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Once thought to be sterile, the bladder contains microbes that could influence health

Nowadays, it is quite interesting to see how omics sciences are advancing our knowledge; the molecular techniques of genomics, metagenomics, and proteomics can precisely determine the composition and diversity of the microbial communities that are present in various anatomical sites and can identify metabolites that are produced by microorganisms located there.

Thus, studies in this regard are progressively and rapidly increasing, and consequently, body sites such as the bladder, which were erroneously considered sterile until a few years ago, are now seen differently. Moreover, before metagenomics was introduced, urine samples were studied using standard techniques based on culture in media that allowed the growth of a limited number of bacteria, such as Escherichia coli, while losing the possibility of highlighting the presence of other species.

Today, we know that kidneys, the urinary tract, the bladder, the endometrium, and even ovaries host their own peculiar microbiota [1]. In fact, it is currently accepted not only that healthy subjects stably host a microbiota in the urinary tract, but also that this microbiota differs from subjects with urogenital disorders [2-7]. However, as with other human body samples with low biomass microbiome, such as breast milk, the variability of methods for urine collection, processing, and analysis may lead to conflicting results between studies about the urinary microbiome.

 

The gut-bladder axis emerges as another dimension of microbiome health

Urogenital infections affect more than one in two women, and over 10% of these patients become carriers of antibiotic-resistant bacterial strains [8,9]. The gut microbiota is a reservoir for uropathogenic bacteria such as E. coli, while its exact role in urinary tract infections (UTIs) is unknown. Thus, a shift in how we conceptualize the relationship between urogenital and gut microbiota is mandatory.

The biological and microbiological systems of various organs are communicating continuously through connection networks that play a fundamental role in maintaining homeostasis [10]. We are used to consider only the communication between two organs when we speak about “axis” (e.g. gut-urogenital axis, gut-brain axis, etc.).

However, this is an oversimplification of a complex relationship between the host and its microbiota, which is not limited to the dialogue between two distinct biological places or axes. It constantly and simultaneously involves the entire host-microbiota ecosystem; direct and indirect signals ubiquitously exchanged via chemical transmitters, neural pathways, and the immune system [11].

By keeping in mind the complex and mutual influence between ecosystems, it is fundamental to understand the importance and impact that gut dysbiosis may have on vaginal and urinary ecosystems and vice versa. This is crucial to clarify the pathophysiology of urogenital diseases and, therefore, target both research and patient care.

 

From bench to bedside: emerging interventions targeting the gut-bladder axis

It is valuable and necessary to consider that the gastrointestinal system and its microbiota are closely communicating. In addition, this may help us to understand the genesis of clinical signs and the onset and development of symptoms. It has also been hypothesized that an imbalance in the urogenital-gut-brain axis, with a consequent dysregulation of the related communication pathways, could determine a state of visceral hypersensitivity, amplified sensitivity, and hyperalgesia of the urogenital tract. This viewpoint would also explain the complex symptoms that arise in patients with relapsing and interstitial cystitis, who often present an altered emotional/cognitive state, anxiety, mood deflection, and hypervigilance [12].

UTIs afflict an estimated 1 billion women each year. While antimicrobial agents are the most frequent therapeutic option, they are usually accompanied by side effects and secondary infections, which has prompted scientists to explore exogenous (including oral) administration of lactobacilli as an alternative management regimen to antimicrobial treatment and prophylaxis [13]. From this perspective, the administration of specific strains of probiotics could play an increasingly important role in urogenital health. [14, 15].

Considering probiotics as bioactives is also important because this would allow physicians to reduce the prescription of antibiotics and consequently reduce antibiotic resistance. Other ways to balance the vaginal microbiome are currently being explored. They include adding probiotics to standard of care in bacterial vaginosis [16] and performing vaginal microbiome transplants [17].

In conclusion, emerging evidence suggests there is a urinary microbiome that might be involved in the onset of UTIs. While it remains to be seen whether there is a stable urinary tract microbiome and its physiological relevance, interventions-such as probiotics or defined fecal microbiota transplants-added to the current standard of care could help people with UTIs who do not respond to antibiotics.

 

 

References:

  1. Zucko J, Melvan, Oros, Starcevic, et al. Current Viewpoint on Female urogenital Microbiome – The cause or the consequence? Microganisms 10.3390/microrganisms 11051207 -2023
  2. NIH HMP Working Group; Peterson, J.; Garges, S.; Giovanni, M.; McInnes, P.; Wang, L.; Schloss, J.A.; Bonazzi, V.; McEwen, J.E.; Wetterstrand, K.A.; et al. The NIH Human Microbiome Project. Genome Res. 2009, 19, 2317–2323. [CrossRef] [PubMed]
  3. Oros, D.; Ceprnja, M.; Zucko, J.; Cindric, M.; Hozic, A.; Skrlin, J.; Barisic, K.; Melvan, E.; Uroic, K.; Kos, B.; et al. Identification of Pathogens from Native Urine Samples by MALDI-TOF/TOF Tandem Mass Spectrometry. Clin. Proteom. 2020, 17, 25. [CrossRef] [PubMed]
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  7. Perez-Carrasco, V.; Soriano-Lerma, A.; Soriano, M.; Gutiérrez-Fernández, J.; Garcia-Salcedo, J.A. Urinary Microbiome: Yin and Yang of the Urinary Tract. Front. Cell. Infect. Microbiol. 2021, 11, 617002. [CrossRef]
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  17. National Library of Medicine. Vaginal Microbiota Transplant (MOTIF). Available on: https://clinicaltrials.gov/study/NCT04046900