kaushic C: Protective effect of probiotic bacteria and estrogen in preventing HIV-1-mediated impairment of epithelial barrier integrity in female genital tract. Cells. 8:11202019. View Article : Google Scholar : PubMed/NCBI

136 

Qi W, Li H, Wang C, Li H, Zhang B, Dong M, Fan A, Han C and Xue F: Recent advances in presentation, diagnosis and treatment for mixed vaginitis. Front Cell Infect Microbiol. 11:7597952021. View Article : Google Scholar : PubMed/NCBI

137 

Dong M, Dong Y, Bai J, Li H, Ma X, Li B, Wang C, Li H, Qi W, Wang Y, et al: Interactions between microbiota and cervical epithelial, immune, and mucus barrier. Front Cell Infect Microbiol. 13:11245912023. View Article : Google Scholar : PubMed/NCBI

138 

Schönfeld P and Wojtczak L: Short- and medium-chain fatty acids in energy metabolism: The cellular perspective. J Lipid Res. 57:943–954. 2016. View Article : Google Scholar : PubMed/NCBI

139 

Aldunate M, Srbinovski D, Hearps AC, Latham CF, Ramsland PA, Gugasyan R, Cone RA and Tachedjian G: Antimicrobial and immune modulatory effects of lactic acid and short chain fatty acids produced by vaginal microbiota associated with eubiosis and bacterial vaginosis. Front Physiol. 6:1642015. View Article : Google Scholar : PubMed/NCBI

140 

Amabebe E and Anumba DOC: The vaginal microenvironment: The physiologic role of lactobacilli. Front Med (Lausanne). 5:1812018. View Article : Google Scholar : PubMed/NCBI

141 

Beghini J, Giraldo PC, Linhares IM, Ledger WJ and Witkin SS: Neutrophil gelatinase-associated lipocalin concentration in vaginal fluid: relation to bacterial vaginosis and vulvovaginal candidiasis. Reprod Sci. 22:964–968. 2015. View Article : Google Scholar : PubMed/NCBI

142 

Stafford GP, Parker JL, Amabebe E, Kistler J, Reynolds S, Stern V, Paley M and Anumba DOC: spontaneous preterm birth is associated with differential expression of vaginal metabolites by lactobacilli-dominated microflora. Front Physiol. 8:6152017. View Article : Google Scholar : PubMed/NCBI

143 

Amabebe E and Anumba DOC: A combination of cervicovaginal fluid glutamate, acetate and D-Lactate identified asymptomatic low-risk women destined to deliver preterm: A prospective cohort study. Reprod Sci. 29:915–922. 2022. View Article : Google Scholar

144 

Ghartey J, Bastek JA, Brown AG, Anglim L and Elovitz MA: Women with preterm birth have a distinct cervicovaginal metabolome. Am J Obstet Gynecol. 212:776.e1–776.e12. 2015. View Article : Google Scholar : PubMed/NCBI

145 

Srinivasan S, Morgan MT, Fiedler TL, Djukovic D, Hoffman NG, Raftery D, Marrazzo JM and Fredricks DN: Metabolic signatures of bacterial vaginosis. mBio. 6:e002042015. View Article : Google Scholar : PubMed/NCBI

146 

Menon R, Jones J, Gunst PR, Kacerovsky M, Fortunato SJ, Saade GR and Basraon S: Amniotic fluid metabolomic analysis in spontaneous preterm birth. Reprod Sci. 21:791–803. 2014. View Article : Google Scholar : PubMed/NCBI

147 

Lizewska B, Teul J, Kuc P, Lemancewicz A, Charkiewicz K, Goscik J, Kacerovsky M, Menon R, Miltyk W and Laudanski P: Maternal plasma metabolomic profiles in spontaneous preterm birth: Preliminary results. Mediators Inflamm. 2018:93628202018. View Article : Google Scholar : PubMed/NCBI

148 

Smith DD and Rood KM: Intrahepatic cholestasis of pregnancy. Clin Obstet Gynecol. 63:134–151. 2020. View Article : Google Scholar

149 

Tuckey RC: Progesterone synthesis by the human placenta. Placenta. 26:273–281. 2005. View Article : Google Scholar : PubMed/NCBI

150 

Wilks M, Wiggins R, Whiley A, Hennessy E, Warwick S, Porter H, Corfield A and Millar M: Identification and H(2) O(2) production of vaginal lactobacilli from pregnant women at high risk of preterm birth and relation with outcome. J Clin Microbiol. 42:713–717. 2004. View Article : Google Scholar : PubMed/NCBI

151 

O'Hanlon DE, Moench TR and Cone RA: In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with lactic acid but not hydrogen peroxide. BMC Infect Dis. 11:2002011. View Article : Google Scholar : PubMed/NCBI

152 

Mitchell C, Fredricks D, Agnew K and Hitti J: Hydrogen peroxide-producing lactobacilli are associated with lower levels of vaginal interleukin-1β, independent of bacterial vaginosis. Sex Transm Dis. 42:358–363. 2015. View Article : Google Scholar : PubMed/NCBI

153 

Hemmerling A, Harrison W, Schroeder A, Park J, Korn A, Shiboski S, Foster-Rosales A and Cohen CR: Phase 2a study assessing colonization efficiency, safety, and acceptability of Lactobacillus crispatus CTV-05 in women with bacterial vaginosis. Sex Transm Dis. 37:745–750. 2010. View Article : Google Scholar : PubMed/NCBI

154 

Mayer BT, Srinivasan S, Fiedler TL, Marrazzo JM, Fredricks DN and Schiffer JT: Rapid and profound shifts in the vaginal microbiota following antibiotic treatment for bacterial vaginosis. J Infect Dis. 212:793–802. 2015. View Article : Google Scholar : PubMed/NCBI

155 

Bayar E, MacIntyre DA, Sykes L, Mountain K, Parks TP, Lee PP and Bennett PR: Safety, tolerability, and acceptability of Lactobacillus crispatus CTV-05 (LACTIN-V) in pregnant women at high-risk of preterm birth. Benef Microbes. 14:45–56. 2023. View Article : Google Scholar : PubMed/NCBI

156 

Tomusiak A, Strus M, Heczko PB, Adamski P, Stefański G, Mikołajczyk-Cichońska A and Suda-Szczurek M: Efficacy and safety of a vaginal medicinal product containing three strains of probiotic bacteria: A multicenter, randomized, double-blind, and placebo-controlled trial. Drug Des Devel Ther. 9:5345–5354. 2015. View Article : Google Scholar : PubMed/NCBI

157 

Vasundhara D, Raju VN, Hemalatha R, Nagpal R and Kumar M: Vaginal & gut microbiota diversity in pregnant women with bacterial vaginosis & effect of oral probiotics: An exploratory study. Indian J Med Res. 153:492–502. 2021. View Article : Google Scholar : PubMed/NCBI

158 

Reid G, Charbonneau D, Erb J, Kochanowski B, Beuerman D, Poehner R and Bruce AW: Oral use of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal flora: Randomized, placebo-controlled trial in 64 healthy women. FEMS Immunol Med Microbiol. 35:131–134. 2003. View Article : Google Scholar : PubMed/NCBI

159 

Ho M, Chang YY, Chang WC, Lin HC, Wang MH, Lin WC and Chiu TH: Oral Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 to reduce Group B Streptococcus colonization in pregnant women: A randomized controlled trial. Taiwan J Obstet Gynecol. 55:515–518. 2016. View Article : Google Scholar : PubMed/NCBI

160 

Anukam KC, Osazuwa E, Osemene GI, Ehigiagbe F, Bruce AW and Reid G: Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis. Microbes Infect. 8:2772–2776. 2006. View Article : Google Scholar : PubMed/NCBI

161 

Hemalatha R, Mastromarino P, Ramalaxmi BA, Balakrishna NV and Sesikeran B: Effectiveness of vaginal tablets containing lactobacilli versus pH tablets on vaginal health and inflammatory cytokines: A randomized, double-blind study. Eur J Clin Microbiol Infect Dis. 31:3097–3105. 2012. View Article : Google Scholar : PubMed/NCBI

162 

Husain S, Allotey J, Drymoussi Z, Wilks M, Fernandez-Felix BM, Whiley A, Dodds J, Thangaratinam S, McCourt C, Prosdocimi EM, et al: Effects of oral probiotic supplements on vaginal microbiota during pregnancy: A randomised, double-blind, placebo-controlled trial with microbiome analysis. BJOG. 127:275–284. 2020. View Article : Google Scholar

163 

Gille C, Böer B, Marschal M, Urschitz MS, Heinecke V, Hund V, Speidel S, Tarnow I, Mylonas I, Franz A, et al: Effect of probiotics on vaginal health in pregnancy. EFFPRO, a randomized controlled trial. Am J Obstet Gynecol. 215:608.e1–608.e7. 2016. View Article : Google Scholar

164 

Govinden G, Parker JL, Naylor KL, Frey AM, Anumba DOC and Stafford GP: Inhibition of sialidase activity and cellular invasion by the bacterial vaginosis pathogen Gardnerella vaginalis. Arch Microbiol. 200:1129–1133. 2018. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Cheng D, Li N, Sun Q, Wang K and Gao F: Vaginal microbiome and preterm birth: Composition, mechanisms and microbiota‑directed therapies (Review). Int J Mol Med 56: 203, 2025.
APA
Cheng, D., Li, N., Sun, Q., Wang, K., & Gao, F. (2025). Vaginal microbiome and preterm birth: Composition, mechanisms and microbiota‑directed therapies (Review). International Journal of Molecular Medicine, 56, 203. https://doi.org/10.3892/ijmm.2025.5644
MLA
Cheng, D., Li, N., Sun, Q., Wang, K., Gao, F."Vaginal microbiome and preterm birth: Composition, mechanisms and microbiota‑directed therapies (Review)". International Journal of Molecular Medicine 56.6 (2025): 203.
Chicago
Cheng, D., Li, N., Sun, Q., Wang, K., Gao, F."Vaginal microbiome and preterm birth: Composition, mechanisms and microbiota‑directed therapies (Review)". International Journal of Molecular Medicine 56, no. 6 (2025): 203. https://doi.org/10.3892/ijmm.2025.5644
Copy and paste a formatted citation
x
Spandidos Publications style
Cheng D, Li N, Sun Q, Wang K and Gao F: Vaginal microbiome and preterm birth: Composition, mechanisms and microbiota‑directed therapies (Review). Int J Mol Med 56: 203, 2025.
APA
Cheng, D., Li, N., Sun, Q., Wang, K., & Gao, F. (2025). Vaginal microbiome and preterm birth: Composition, mechanisms and microbiota‑directed therapies (Review). International Journal of Molecular Medicine, 56, 203. https://doi.org/10.3892/ijmm.2025.5644
MLA
Cheng, D., Li, N., Sun, Q., Wang, K., Gao, F."Vaginal microbiome and preterm birth: Composition, mechanisms and microbiota‑directed therapies (Review)". International Journal of Molecular Medicine 56.6 (2025): 203.
Chicago
Cheng, D., Li, N., Sun, Q., Wang, K., Gao, F."Vaginal microbiome and preterm birth: Composition, mechanisms and microbiota‑directed therapies (Review)". International Journal of Molecular Medicine 56, no. 6 (2025): 203. https://doi.org/10.3892/ijmm.2025.5644
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team