||Host responses to UTI and emerging therapeutics
||Effect of the urinary micro biome on sacral neuromodulation in women with UI
||The bladder urothelium in urinary microbiome-brain crosstalk
||The human micro biome and probiotics on bladder health
Urinary tract infections due to colonization by uropathogenic E. coli are characterized by inflammatory and symptomatic responses. In contrast, asymptomatic bacteriuria associated with E. coli are asymptomatic by definition, pointing to distinct bacterial pain phenotypes in the bladder. We are exploring the mechanisms underlying bacterial pain phenotypes in the bladder using murine models that recapitulate key clinical findings. We find that E. coli exhibit distinct pain phenotypes independent of inflammation and that specific strains possess analgesic properties amenable for development as therapies for urologic disease.
The urinary microbiota differs in women with UUI versus women who do not experience UUI. Likewise, we recently discovered the urinary microbiota of women with Interstitial cystitis/Painful bladder syndrome (IC/PBS) differs from age-matched controls without bladder pain. These studies suggest that the urinary microbiome plays a role in the development and continuation of urinary symptoms. It is possible that the urinary microbiome is responsible for producing an inflammatory state that exacerbates symptoms and influences treatment outcome, including response to SNM. We hypothesize that the urinary microbiome of treatment non-responders will be dominated by pro-inflammatory .In contrast, the microbiome of responders will be dominated by organisms that reduce inflammation (e.g. Lactobacillus gasseri) and are actively investigating this.
In order for the urinary microbiota to communicate with the brain, the bladder urothelium would be the most likely initiator of the host response to bacteria. The urothelium has been described to have “sensor-transducer” function with ability to react to stimuli such as stretch, acid, lipopolysaccharides (LPS), and bacteria. We present data on how urothelial cells react to LPS and bacteria to demonstrate novel roles for the large conductance calcium activated voltage gated potassium channel (BK or maxiK channel) and estrogen receptor β (ERβ). Therefore, urothelial BK and ERβ could play a role in the urinary microbiota – brain interactions.
At epithelial sites where microbiome is present, microbial members play an integral role in the homeostasis of the site. With the relatively recent finding that the bladder has its own microbiome, we are moving towards determining what is its role in health and disease? The microbiome may play a role in conditions, such as continence and it might be possible in the future to positively modulate host responses by using probiotics or microbial components.