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.
Similar content being viewed by others
References
Sturdee D, Panay N. Recommendations for the management of postmenopausal vaginal atrophy. Climacteric. 2010;13(6):509–22.
Nygaard I, Johnson J. Urinary tract infection in elderly women. Am Fam Phys. 1996;53(1):175–82.
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.
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.
Brubaker L, Wolfe A. The new world of the urinary microbiota in women. Am J Obstet Gynecol. 2015;213(5):644–9.
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.
Stamm W. Estrogens and urinary-tract infection. J Infect Dis. 2007;195:623–4.
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.
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.
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.
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.
The Human Microbiome Project Consortium. A framework for human microbiome research. Nature. 2012;486:215–21.
Edgar R. Search and clustering orders of magnitude faster than BLAST. Bioinformatics. 2010;26(19):2460–1.
Edgar R. UPARSE: highly accurate OTU sequences from microbial amplicon reads. Nat Methods. 2013;10:996–8.
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.
Benson D, Karsch-Mizrachi I, Lipman D, Ostell J, Sayers Z. Genbank. Nucl Acid Res. 2009;37(1):d26–31.
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.
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.
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.
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.
Murdoch D. Gram-positive Anaerobic cocci. Clin Microbiol Rev. 1998;11(1):81–120.
Stapleton A. The vaginal microbiota and urinary tract infection. Microbiol Spectr. 2016;4(6):10.
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.
Chart H. Klebsiella, enterobacter, proteus and other enterobacteria: Pneumonia; urinary tract infection; opportunist infection. Med Microbiol (Eighteenth Edition). 2012;290–7.
Stamm W, McKevitt M, Roberts P, White N. Natural history of recurrent urinary tract infections in women. Rev Infect Dis. 1991;13:77–84.
Oelschlaeger T, Tall B. Invasion of cultured human epithelial cells by Klebsiella pneumoniaeisolated from the urinary tract. Infect Immun. 1997;65:2950–8.
Shank E, Kolter R. New developments in microbial interspecies signaling. Curr Opin Microbiol. 2009;12(2):205–14.
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.
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.
Cleary M, Grossmann M. Minireview: obesity and breast cancer: the estrogen connection. Endocrinol. 2009;150(6):2537–42.
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
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
Ethics declarations
Conflicts of interest
None.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Appendix
Appendix
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00192-021-04832-9