Urinary Microbiome and Its Correlation with Functional Disorders of the Genitourinary Tract

Javan A1, van Koeveringe G2, Voegeli T3, Hajebrahimi S4, Rahnama'i M3

Research Type

Pure and Applied Science / Translational

Abstract Category

Female Lower Urinary Tract Symptoms (LUTS) / Voiding Dysfunction

Abstract 602
E-Poster 3
Scientific Open Discussion Session 31
Friday 6th September 2019
13:35 - 13:40 (ePoster Station 5)
Exhibition Hall
Detrusor Overactivity Female Voiding Dysfunction Painful Bladder Syndrome/Interstitial Cystitis (IC) Infection, other
1.6. Society of Urological Research and Education (SURE), Heerlen, The Netherlands, 2.Maastricht University, 3.Uniklinik RWTH Aachen, Germany, 4.Research Center for Evidence Based Medicine (RCEBM), Tabriz University of Medical Sciences, Tabriz, Iran

Aida Javan




Hypothesis / aims of study
The lower urinary tract comprises the bladder and the urethra and is supported by muscles and ligaments. The urethra contains both smooth and striated muscles. The inner lining of the bladder is called the urothelium, which also has a barrier function. 
According to the International Continence Society (ICS), Lower Urinary Tract Symptoms (LUTS) can be divided into storage symptoms, voiding symptoms and post-micturition symptoms. LUTS in male patients is usually attributed to benign prostatic enlargement and bladder outlet obstruction and in female patients predominantly to the over active bladder syndrome (OAB). [1-3] The definition of OAB includes symptoms of urinary urgency, with or without urinary incontinence, usually accompanied by increased urinary frequency and nocturia. [1-3]  
Urinary urgency is defined as a sudden and compelling desire to void, which in case of patients with OAB, cannot be postponed. In contrast, detrusor underactivity (DU) is associated with a reduced ability to void and is accompanied with voiding and post micturition symptoms and can predispose to UTI and acute urinary retention. The aetiology of detrusor underactivity is influenced by multiple factors, including ageing, bladder outlet obstruction, neurological disease, and autonomic denervation.
Until recently, urine of healthy individuals has been considered to be sterile, however new bacteria detection techniques have proven this assumption to be wrong. Urine of asymptomatic, healthy individuals contains a certain microbiome. 
‘‘Microbiota’’ refers to the assemblage of living microorganisms present in a defined environment. This is a crucial part of the ‘‘microbiome’’, which can be used to refer to the entire habitat, including the microorganisms (bacteria, archaea, lower and higher eukaryotes, and viruses), their genomes, and the surrounding environmental conditions. 
The Human Microbiome Project (HMP) has been investigating these microbiome communities in body. However, the focus mainly has been on organs like the skin, the mouth, the genital tract, the eye, the gut and the blood. 
In this study, we give an overview on all the available published literature on the relationship between the urinary microbiota and functional disorders of the genitourinary tract, including bladder pain syndrome, prostatitis, stone disease and bladder cancer. [Table 1].
Study design, materials and methods
We present a systematic review of the available literature on microbiome and functional disorders of the genitourinary tract. The studies were searched through PubMed, Medline and Cochrane databases. The MeSH search was conducted through the association of microbiome and microbiota with genitourinary tract disorder, urinary tract symptom, urinary tract infections, overactive bladder, urinary incontinence, interstitial cystitis, bladder pain syndrome, chronic prostatitis, pelvic pain, scrotalgia, kidney stones, bladder Cancer. The initial search identified 743 studies.  All included studies were written in English and were published between January 2007 and October 2018. Of the 753 identified citations, 504 were non – duplicate and thus admissible. Two hundred and twenty eight were excluded after screening the title and abstract. Of the remaining 276, one hundred and fifty-two were eliminated., having reviewed the entire length of the articles. Ultimately; 124 studies were selected for inclusion in the review and Meta-Analyses (PRISMA) methodology. Of these 124, 40 were directly regarding microbiome and microbiota.
In classical view, urine of healthy individuals was thought to be sterile and the sterility of healthy urine was thought to be maintained by host factors such as the physical barriers between the source of pathogenic bacteria and the urinary tract, ongoing flow of urine through the urinary tract, and complete bladder emptying when voiding, as well as antibodies, proteins, and factors that kill or restrict the ability of the microbes to grow infect. 
Hence, the sterility of urine is now under debate. The diversity discovered between the urinary microbiota of fit, well-conditioned, ambulatory subjects possessing lower urinary tract dysfunction could encompass an etiological constituent in numerous bladder disorders. The prospect of diagnosis and a curative application is expeditious. 

“Microbiota” is a collection or community of microbes.  “Microbiome” refers to the full collection of genes of all these microbes.  Opposite 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 tract, the skin, upper respiratory and the genital tracts. There are different elements contributing to shape characteristics of the microbiome communities in the body. To name a few: age, gender, hormonal status, body mass index, diet, environment, host genetics, and early microbial exposure and some clinical conditions definitely have influence. 
Furthermore, for these bacterial populations, being beneficial and pathogenic is a relative concept depending on the individual’s microbiome characteristics. 
A standard urine culture does not identify slow growing, anaerobic and fastidious bacteria. However, rather positively; culture independent methods, in particular 16S rRNA gene sequencing, have established that standard urine culture protocols are incapable of distinguishing the preponderance of bacteria living in urine samples. They have been used as a primary technique in the Human Microbiome Project, to elucidate the composition of the microbial communities in different microbial niches of the human body. In addition, NGS has been used in many studies to describe the microbiota in urine collected from the bladder of subjects with and without manifestation of LUT symptoms.
Interpretation of results
Evidence proves the bladder to contain microbiomes which under standard conditions are not perceivable. Whether they stand to benefit us or have pathogenic roots is dependent upon the singular microbiome characteristic. In regard to the uncovering of the relationship between microbiome and the lower urinary tract symptom, there has been a gargantuan amount of research in recent years. 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. In all the studies concentrating on the relation among microbiome and OAB, the demonstration was made that Lactobacillus in patients suffering from OAB had increased in comparison to the subjects without the condition. However; in only one study a decrease in Lactobacillus was observed with an increase of Gardnerella spp..In another study in patients suffering from OAB, an increase in Streptococcus compared to healthy subjects was observed. In the case of BPS/IC patients, it was evident that these patients had an increase in Lactobacilli. So far, there is still no evidence provided of a relation between the urinary tract microbiome and Detrusor Overactivity. As regards to the CP/CPPS , in one study Burkholderia cenocepacia was detected. In a seperate study, a increase in the Enterococcus levels was witnessed where as the Escherichia coli were decreased. In a thord study, it was seen that the Clostridiae and Bacteroidetes were increased. In the studies focusing on BC, Streptococcus had na increase in one and the other had na increase in Staphylococcus aureus.
Concluding message
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.
Figure 1
  1. Abrams, P., et al., The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology, 2003. 61(1): p. 37-49.
  2. Abrams, P., et al., Reviewing the ICS 2002 terminology report: the ongoing debate. Neurourol Urodyn, 2009. 28(4): p. 287.
  3. Haylen, B.T., et al., An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Neurourol Urodyn, 2010. 29(1): p. 4-20.
Funding This study was funded byaresearch grant from Forum Urodynamicum Germany Clinical Trial No Subjects None
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