This research endeavors to elucidate the potential association between urinary microbiota and the prevalence of female pelvic organ prolapse (POP). Leveraging state-of-art metagenomics analysis, we scrutinize the microbial landscape within the urinary tract of individuals with POP, justaposed against a cohort study and summarizing the results of all the correlated papers that approach this subject. Through meticulous study and research, it is aimed to pinpoint distinctive and diverse microbial patterns related with POP development. Findings of the review aspire to shed light on the intricate dynamics between urinary microbiota and female pelvic health, offering nuanced insight into the contributory factors underpinning pelvic organ prolapse. This research not only deepens the understanding of the microbial aspect of POP but also holds promise for informing potential diagnostic and therapeutic avenues in the realm of female pelvic floor disorders.

Keywords: uterine prolapse, pelvic organ prolapse, urinary microbiota, microbiome composition

Uterine prolapse, a distressing condition, profoundly impacts the lives of innumerable women worldwide, often leading to substantial physical and psychological distress. While conventional perspectives have historically implicated anatomical and hormonal factors, recent investigations have redirected attention towards the urinary bladder microbiota as a potential prognostic determinant.¹

Despite the longstanding characterization of the urinary tract as a sterile or aseptic environment, contemporary evidence indicates the presence of a diverse array of heterogeneous bacterial species, regardless of negative findings from clinical cultures. This intricate microbial consortium, known as the urinary microme, beckons further exploration into its potential influence on the functionality of pelvic organs or its contributory role in precipitating urogenital disorders. Moreover, an array of variables, including habits, age, body mass, type of labor, and hormonal status in women, may induce modifications in urinary microbiota composition, potentially culminating in pelvic organ prolapse. Lactobacillus seems still to be recognized as the predominant microbe in the female urinary tract. Urogenital symptoms such as incontinence and conditions like POP are nowadays often linked to reduction in beneficial Lactobacillus species.¹ However, this thesis is not deeply studied. This burgeoning investigative domain has garnered considerable interest, given its capacity to potentially revolutionize our comprehension of uterine prolapse etiology.^1,2 The overarching aim of this comprehensive review is to amalgamate and synthesize existing scholarly works concerning the intricate interplay between urine bladder microbiota composition and the onset of uterine prolapse, thereby elucidating its profound diagnostic and therapeutic ramifications.

The studies considered for this review were identified through a systematic search of major databases, including PubMed, Web of Science, and Google Scholar, up to September 2022. Keywords such as "uterine prolapse", "pelvic organ prolapse", "urinary microbiota," and "microbiome composition" were used to narrow down the selection. Inclusion criteria were set to encompass studies that explored the microbial diversity of urine bladder samples in individuals diagnosed with uterine prolapse, utilizing techniques such as 16S rRNA gene sequencing and metagenomics analysis. Only studies in human population were considered. The research highlighted 66 articles including the above key words. Forty-eight articles were excluded because they concerned microbial communities of other organs, pregnant women or correlation with other medical entities. Aboved methodology is outlined in Table 1.

Table 1 Inclusions and exclusions criteria related methology

The compilation of studies on urogenital symptoms and microbial populations in relation to pelvic organ prolapse (POP) and urinary incontinence reveals diverse findings.

One study focused on mixed urinary incontinence, associating it with pelvic floor therapy, but no clear microbial correlation was identified.

Another study explored urinary urge incontinence post-prolapse surgery and observed a correlation with E. coli, advocating for antibiotic therapy. For stress and urgency urinary incontinence, a group of researchers noted no specified microbe but others observed an increase in Streptococcus anginosus in urgency cases. In addition, another research on urgency urinary incontinence identified Aerococcus spp and Streptococcus spp.

Overactive bladder was associated with Klebsiella spp in one study. Several studies found no clear microbial correlation in overactive bladder and urinary incontinence. However, one study reported a decrease in Lactobacillus spp and an increase in Prevotella spp and Gardnerella spp in urgency urinary incontinence.

Stress urinary incontinence was associated with Atopobium vaginae and Finegoldia magna in another study.

Studies observing a decrease in Lactobacillus spp and an increase in Gardnerella spp in urgency urinary incontinence were also reported. While these findings provide valuable insights into microbial associations, effective interventions to address these factors and alleviate urogenital symptoms, especially in the context of pelvic organ prolapse, remain uncertain.

Moreover, none of the studies shed light on the medication and the pharmacokinetics of the antibiotics that could ameliorate or reverse this situation and these symptoms.

The literature review revealed a growing body of evidence supporting a significant correlation between urine bladder microbiota composition and the incidence of uterine prolapse. Novel observations indicate the presence of septic properties in urine.^3–5 Microbial replication has been identified not only within the superficial bladder cells in the form of intracellular bacterial communities but also highlights the capacity of these microbes to endure and establish a reservoir within the urinary environment.³ Several studies reported alterations in microbial diversity and composition in individuals with urinary incontinence or overactive bladder compared to healthy controls.

Specifically, an increased prevalence of opportunistic pathogens such as Escherichia coli and Staphylococcus aureus was detected in women undergone prolapse surgery. Furthermore, dysbiosis in the bladder microbiota was associated with inflammation and collagen degradation, key factors in the pathogenesis of uterine prolapse.^13,14 Significant distinctions in the microbial populations have been observed between women with and without incontinence, as well as between pre- and postmenopausal women.^15,16

Additionally, certain researchers have incorporated the use of hormonal replacement therapy among peri- and postmenopausal women as a variable in their questionnaires. Furthermore, a separate study underscores the contributory role of the vaginal microbiota in the onset of urinary incontinence. 16S rRNA profiling is a molecular biology technique that plays a crucial role in understanding microbial communities and assessing their diversity in the urinary tract.

Moreover, Expanded Quanntative Urine Culture (EQUC) was used as another tool for the recognition of the variety of the predominant microbiota in thaw female urinary tract.⁶

Table 2 elucidates the crucial involvement of Lactobacillus spp, emphasizing that a reduction in its population may precipitate the onset of diverse urogenital symptoms.^3,7,8,9 This effect is accentuated by an augmented population of Gardnerella spp.^13,17

While all the selected studies establish a link between microbial colonization of the urinary bladder and the presence of urinary incontinence, it is noteworthy that only one investigation explicitly endeavors to correlate pelvic organ prolapse with the female urinary microbiota.^10,11

Consequently, the ability to derive definitive and reliable conclusions is currently constrained by the limited scope of research in this specific domain.

In addition, while antibiotic therapy is discussed, it has not become clear whether conservative treatment could be an effective solution.^1,2

Ultimately, it is essential to note that the requisite intervention to address or ameliorate urinary incontinence and maybe pelvic organ prolapse, exacerbated or triggered by the described microbial reservoir, remains unclear.

The findings presented in this review underscore the pivotal role of urine bladder microbiota in predicting uterine prolapse. The identified microbial signatures offer potential diagnostic biomarkers, opening new avenues for non-invasive screening methods.

Additionally, modulating the urinary microbiota through targeted interventions may hold promise for preventing or managing uterine prolapse.

However, further longitudinal studies and clinical trials are warranted to establish causal relationships and to develop personalized therapeutic approaches.

In light of these discoveries, understanding and manipulating the urine bladder microbiota represents a promising frontier in women's health research, with far-reaching implications for improving the quality of life for individuals affected by uterine prolapse.

None.

None.

All authors declare any financial interest with respect to this manuscript.

1. Komesu YM, Richter HE, Carper B, et al. The urinary microbiome in women with mixed urinary incontinence compared to similarly aged controls. Int Urogynecol J. 2018;29(12):1785–1795.
2. Chen Z, Phan MD, Bates LJ, et al. The urinary microbiome in patients with refractory urge incontinence and recurrent urinary tract infection. Int Urogynecol J. 2018;29(12):1775–1782.
3. Price TK, Lin H, Gao X, et al. Bladder bacterial diversity differs in continent and incontinent women: a cross–sectional study. Am J Obstet Gynecol. 2020;223(5):729.e1–729.e10.
4. Nardos R, Leung ET, Dahl EM, et al. Network–based differences in the vaginal and bladder microbial communities between women with and without urgency urinary incontinence. Front Cell Infect Microbiol. 2022;12:759156.
5. Bae S, Chung H. The urobiome and its role in overactive bladder. Int Neurourol J. 2022;26(3):190–200.
6. Joyce C, Halverson T, Gonzalez C, et al. The urobiomes of adult women with various lower urinary tract symptoms status differ: a re–analysis. Front Cell Infect Microbiol. 2022;12:860408.
7. Javan Balegh Marand A, Baars C, Heesakkers J, et al. Differences in the urinary microbiome of patients with overactive bladder syndrome with and without detrusor overactivity on urodynamic measurements. Life (Basel). 2023;13(5):1199.
8. Schneeweiss J, Koch M, Umek W. The human urinary microbiome and how it relates to urogynecology. Int Urogynecol J. 2016;27:1307–1312.
9. Brubaker L, Wolfe AJ. The female urinary microbiota, urinary health and common urinary disorders. Ann Transl Med. 2017;5(2):34.
10. Brubaker L, Wolfe AJ. Microbiota in 2016: Associating infection and incontinence with the female urinary microbiota. Nat Rev Urol. 2017;14(2):72–74.
11. Curtiss N, Balachandran A, Krska L, et al. A case controlled study examining the bladder microbiome in women with Overactive Bladder (OAB) and healthy controls. Eur J Obstet Gynecol Reprod Biol. 2017;214:31–35.
12. Drake MJ, Morris N, Apostolidis A, et al. The urinary microbiome and its contribution to lower urinary tract symptoms; ICI–RS 2015. Neurourol Urodyn. 2017;36(4):850–853.
13. Fok CS, Gao X, Lin H, et al. Urinary symptoms are associated with certain urinary microbes in urogynecologic surgical patients. Int Urogynecol J. 2018;29(12):1765–1771.
14. Hiergeist A, Gessner A. Clinical implications of the microbiome in urinary tract diseases. Curr Opin Urol. 2017;27(2):93–98.
15. Karstens L, Asquith M, Davin S, et al. Does the urinary microbiome play a role in urgency urinary incontinence and its severity? Front Cell Infect Microbiol. 2016;6:78.
16. Pearce MM, Hilt EE, Rosenfeld AB, et al. The female urinary microbiome: a comparison of women with and without urgency urinary incontinence. mBio. 2014;5(4):e01283–14.
17. Thomas–White KJ, Kliethermes S, Rickey L, et al. Evaluation of the urinary microbiota of women with uncomplicated stress urinary incontinence. Am J Obstet Gynecol. 2017;216(1):55.e1–55.e16.
18. Pearce MM, Zilliox MJ, Rosenfeld AB, et al. The female urinary microbiome in urgency urinary incontinence. Am J Obstet Gynecol. 2015;213(3):347.e1–311.