IMPORTANCE OF VAGINAL MICROBIOME IN REPRODUCTION
DOI:
https://doi.org/10.47390/3030-3133V3I2Y2025N03Keywords:
pregnancy, ART, implantation failure, recurrent pregnancy loss, missed abortion.Abstract
Vaginal microbiome’s role in reproductive function of women is one of the most important topics nowadays. Thanks to sequencing based technology it is possible to identify variety of microorganisms which was impossible with help of cultural methods. Now both reproductive technology and vaginal microbiome become the most discussed topic in science. This review analysis impact of vaginal microbiome on reproductive outcomes. Usually, non Lactobacillus dominated microbiome is associated with dysbiosis and bacterial vaginosis. These changes in microbiome may result in implantation failure, recurrent pregnancy loss, missed abortion. Thus, analyzing vaginal microbiome and correcting it with antibiotics and probiotics may improve reproductive outcomes.
References
1. Franasiak, J.M.; Scott, R.T., Jr. Reproductive tract microbiome in assisted reproductive technologies. Fertil. Steril. 2015, 104,
1364–1371. [CrossRef]
2. Gagliardi, A.; Totino, V.; Cacciotti, F.; Iebba, V.; Neroni, B.; Bonfiglio, G.; Schippa, S. Rebuilding the Gut Microbiota Ecosystem.
Int. J. Environ. Res. Public Health 2018, 15, 1679. [CrossRef]
3. Garcia-Velasco, J.A.; Budding, D.; Campe, H.; Malfertheiner, S.F.; Hamamah, S.; Santjohanser, C.; Schuppe-Koistinen, I.; Nielsen,
H.S.; Vieira-Silva, S.; Laven, J. The reproductive microbiome—Clinical practice recommendations for fertility specialists. Reprod.
Biomed. Online 2020, 41, 443–453. [CrossRef]
4. Whipps, J.M.; Lewis, K.; Cooke, R.C. Mycoparasitism and plant disease control. In Fungi in Biological Control Systems; Burge,
N.M., Ed.; Manchester University Press: Manchester, UK, 1988; p. 176.
5. Sirota, I.; Zarek, S.M.; Segars, J.H. Potential Influence of the Microbiome on Infertility and Assisted Reproductive Technology.
Semin. Reprod. Med. 2014, 32, 35–42. [CrossRef]
6. Moreno, I.; Codoner, F.M.; Vilella, F.; Valbuena, D.; Martinez-Blanch, J.F.; Jimenez-Almazan, J.; Alonso, R.; Alama, P.; Remohi, J.;
Pellicer, A. Evidence that the endometrial microbiota has an effect on implantation success or failure. Am. J. Obstet. Gynecol. 2016,
215, 684–703. [CrossRef]
7. Aragon, I.M.; Herrera-Imbroda, B.; Queipo-Ortuno, M.I.; Castillo, E.; del Moral, J.S.; Gomez-Millan, J.; Yucel, G.; Lara, M.F. The
Urinary Tract Microbiome in Health and Disease. Eur. Urol. Focus 2018, 4, 128–138. [CrossRef]
8. Baker, J.M.; Chase, D.M.; Herbst-Kralovetz, M.M. Uterine Microbiota: Residents, Tourists, or Invaders? Front. Immunol. 2018,
9, 208. [CrossRef]
9. Moreno, I.; Franasiak, J.M. Endometrial microbiota—New player in town. Fertil. Steril. 2017, 108, 32–39. [CrossRef]
10. The Integrative HMP (iHMP) Research Network Consortium. The Integrative Human Microbiome Project. Nature 2019, 569,
641–648. [CrossRef]
11. Moreno, I.; Simon, C. Deciphering the effect of reproductive tract microbiota on human reproduction. Reprod. Med. Biol. 2019, 18,
40–50. [CrossRef]
12. Hok, T.T.; Loen, L.K.; Tjiat, N.T. Comparative bacteriology of the endocervical mucus. Am. J. Obstet. Gynecol. 1967, 98, 781–783.
[CrossRef]
13. Vitale, S.G.; Loen, L.K.; Tjiat, N.T. The Role of Genital Tract Microbiome in Fertility: A Systematic Review. Int. J. Mol. Sci. 2021,
23, 180. [CrossRef] [PubMed]
14. Wolf, E.A.; Rettig, H.C.; Lupatsii, M.; Schluter, B.; Schafer, K.; Friedrich, D.; Graspeuntner, S.; Rupp, J. Culturomics Approaches
Expand the Diagnostic Accuracy for Sexually Transmitted Infections. Int. J. Mol. Sci. 2021, 22, 10815. [CrossRef] [PubMed]
15. Burton, J.P.; Reid, G. Evaluation of the Bacterial Vaginal Flora of 20 Postmenopausal Women by Direct (Nugent Score) and
Molecular (Polymerase Chain Reaction and Denaturing Gradient Gel Electrophoresis) Techniques. J. Infect. Dis. 2002, 186,
1770–1780. [CrossRef]
16. Pavlova, S.I.; Kilic, A.O.; Kilic, S.S.; So, J.S.; Nader-Macias, M.E.; Simoes, J.A.; Tao, L. Genetic diversity of vaginal lactobacilli from
women in different countries based on 16S rRNA gene sequences. J. Appl. Microbiol. 2002, 92, 451–459. [CrossRef] [PubMed]
17. Yarza, P.; Yilmaz, P.; Pruesse, E.; Glockner, F.O.; Ludwig, W.; Schleifer, K.H.; Whitman, W.B.; Euzeby, J.; Amann, R.; Rossello-Mora,
R. Uniting the classification of cultured and uncultured bacteria and archaea using 16S rRNA gene sequences. Nat. Rev. Microbiol.
2014, 12, 635–645. [CrossRef]
18. Eckburg, P.B.; Bik, E.M.; Bernstein, C.N.; Purdom, E.; Dethlefsen, L.; Sargent, M.; Gill, S.R.; Nelson, K.E.; Relman, D.A. Diversity
of the human intestinal microbial flora. Science 2005, 308, 1635–1638. [CrossRef]
19. Hyman, R.W.; Fukushima, M.; Diamond, L.; Kumm, J.; Giudice, L.C.; Davis, R.W. Microbes on the human vaginal epithelium.
Proc. Natl. Acad. Sci. USA 2005, 102, 7952–7957. [CrossRef] [PubMed]
20. Kumar, J.; Kumar, M.; Gupta, S.; Ahmed, V.; Bhambi, M.; Pandey, R.; Chauhan, N.S. An Improved Methodology to Overcome Key
Issues in Human Fecal Metagenomic DNA Extraction. Genom. Proteom. Bioinform. 2016, 14, 371–378. [CrossRef]
21. Dominguez-Bello, M.G.; Costello, E.K.; Contreras, M.; Magris, M.; Hidalgo, G.; Fierer, N.; Knight, R. Delivery mode shapes the
acquisition and structure of the initial microbiota across multiple body habitats in newborns. Proc. Natl. Acad. Sci. USA 2010, 107,
11971–11975. [CrossRef] [PubMed]
22. Holzer, P.; Farzi, A. Neuropeptides and the microbiota-gut-brain axis. Adv. Exp. Med. Biol. 2014, 817, 195–219.
23. Chang, P.V.; Hao, L.; Offermanns, S.; Medzhitov, R. The microbial metabolite butyrate regulates intestinal macrophage function
via histone deacetylase inhibition. Proc. Natl. Acad. Sci. USA 2014, 111, 2247–2252. [CrossRef] [PubMed]
24. Boskey, E.R.; Cone, R.A.; Whaley, K.J.; Moench, T.R. Origins of vaginal acidity: High D/L lactate ratio is consistent with bacteria
being the primary source. Hum. Reprod. 2001, 16, 1809–1813. [CrossRef] [PubMed]
25. Garcia-Velasco, J.; Menabrito, M.; Catalán, I.B. What fertility specialists should know about the vaginal microbiome: A review.
Reprod. Biomed. Online 2017, 35, 103–112. [CrossRef]
26. O’Hanlon, D.E.; Come, R.A.; Moench, T.R. Vaginal pH measured in vivo: Lactobacilli determine pH and lactic acid concentration.
BMC Microbiol. 2019, 19, 13. [CrossRef] [PubMed]
27. Witkin, S.S.; Linhares, I.M. Why do lactobacilli dominate the human vaginal microbiota? BJOG—Int. J. Obstet. Gynaecol. 2017, 124,
606–611. [CrossRef] [PubMed]
28. O’Hanlon, D.E.; Moench, T.R.; A Cone, R. In vaginal fluid, bacteria associated with bacterial vaginosis can be suppressed with
lactic acid but not hydrogen peroxide. BMC Infect. Dis. 2011, 11, 200. [CrossRef]
29. Ravel, J.; Gajer, P.; Abdo, Z.; Schneider, G.M.; Koenig, S.S.; McCulle, S.L.; Karlebach, S.; Gorle, R.; Russell, J.; Tacket, C.O. Vaginal
microbiome of reproductive-age women. Proc. Natl. Acad. Sci. USA 2011, 108 (Suppl. S1), 4680–4687. [CrossRef]
30. Zhou, X.; Brown, C.J.; Abdo, Z.; Davis, C.C.; Hansmann, M.A.; Joyce, P.; Foster, J.A.; Forney, L.J. Differences in the composition of
vaginal microbial communities found in healthy Caucasian and black women. ISME J. 2007, 1, 121–133. [CrossRef] [PubMed]
31. Gajer, P.; Brotman, R.M.; Bai, G.; Sakamoto, J.; Schutte, U.M.; Zhong, X.; Koenig, S.S.; Fu, L.; Ma, Z.S.; Zhou, X. Temporal dynamics
of the human vaginal microbiota. Sci. Transl. Med. 2012, 4, 132ra52. [CrossRef] [PubMed]
32. Verhelst, R.; Verstraelen, H.; Claeys, G.; Verschraegen, G.; van Simaey, L.; de Ganck, C.; de Backer, E.; Temmerman, M.;
Vaneechoutte, M. Comparison between Gram stain and culture for the characterization of vaginal microflora: Definition of a
distinct grade that resembles grade I microflora and revised categorization of grade I microflora. BMC Microbiol. 2005, 5, 61.
[CrossRef] [PubMed]
33. Zheng, J.; Wittouck, S.; Salvetti, E.; Franz, C.; Harris, H.M.B.; Mattarelli, P.; O’Toole, P.W.; Pot, B.; Vandamme, P.; Walter, J. A
taxonomic note on the genus Lactobacillus: Description of 23 novel genera, emended description of the genus Lactobacillus
Beijerinck 1901, and union of Lactobacillaceae and Leuconostocaceae. Int. J. Syst. Evol. Microbiol. 2020, 70, 2782–2858. [CrossRef]
34. DiGiulio, D.B.; Callahan, B.J.; McMurdie, P.J.; Costello, E.K.; Lyell, D.J.; Robaczewska, A.; Sun, C.L.; Goltsman, D.S.; Wong, R.J.; Shaw, G.; et al. Temporal and spatial variation of the human microbiota during pregnancy. Proc. Natl. Acad. Sci. USA 2015, 112,11060–11065. [CrossRef] [PubMed]
35.Jauniaux, E.; Farquharson, R.G.; Christiansen, O.B.; Exalto, N. Evidence-based guidelines for the investigation and medical treatment of recurrent miscarriage. Hum. Reprod. 2006, 21, 2216–2222. [CrossRef] [PubMed]
36. WHO. WHO: Recommended definitions, terminology and format for statistical tables related to the perinatal period and use of a
new certificate for cause of perinatal deaths. Modifications recommended by FIGO as amended 14 October 1976. Acta Obstet.
Gynecol. Scand. 1977, 56, 247–253.
37. Practice Committee of the American Society for Reproductive Medicine. Definitions of infertility and recurrent pregnancy loss: A
committee opinion. Fertil. Steril. 2020, 113, 533–535. [CrossRef] [PubMed]
38. Fan, T.; Zhong, X.M.; Wei, X.C.; Miao, Z.L.; Luo, S.Y.; Cheng, H.; Xiao, Q. The alteration and potential relationship of vaginal
microbiota and chemokines for unexplained recurrent spontaneous abortion. Medicine 2020, 99, e23558. [CrossRef] [PubMed]
39. Deng, Z.L.; Gottschick, C.; Bhuju, S.; Masur, C.; Abels, C.; Wagner-Dobler, I. Metatranscriptome Analysis of the Vaginal Microbiota
Reveals Potential Mechanisms for Protection against Metronidazole in Bacterial Vaginosis. mSphere 2018, 3, e00262-18. [CrossRef]
[PubMed]
40. Gustin, A.T.; Thurman, A.R.; Chandra, N.; Schifanella, L.; Alcaide, M.; Fichorova, R.; Doncel, G.F.; Gale, M., Jr.; Klatt, N.R.
Recurrent bacterial vaginosis following metronidazole treatment is associated with microbiota richness at diagnosis. Am. J. Obstet.
Gynecol. 2022, 226, 225.e1–225.e15. [CrossRef]
41. Shen, J.; Song, N.; Williams, C.J.; Brown, C.J.; Yan, Z.; Xu, C.; Forney, L.J. Effects of low dose estrogen therapy on the vaginal
microbiomes of women with atrophic vaginitis. Sci. Rep. 2016, 6, 24380. [CrossRef]
42. Plummer, E.L.; Bradshaw, C.S.; Doyle, M.; Fairley, C.K.; Murray, G.L.; Bateson, D.; Masson, L.; Slifirski, J.; Tachedjian, G.; Vodstrcil,
L.A. Lactic acid-containing products for bacterial vaginosis and their impact on the vaginal microbiota: A systematic review.
PLoS ONE 2021, 16, e0246953. [CrossRef]
43. Reichman, O.; Akins, R.; Sobel, J.D. Boric Acid Addition to Suppressive Antimicrobial Therapy for Recurrent Bacterial Vaginosis.
Sex. Transm. Dis. 2009, 36, 732–734. [CrossRef]
44. Bohbot, J.M.; Darai, E.; Bretelle, F.; Brami, G.; Daniel, C.; Cardot, J.M. Efficacy and safety of vaginally administered lyophilized
Lactobacillus crispatus IP 174178 in the prevention of bacterial vaginosis recurrence. J. Gynecol. Obstet. Hum. Reprod. 2018, 47,
81–86. [CrossRef] [PubMed]