gms | German Medical Science

32. Kongress der Deutschen Kontinenz Gesellschaft

Deutsche Kontinenz Gesellschaft e. V.

05. - 06.11.2021, online

The female urinary microbiome and its correlation with urgency urinary incontinence

Meeting Abstract

Deutsche Kontinenz Gesellschaft e.V.. 32. Kongress der Deutschen Kontinenz Gesellschaft. sine loco [digital], 05.-06.11.2021. Düsseldorf: German Medical Science GMS Publishing House; 2021. Doc01

doi: 10.3205/21dkg01, urn:nbn:de:0183-21dkg013

Published: November 4, 2021

© 2021 Javan et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.


Outline

Text

Introduction: The term “Microbiota” refers to a collection or community of microbes. The term “Microbiome” refers to the full collection of genes of all microbes [1], [2]. Opposite to the common misuse of these two terms they carry distinct meanings which enforces the careful use of the two.

Microbial populations are present in the human body, residing in different organs such as the gastrointestinal, the skin, upper respiratory and the genital tracts [1]. There are different elements contributing to shape characteristics of the microbiome communities in body, which include: age, gender, hormonal status, body mass index, diet, environment, host genetics and early microbial exposure [3], [4], [5], [6].

Furthermore, for bacterial populations, being beneficial and pathogenic is a relative concept depending on the individual’s microbiome characteristics [7], [8].

Maintenance of a normal microbiome is thought to be essential in the intestine and probably also in the urinary bladder [9].

Urine of healthy individuals has for long been considered to be sterile. Improved bacteria detection methods, however, have debunked this assumption. Recent discoveries have proven the bladder to contain microbiomes, not perceivable under standard conditions

The urinary microbiome is an exciting and fresh notion which has captivated the fascination of medical research. The little while, beginning from its revelation, has been fruitful, producing multiple publications by a variety of research teams, who have thus far revised our vision towards the role of bacteria in the urinary tract and the very perception of genitourinary health.

Figure 1 [Fig. 1]

Methods: Our objective in this paper is to present an overview of all published literature regarding the relationship between the urinary microbiota and functional disorders of the genitourinary tract, including urgency urinary incontinence, through a review. These studies were gathered through PubMed, Medline and Cochrane databases.

All the urine is collected using a transurethral catheter in order to elude the urine from bacterial contamination from the external tissues and in order to determine the resident microbial, the bacterial 16S rRNA is amplified through PCR and the NGS sequencing is performed through illumina MiSeq.

Results: Commonly interpreted as the “hidden condition”, it is a diagnosis of exclusion focused on ruling out other symptoms. Urine culture is used to rule out infection in patients with OAB symptoms. The aetiology of OAB is rather vague and so those not in the realm of neuromuscular dysfunction are counselled. A possibility already put forward, is the impact of microbes which inhabit the lower urinary tract (urinary microbiota) on OAB symptoms [10].

Considering the unveiling of urinary microbiome, studies using the 16S RNA gene sequencing have been conducted to discover if bacteria, not discovered prior in the urinary tract, could plainly or circuitously, contribute or be a result of OAB [4]. This method, along with disbursed quantitative urine culture technique to compare catheter urine from women with or without urgency urinary incontinence (UUI), argue the possibility that significant contrasts remain in the urinary microbiome of women with and without UUI, which do have an strong insunuation in the prevention, diagnosis and treatment of UUI. In subjects not suffering from UUI more Lactobacillus spp. were found compared to cohort without UUI, whereas in UUI patients more Gardnerella spp. were found [4].

From these study results, it may be concluded that Lactobacillus has a possible preventive role, whereas Gardnerella has shown a possible causative role patients affected by OAB. However, it is under debate whether the use of antibiotics in treating Gardnerella has any effect on lower urinary tract function, or that Gardnerella spp. role in urine tract function is more complex. For instance, bacteriophages (bacterial viruses) may also play a role [4]. Furthermore, the bacterial genera Actinobaculum spp., Actinomyces spp., Aerococcus spp. Arthrobacter spp., Corynebacterium spp., Oligella spp., Staphylococcus spp. and Streptococcus spp. were sheltered at a higher frequency in the UUI cohort. Lactobacillus gasseri was discovered to be related with UUI, whilst Lactobacillus crispatus was affiliated with women who had no LUTS [4].

A study using 16S rRNA gene sequencing on catheter urine samples of untreated women with UUI has shown that more than one-half of the patients’ samples tested positive for bacterial DNA and the positive outcomes were associated with younger age, higher Body Mass Index (BMI), more austere UUI, better response to treatment and lower susceptibility to UTIs [11]. Furthermore, Lactobacillus spp. were unveiled in the prevailing of the sequence positive samples. The second most continually detected genus was Gardnerella spp. [11]. These discoveries bring about the possibility that some bacteria may have a protective application in the bladder as they possess so in other human biological niches.

Data 16S rRNA Gene sequencing in urine of OAB patients and controls unveiled a consequential diversity in the classification of bacteria detected among the subjects, e.g. seven genera including Proteus and Aerococcus were increased and 13 genera including Lactobacillus and Prevotella were decreased in the OAB patients in comparison to controls [10], [12]. Other researchers have made the proposition that an increase in OAB symptom severity is associated with a reduction in microbial miscellany [13] while in another study have demonstrated a relation among OAB symptoms and pyuria, with noteworthy urgency correlating with pyuria and epithelial cell shedding where routine urine cultures were not able to discern OAB subjects from controls [14].

More recently, scientists have recounted the urinary microbiome of a female OAB subject with the use of high throughput 16 rDNA pyrosequencing on successive urine samples, one year apart. In the first specimen, a standard urine culture was positive for Streptococcus. The subject had undergone antibiotics treatment and, a year later, the standard urine culture was negative. However, urinary symptoms were still perceivable. The existence of fastidious and anaerobic bacteria had come to be known by 16S rDNA analysis of both urine samples, with insignificant variations made to the microbial diversity occurring within one year. Thus, the correlatively sustained microbiome and the persistence of urinary symptoms, not considering antibiotics treatment, indicate a probable association among OAB and urinary microbiota [15]. On the other hand, a latter study concluded that responders were more plausible to have less and less diverse bacteria, through the study of women’s urine with UUI and the relation between urinary microbiota and their reaction to incontinence medication [16].

Taking all the available studies into account, the implication may be made that Lactobacillus plays a preventive role. These combined discoveries could have significant impacts on the future diagnosis, treatment and prevention of UUI.

Table 1 [Tab. 1]

Conclusion: The studies published show that Lactobassilus in patients suffering from OAB had increased in comparison to the subjects without the condition [10], [11], [16], [17] in addition we found that in only one study a decrease in Lactobacillus was observed with an increase of Gardnerella spp. [4]. In another study in patients suffering from OAB, an increase in Streptococcus compared to healthy subjects was observed [15].

The urinary microbiome is an exciting and fresh notion which has overwhelmingly captivated the fascination of medical research. The little while, beginning from its revelation, has been fruitful, producing mountainous publications by a variety of research teams, who have thus far revised our vision towards the role of bacteria in the urinary tract and the very perception of genitourinary health.

Furthermore a better understanding of urinary microbiota could provide a biomarker for a better diagnosis and categorizing the patient with idiopathic urgency incontinence. Furthermore altering the microbiota could provide exciting new therapeutic possibilities.


References

1.
Turnbaugh PJ, et al. The human microbiome project. Nature. 2007;449(7164):804-10.
2.
Wolfe AJ, Brubaker L. "Sterile Urine" and the Presence of Bacteria. Eur Urol. 2015;68(2):173-4.
3.
Drake MJ, et al. The urinary microbiome and its contribution to lower urinary tract symptoms; ICI-RS 2015. Neurourol Urodyn. 2017;36(4):850-853.
4.
Pearce MM, et al. The female urinary microbiome: a comparison of women with and without urgency urinary incontinence. mBio. 2014;5(4):e01283-14.
5.
Thomas-White KJ, 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.
6.
Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207-14.
7.
Brubaker L, Wolfe A. The urinary microbiota: a paradigm shift for bladder disorders? Curr Opin Obstet Gynecol. 2016;28(5):407-12.
8.
A framework for human microbiome research. Nature. 2012;486(7402):215-21.
9.
Marchesi JR, et al. The gut microbiota and host health: a new clinical frontier. Gut. 2016;65(2):330-9.
10.
Hilt EE et al. Urine is not sterile: use of enhanced urine culture techniques to detect resident bacterial flora in the adult female bladder. J Clin Microbiol. 2014;52(3):871-6.
11.
Pearce MM, et al. The female urinary microbiome in urgency urinary incontinence. Am J Obstet Gynecol. 2015;213(3):347.e1-11.
12.
Curtiss N, 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.
13.
Karstens L, et al. Does the Urinary Microbiome Play a Role in Urgency Urinary Incontinence and Its Severity? Front Cell Infect Microbiol. 2016;6:78.
14.
Gill K, et al. A blinded observational cohort study of the microbiological ecology associated with pyuria and overactive bladder symptoms. Int Urogynecol J. 2018;29(10):1493-1500.
15.
Siddiqui H, et al. Pathogens in Urine from a Female Patient with Overactive Bladder Syndrome Detected by Culture-independent High Throughput Sequencing: A Case Report. Open Microbiol J. 2014;8:148-53.
16.
Wolfe AJ, et al. Evidence of uncultivated bacteria in the adult female bladder. J Clin Microbiol. 2012;50(4):1376-83.
17.
Thomas-White KJ, et al. Incontinence medication response relates to the female urinary microbiota. Int Urogynecol J. 2016;27(5):723-33.