Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Changes in the Microbiome of Vaginal Fluid after Menopause in Korean Women

  • Kim, Sukyung (Probiotics Microbiome Convergence Center, Soonchunhyang University) ;
  • Seo, Hoonhee (Probiotics Microbiome Convergence Center, Soonchunhyang University) ;
  • Rahim, MD Abdur (Department of Microbiology and Immunology, School of Medicine, Soonchunhyang University) ;
  • Lee, Saebim (Probiotics Microbiome Convergence Center, Soonchunhyang University) ;
  • Kim, Yun-Sook (Department of Obstetrics and Gynecology, Soonchunhyang University Cheonan Hospital) ;
  • Song, Ho-Yeon (Probiotics Microbiome Convergence Center, Soonchunhyang University)
  • Received : 2021.06.09
  • Accepted : 2021.09.01
  • Published : 2021.11.28
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Abstract

Various microorganisms reside in the human vagina; the vaginal microbiome is closely linked to both vaginal and general health, and for this reason, microbiome studies of the vagina are an area of research. In this study, we analyzed the vaginal microbiome of women before and after menopause to further increase our understanding of the vaginal microbiome and its contribution to general health. We did a 16s rRNA gene-based metagenomic analysis on the vaginal fluids of 11 premenopausal and 19 postmenopausal women in Korea. We confirmed that the taxonomic composition was significantly different between the two groups. In postmenopausal women, species richness was significantly decreased, but species diversity was significantly increased. In particular, among the taxonomic components corresponding to all taxon ranks of the vaginal microbiome, a reduction in Lactobacillus taxa after menopause contributed the most to the difference between the two groups. In addition, we confirmed through metabolic analysis that the lactic-acid concentration was also decreased in the vaginal fluid of women after menopause. Our findings on the correlation between menopause and the microbiome could help diagnose menopause and enhance the prevention and treatment diseases related to menopause.

Keywords

Acknowledgement

This research was financially supported by the Ministry of Trade, Industry, and Energy (MOTIE), Korea, under the "Regional Industry-based Organization Support Program" (Ref. No. P0001942) supervised by the Korean Institute for Advancement of Technology (KIAT). This study was also supported by the Soonchunhyang University Research Fund.

References

  1. Marchesi JR, Ravel J. 2015. The vocabulary of microbiome research: a proposal. Microbiome 3: 31. https://doi.org/10.1186/s40168-015-0094-5
  2. Human Microbiome Project C. 2012. A framework for human microbiome research. Nature 486: 215-221. https://doi.org/10.1038/nature11209
  3. Sender R, Fuchs S, Milo R. 2016. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 14: e1002533. https://doi.org/10.1371/journal.pbio.1002533
  4. Grice EA, Segre JA. 2012. The human microbiome: our second genome. Annu. Rev. Genom. Hum. G. 13: 151-170. https://doi.org/10.1146/annurev-genom-090711-163814
  5. Zhao LP. 2010. GENOMICS The tale of our other genome. Nature 465: 879-880. https://doi.org/10.1038/465879a
  6. Qin JJ, Li RQ, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. 2010. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464: 59-U70. https://doi.org/10.1038/nature08821
  7. Lloyd-Price J, Abu-Ali G, Huttenhower C. 2016. The healthy human microbiome. Genome Medicine 8.
  8. Ma B, Forney LJ, Ravel J. 2012. Vaginal microbiome: rethinking health and disease. Annu. Rev. Microbiol. 66: 371-389. https://doi.org/10.1146/annurev-micro-092611-150157
  9. Gupta S, Kakkar V, Bhushan I. 2019. Crosstalk between vaginal microbiome and female health: A review. Microb. Pathog. 136.
  10. Fettweis JM, Serrano MG, Sheth NU, Mayer CM, Glascock AL, Brooks JP, et al. 2012. Species-level classification of the vaginal microbiome. BMC Genomics. 13 Suppl 8: S17.
  11. Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, et al. 2011. Vaginal microbiome of reproductive-age women. Proc. Natl. Acad. Sci. USA 108 Suppl 1: 4680-4687. https://doi.org/10.1073/pnas.1002611107
  12. Srinivasan S, Hoffman NG, Morgan MT, Matsen FA, Fiedler TL, Hall RW, et al. 2012. Bacterial communities in women with bacterial vaginosis: high resolution phylogenetic analyses reveal relationships of microbiota to clinical criteria. PLoS One 7: e37818. https://doi.org/10.1371/journal.pone.0037818
  13. Wang Y, Zhang Y, Zhang Q, Chen H, Feng Y. 2018. Characterization of pelvic and cervical microbiotas from patients with pelvic inflammatory disease. J. Med. Microbiol. 67: 1519-1526. https://doi.org/10.1099/jmm.0.000821
  14. MacIntyre DA, Chandiramani M, Lee YS, Kindinger L, Smith A, Angelopoulos N, et al. 2015. The vaginal microbiome during pregnancy and the postpartum period in a European population. Sci. Rep. 5: 8988. https://doi.org/10.1038/srep08988
  15. Fettweis JM, Brooks JP, Serrano MG, Sheth NU, Girerd PH, Edwards DJ, et al. 2014. Differences in vaginal microbiome in African American women versus women of European ancestry. Microbiology 160: 2272-2282. https://doi.org/10.1099/mic.0.081034-0
  16. Takahashi TA, Johnson KM. 2015. Menopause. Med. Clin. N Am. 99: 521-534. https://doi.org/10.1016/j.mcna.2015.01.006
  17. Nelson HD. 2008. Menopause. Lancet. 371: 760-770. https://doi.org/10.1016/S0140-6736(08)60346-3
  18. Fait T. 2019. Menopause hormone therapy: latest developments and clinical practice. Drugs Context. 8: 212551. https://doi.org/10.7573/dic.212551
  19. Gustafsson RJ, Ahrne S, Jeppsson B, Benoni C, Olsson C, Stjernquist M, et al. 2011. The Lactobacillus flora in vagina and rectum of fertile and postmenopausal healthy Swedish women. BMC Womens Health 11: 17. https://doi.org/10.1186/1472-6874-11-17
  20. Zhang R, Daroczy K, Xiao B, Yu L, Chen R, Liao Q. 2012. Qualitative and semiquantitative analysis of Lactobacillus species in the vaginas of healthy fertile and postmenopausal Chinese women. J. Med. Microbiol. 61: 729-739. https://doi.org/10.1099/jmm.0.038687-0
  21. Pabich WL, Fihn SD, Stamm WE, Scholes D, Boyko EJ, Gupta K. 2003. Prevalence and determinants of vaginal flora alterations in postmenopausal women. J. Infect. Dis. 188: 1054-1058. https://doi.org/10.1086/378203
  22. Bolger AM, Lohse M, Usadel B. 2014. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30: 2114-2120. https://doi.org/10.1093/bioinformatics/btu170
  23. Myers EW, Miller W. 1988. Optimal alignments in linear space. Comput. Appl. Biosci. 4: 11-17.
  24. Wheeler TJ, Eddy SR. 2013. nhmmer: DNA homology search with profile HMMs. Bioinformatics 29: 2487-2489. https://doi.org/10.1093/bioinformatics/btt403
  25. Rognes T, Flouri T, Nichols B, Quince C, Mahe F. 2016. VSEARCH: a versatile open source tool for metagenomics. PeerJ. 4: e2584. https://doi.org/10.7717/peerj.2584
  26. Yoon SH, Ha SM, Kwon S, Lim J, Kim Y, Seo H, et al. 2017. Introducing EzBioCloud: a taxonomically united database of 16S rRNA gene sequences and whole-genome assemblies. Int. J. Syst. Evol. Microbiol. 67: 1613-1617. https://doi.org/10.1099/ijsem.0.001755
  27. Chao A, Lee SM. 1992. Estimating the number of classes via sample coverage. J. Am. Stat. Assoc. 87: 210-217. https://doi.org/10.1080/01621459.1992.10475194
  28. Chao A. 1987. Estimating the population-size for capture recapture data with unequal catchability. Biometrics 43: 783-791. https://doi.org/10.2307/2531532
  29. Burnham KP, Overton WS. 1979. Robust estimation of population-size when capture probabilities vary among animals. Ecology 60: 927-936. https://doi.org/10.2307/1936861
  30. Magurran AE. 2013. Measuring Biological Diversity. Chapter 4 - A index of diversity, "Nonparametric" measures of diversity, pp. 106-109, Wiley-Blackwell|.
  31. Chao A, Shen TJ. 2003. Nonparametric estimation of Shannon's index of diversity when there are unseen species in sample. Environ. Ecol. Stat. 10: 429-443. https://doi.org/10.1023/A:1026096204727
  32. Faith DP. 1992. Conservation evaluation and phylogenetic diversity. Biol. Conserv. 61: 1-10. https://doi.org/10.1016/0006-3207(92)91201-3
  33. Lin JH. 1991. Divergence measures based on the shannon entropy. Ieee T Inform. Theory. 37: 145-151. https://doi.org/10.1109/18.61115
  34. Beals EW. 1984. Bray-curtis ordination - An effective strategy for analysis of multivariate ecological data. Adv. Ecol. Res. 14: 1-55. https://doi.org/10.1016/S0065-2504(08)60168-3
  35. Chen J, Bittinger K, Charlson ES, Hoffmann C, Lewis J, Wu GD, et al. 2012. Associating microbiome composition with environmental covariates using generalized UniFrac distances. Bioinformatics 28: 2106-2113. https://doi.org/10.1093/bioinformatics/bts342
  36. Hamady M, Lozupone C, Knight R. 2010. Fast UniFrac: facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data. ISME J. 4: 17-27. https://doi.org/10.1038/ismej.2009.97
  37. Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, et al. 2011. Metagenomic biomarker discovery and explanation. Genome Biol. 12: R60. https://doi.org/10.1186/gb-2011-12-6-r60
  38. Wallis WHKaWA. 1952. Use of ranks in one-criterion variance analysis. J. Am. Stat. Assoc. 47: 583-621. https://doi.org/10.1080/01621459.1952.10483441
  39. Yuan M, Breitkopf SB, Yang X, Asara JM. 2012. A positive/negative ion-switching, targeted mass spectrometry-based metabolomics platform for bodily fluids, cells, and fresh and fixed tissue. Nat. Protoc. 7: 872-881. https://doi.org/10.1038/nprot.2012.024
  40. Vasquez A, Jakobsson T, Ahrne S, Forsum U, Molin G. 2002. Vaginal lactobacillus flora of healthy Swedish women. J. Clin. Microbiol. 40: 2746-2749. https://doi.org/10.1128/JCM.40.8.2746-2749.2002
  41. 2019. After the Integrative Human Microbiome Project, what's next for the microbiome community? Nature 569: 599.
  42. Cani PD. 2018. Human gut microbiome: hopes, threats and promises. Gut. 67: 1716-1725. https://doi.org/10.1136/gutjnl-2018-316723
  43. Lewis FMT, Bernstein KT, Aral SO. 2017. Vaginal microbiome and its relationship to behavior, sexual health, and sexually transmitted diseases. Obstet. Gynecol. 129: 643-654. https://doi.org/10.1097/AOG.0000000000001932
  44. Brotman RM, Shardell MD, Gajer P, Fadrosh D, Chang K, Silver MI, et al. 2014. Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause 21: 450-458. https://doi.org/10.1097/GME.0b013e3182a4690b
  45. Wang Y, Zhang Y, Zhang Q, Chen H, Feng Y. 2018. Characterization of pelvic and cervical microbiotas from patients with pelvic inflammatory disease. J. Medi. Microbiol. 67: 1519-1526. https://doi.org/10.1099/jmm.0.000821
  46. Tachedjian G, Aldunate M, Bradshaw CS, Cone RA. 2017. The role of lactic acid production by probiotic Lactobacillus species in vaginal health. Res. Microbiol. 168: 782-792. https://doi.org/10.1016/j.resmic.2017.04.001
  47. Lim EY, Lee SY, Shin HS, Lee J, Nam YD, Lee DO, et al. 2020. The Effect of Lactobacillus acidophilus YT1 (MENOLACTO) on improving menopausal symptoms: a randomized, double-blinded, placebo-controlled clinical trial. J. Clin. Med. 9: 2173. https://doi.org/10.3390/jcm9072173
  48. van de Wijgert J. 2017. The vaginal microbiome and sexually transmitted infections are interlinked: consequences for treatment and prevention. PLoS Med. 14: e1002478. https://doi.org/10.1371/journal.pmed.1002478
  49. Eastment MC, McClelland RS. 2018. Vaginal microbiota and susceptibility to HIV. AIDS 32: 687-698. https://doi.org/10.1097/QAD.0000000000001768
  50. Bracewell-Milnes T, Saso S, Nikolaou D, Norman-Taylor J, Johnson M, Thum MY. 2018. Investigating the effect of an abnormal cervico-vaginal and endometrial microbiome on assisted reproductive technologies: A systematic review. Am. J. Reprod. Immunol. 80: e13037. https://doi.org/10.1111/aji.13037