Old myths that won't die: "The bladder is sterile"

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Old myths that won't die: "The bladder is sterile"

Post by webslave »

Time to debunk all the old myths

There is a lot of recent research showing that everyone has a "urobiome", in other words a community of bacteria living inside our bladders, prostates, urethras. That's now beyond debate. And many members of the urobiome are what used to be thought of as disease-causing genera, living harmlessly alongside the "good" bacteria, which keep them in check.

Now if the urothelium is disturbed or inflamed, for whatever reason, the microbiome will be presented with a different surface to colonize, and will support more and different species. Infiltration of immune cells and inflammatory mediator production (cytokines and chemokines) leads to a breakdown of the urothelial barrier and increased tissue permeability. Host inflammation leads to increased vascularity, tissue edema, and leukocyte recruitment. With a weakened or compromised "mucosal firewall", damaged by inflammation (for instance), the urobiome will change. This has been shown in colorectal cancer:
Deficiency of T-bet (T-box transcription factor) in the innate immune system leads to exaggerated tumor necrosis factor alpha (TNF-α) production by dendritic cells, which together with the absence of Treg (regulatory T cells) creates a chronic inflammatory state that modulates the composition of the microflora and eventually leads to the development of colorectal cancer
And we know antibiotic treatment, universally imposed on anyone with LUTS, can affect the microbiome. From a 2020 review paper:
With growing knowledge of the role that the urinary microbiota plays in urogenital health, it is becoming clear that UTI and rUTI (recurrent UTI) treatment paradigms may need to consider the state of the urinary microbiome. The traditional goal of achieving UT sterility in the management of UTI and rUTI may destroy beneficial, protective microbial populations as well as pathogens. Without the beneficial microbiota, the UT may be thrown into a dysbiotic, sensitized state at risk for colonization by uropathogens.
In a 2019 report, Mulder et al. used [clean catch urine] to assess the effect of antibiotic therapy on the urinary microbiome composition of elderly people and found that antibiotic therapy was associated with an altered composition of the urinary microbiome. Interestingly, they noted that the genus Lactobacillus, which may be associated with UGT health, was significantly depleted in patients with a recent history of antibiotic use, while uropathogenic species were significantly enriched.
So, counterintuitively, antibiotics can hurt more than they help. It's self-defeating.



Great caution should be attached to attributing disease causation to an altered microbiome. Is it the cause or effect of the disease? From a 2017 review paper Meta-analysis of gut microbiome studies identifies disease-specific and shared responses :
The identification of a non-specific microbial response is an important concept that should be considered in future case–control microbiome studies. It suggests that studies should be interpreted with extra caution, as many identified microbial associations may be indicative of a shared response to health or disease rather than a disease-specific biological difference. Microbes that are non-specifically associated with multiple diseases would not be useful as disease-specific diagnostics or to address causality .... For example, there may be a group of microbes which respond to or cause systemic inflammation.
The paper also notes that "most diseases show microbiome alterations", but goes on to show that the alterations are similar in many diseases:
Strikingly, the majority of microbial responses were not specific to individual diseases; on average, 51% of a data set’s genus-level associations were genera that were associated with more than one disease. In light of this finding, it is important that researchers performing future case–control studies consider whether an identified microbial association is truly specific to their disease of interest or is instead responding to a common symptom (e.g., diarrhea) or perhaps generally associated with health or sickness.
The paper also states that "a small subset of the non-specifically disease-associated genera were relatively ubiquitous across patients". So small amounts of bad bacteria are in everyone. Finding them with Next-generation sequencing (NGS) of DNA and RNA, and then treating with endless antibiotics regimens is both harmful and counter-productive.

From An Update on the Urinary Microbiome, 2019
The stable gut microbiome can be permanently perturbed by just two courses of ciprofloxacin, resulting in a stable alternative composition. While causality is unclear, repeated antibiotic use has been linked to a variety of localized and systemic conditions such as depression, schizophrenia, and allergy/atopy. ... data suggest that antimicrobials modify the urinary microbiome, possibly selecting for more pathogenic bacteria with increased antibiotic resistance. The long-term consequences of these shifts are unclear but urge caution when considering therapeutic antimicrobial interventions. Furthermore, antibiotics for non-urologic indications may have unintended alterations to urinary microbiota
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Re: Old myths that won't die: "The bladder is sterile"

Post by webslave »

Just to underline my point about systemic inflammation affecting microbiomes, a new study shows it. Based on several studies that demonstrated that different forms of injury affect the composition of the gut microbiome within the first 72 h post injury, they anaesthetised mice, then bashed them to induce trauma and haemorrhagic shock, then euthanized them and tested the gut microbiomes:
...our results demonstrate that systemic and local inflammation as well as intestinal barrier dysfunction are associated with the diversity and community composition of the cecal microbiome.
So the host's systemic condition will influence the microbiome. If your pelvic nerves are constantly buzzing due to tension and spasm, they can cause inflammation in the urothelium (that's been shown in rodents and cats). If you inflame your urothelium, you will change your urobiome.
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Re: Old myths that won't die: "The bladder is sterile"

Post by webslave »

Yet another study that reinforces how the host's neural activity can change the microbiome.

The effect of mindfulness-based stress reduction on the urinary microbiome in interstitial cystitis
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