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The effect of local estrogen therapy on the urinary microbiome composition of postmenopausal women with and without recurrent urinary tract infections

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Abstract

Introduction and hypothesis

Recurrent urinary tract infections (rUTIs) occur in 2–10% of postmenopausal women. Local estrogen therapy (LET) has been shown to reduce UTIs. This study aimed to compare the urinary microbiome between patients with and without a history of rUTIs and to examine whether treatment with LET influences the diversity and richness of microbiome species in two groups.

Methods

Postmenopausal women with and without rUTIs attending the urogynecology clinic between April 2019 and December 2020 were recruited. Participant baseline characteristics and demographics were recorded. Aseptic transurethral urine samples were collected at recruitment and at 3–6 months following treatment with LET. The V1–V2 and ITS regions of the 16S rRNA gene were sequenced to identify bacteria.

Results

A total of 37 women were recruited, 20 controls and 17 patients with rUTI. During follow-up, symptomatic UTIs occurred in 3/17 (17.6%) and 0/20 in the rUTI group and control group, respectively. Klebsiella aerogenes was present in 80% of rUTI samples and in 53.3% of control samples before LET. Abundance of Finegoldia magna was present in 33.3% of samples before LET, but only in 6.7% after LET. There was no change in relative abundance of lactobacillus species following LET in both groups.

Conclusions

Treatment with vaginal LET altered the local hormonal environment of the urinary bladder and likely protected women from development of rUTI by decreasing the presence of F. magna. To confirm the significance of this bacterial species in rUTI symptomatology, our finding needs to be validated on a larger patient cohort.

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References

  1. Sturdee D, Panay N. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric. 2010;13(6):509–22.

    Article  CAS  Google Scholar 

  2. Nygaard I, Johnson J. Urinary tract infection in elderly women. Am Fam Phys. 1996;53(1):175–82.

    CAS  Google Scholar 

  3. Hayden B, Freeman R, Lee J, Swift S, Cosson M. Deprest. standardization and terminology committees IUGA and ICS, joint IUGA/ICS working group on female terminology. Neurourol Urodyn. 2012;31(4):406–14.

    Article  Google Scholar 

  4. Wolfe A, Toh E, Shibata N, Rong R, Kenton K, FitzGerald M, et al. Evidence of uncultivated bacteria in the adult female bladder. J Clin Microbiol. 2012;50(4):1376–83.

    Article  Google Scholar 

  5. Brubaker L, Wolfe A. The new world of the urinary microbiota in women. Am J Obstet Gynecol. 2015;213(5):644–9.

    Article  Google Scholar 

  6. Pearce M, Hilt E, Rosenfeld A, Zilliox M, Thomas-White K, Fok C. The female urinary microbiome: a comparison of women with and without urgency urinary incontinence. MBio. 2014;5(4):e01283–14.

    Article  CAS  Google Scholar 

  7. Stamm W. Estrogens and urinary-tract infection. J Infect Dis. 2007;195:623–4.

    Article  Google Scholar 

  8. Chen Y, Su T, Lau H. Estrogen for the prevention of recurrent urinary tract infections in postmenopausal women: a meta-analysis of randomized controlled trials. Int Urogynecol J. 2021;32:17–25.

    Article  Google Scholar 

  9. Eriksen B. A randomized, open, parallel-group study on the preventive effect of an estradiol-releasing vaginal ring (Estring) on recurrent urinary tract infections in postmenopausal women. Am J Obstet Gynecol. 1999;180:1072–9.

    Article  CAS  Google Scholar 

  10. Shen J, Song N, William C, Brown C, Yan Z, Xu C. Effects of low dose estrogen therapy on the vaginal microbiomes of women with atrophic vaginitis. Sci Rep. 2016;6:24380.

    Article  CAS  Google Scholar 

  11. Thomas-White K, Taege S, Limeira R, Brubaker L, Mueller E, Wolfe A. Vaginal estrogen therapy is associated with increased Lactobacillus in the urine of postmenopausal women with overactive bladder symptoms. Am J Obstet Gynecol. 2020;223(5):727 e1-727 e11.

    Article  Google Scholar 

  12. The Human Microbiome Project Consortium. A framework for human microbiome research. Nature. 2012;486:215–21.

    Article  Google Scholar 

  13. Edgar R. Search and clustering orders of magnitude faster than BLAST. Bioinformatics. 2010;26(19):2460–1.

    Article  CAS  Google Scholar 

  14. Edgar R. UPARSE: highly accurate OTU sequences from microbial amplicon reads. Nat Methods. 2013;10:996–8.

    Article  CAS  Google Scholar 

  15. Sayers E, Barrett T, Benson D, Bryant S, Canese K, Chetvernin V, et al. Database resources of the national center for biotechnology information. Nucl Acid Res. 2016;4(44):D1 D7-19.

    Google Scholar 

  16. Benson D, Karsch-Mizrachi I, Lipman D, Ostell J, Sayers Z. Genbank. Nucl Acid Res. 2009;37(1):d26–31.

    Article  CAS  Google Scholar 

  17. Chen Z, Phan M, Bates L, Peters K, Mukerjee C, Moore K, et al. The urinary microbiome in patients with refractory urge incontinence and recurrent urinary tract infection. Int Urogynecol J. 2018;29(12):1775–82.

    Article  Google Scholar 

  18. Fok C, Gao X, Lin H, Thomas-White K, Mueller E, Wolfe A, et al. Urinary symptoms are associated with certain urinary microbes in urogynecologic surgical patients. Int Urogynecol J. 2018;29(12):1765–71. https://doi.org/10.1007/s00192-018-3732-1 Int Urogynecol J. 2018;29(12):1765–71.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Wall I, Davies C, Hill K, Wilson M, Stephens P, Harding KG, et al. Potential role of anaerobic cocci in impaired human wound healing. Wound Repair Regen. 2002;10(6):346–53.

    Article  Google Scholar 

  20. Brazier J, Chmelar D, Dubreuil L, Feierl G, Hedberg M, Kalenic S, et al. European surveillance study on antimicrobial susceptibility of grampositive anaerobic cocci. Int J Antimicrob Agents. 2008;31(4):316–20.

    Article  CAS  Google Scholar 

  21. Murdoch D. Gram-positive Anaerobic cocci. Clin Microbiol Rev. 1998;11(1):81–120.

    Article  CAS  Google Scholar 

  22. Stapleton A. The vaginal microbiota and urinary tract infection. Microbiol Spectr. 2016;4(6):10.

    Article  Google Scholar 

  23. Doerflinger S, Throop A, Herbst-Kralovetz M. Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner. J Infect Dis. 2014;209(12):1989–99.

    Article  CAS  Google Scholar 

  24. Chart H. Klebsiella, enterobacter, proteus and other enterobacteria: Pneumonia; urinary tract infection; opportunist infection. Med Microbiol (Eighteenth Edition). 2012;290–7.

  25. Stamm W, McKevitt M, Roberts P, White N. Natural history of recurrent urinary tract infections in women. Rev Infect Dis. 1991;13:77–84.

    Article  CAS  Google Scholar 

  26. Oelschlaeger T, Tall B. Invasion of cultured human epithelial cells by Klebsiella pneumoniaeisolated from the urinary tract. Infect Immun. 1997;65:2950–8.

    Article  CAS  Google Scholar 

  27. Shank E, Kolter R. New developments in microbial interspecies signaling. Curr Opin Microbiol. 2009;12(2):205–14.

    Article  CAS  Google Scholar 

  28. Thomas-White K, Hilt E, Fok C, Pearce M, Mueller E, Kliethermes S, et al. Incontinence medication response relates to the female urinary microbiota. Int Urogynecol J. 2016;27(5):723–33.

    Article  Google Scholar 

  29. Wu P, Chen Y, Zhao J, Zhang G, Chen J, Wang J, et al. Urinary microbiome and psychological factors in women with overactive bladder. Front Cell Infect Microbiol. 2017;7:488.

    Article  Google Scholar 

  30. Cleary M, Grossmann M. Minireview: obesity and breast cancer: the estrogen connection. Endocrinol. 2009;150(6):2537–42.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors thank the study participants and staff of Mount Sinai Hospital’s Urogynecology Clinic for their support. We would also like to thank Microgen personnel Whitney Stanton, Jennifer White and Liz Clines for their assistance with urine processing and microbiome sequencing and Anna Dorogin for technical assistance with urine samples handling.

Funding

International Urogynecology Association 2019 Basic Science Research Grant.

Author information

Authors and Affiliations

Authors

Contributions

B Anglim: project development, patient recruitment, data interpretation, manuscript editing.

C Phillips: data analysis.

O Shynlova: project development, manuscript editing.

M Alarab: project development, patient recruitment, manuscript editing.

Corresponding author

Correspondence to Breffini Anglim.

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Appendix

Appendix

Table 2 Overall test for Hill1 diversity in the recurrent UTI and control groups
Table 3 ANOVA analysis for Hill1 diversity in the control group
Table 4 ANOVA analysis for Hill1 diversity in the recurrent UTI group
Table 5 Overall test for Richness in the recurrent UTI and control groups
Table 6 ANOVA analysis for Richness in the control group
Table 7 ANOVA analysis for Richness in the recurrent UTI group
Table 8 ANOVA analysis for Pielou’s eveness in the control group
Table 9 ANOVA analysis for Pielou’s eveness in the recurrent UTI group
Table 10 PERMANOVA analysis for the recurrent UTI group
Table 11 PERMANOVA analysis for the control group

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Anglim, B., Phillips, C., Shynlova, O. et al. The effect of local estrogen therapy on the urinary microbiome composition of postmenopausal women with and without recurrent urinary tract infections. Int Urogynecol J 33, 2107–2117 (2022). https://doi.org/10.1007/s00192-021-04832-9

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  • DOI: https://doi.org/10.1007/s00192-021-04832-9

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