This research study seeks to provide more insight as to how the microbiome affects or is affected by conditions causing chronic pelvic pain such as Interstitial Cystitis (IC), Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS), Lower Urinary Tract Symptoms (LUTS), or Overactive bladder (OAB). Depression and many chronic pain disorders are often related and are poorly understood, and treatment is often not helpful. The goal of this study is to explain pelvic pain characteristics and causes by studying microbiomes of healthy people compared to people suffering from IC, CP/CPPS, LUTS, OAB, and Major depression.

Population

Primary care clinic patients Community sample

Brief Title

Microbiomes of Pelvic Pain

Official Title

Microbiomes of Pelvic Pain

Brief Summary

This research study seeks to provide more insight as to how the microbiome affects or is <br /> affected by conditions causing chronic pelvic pain such as Interstitial Cystitis (IC), <br /> Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS), Lower Urinary Tract Symptoms <br /> (LUTS), or Overactive bladder (OAB). Depression and many chronic pain disorders are often <br /> related and are poorly understood, and treatment is often not helpful. The goal of this study <br /> is to explain pelvic pain characteristics and causes by studying microbiomes of healthy <br /> people compared to people suffering from IC, CP/CPPS, LUTS, OAB, and Major depression.

Detailed Description

Interstitial cystitis/painful bladder syndrome (IC) or Chronic Prostatitis/Chronic Pelvic
Pain Syndrome (CP/CPPS) is characterized by chronic pelvic pain and voiding dysfunction. IC
or CP/CPPS remains an enigma within urology, with no known etiology or widely effective
therapies. However, some IC, CP/CPPS, and depressed patients suffer bowel co-morbidities, and
it is well established that the GI tract can influence bladder function, mood and sensation
via pelvic organ crosstalk. Like other body sites, the gut harbors a rich microflora. Studies
characterizing microbial diversity and relative abundance at a particular body site, the
"microbiome," reveal that microbiomes play critical roles in normal cellular and organ
function, and thus this importance is emphasized with the Human Microbiome Project (HMP), an
NIH Common Fund initiative. CPPS patients suffer chronic pelvic pain and dramatically lower
quality of life, yet diagnostic markers and effective therapies remain elusive for these
costly syndromes. IC is a debilitating condition of pelvic pain and voiding dysfunction
afflicting up to 8 million U.S. women where depression is a common co-morbidity, distinct
from over-active bladder (OAB) patients lacking pain. IC etiology remains unknown, but
urothelial lesions and lamina propria mast cells are associated with patient symptoms.
Similarly, CP/CPPS afflicts 1 in 22 men in the U.S. with pain and voiding and sexual
symptoms, again distinct from patients having only irritative voiding from lower urinary
tract symptoms (LUTS). And although leukocytes are observed in prostatic fluid of some
patients, the etiology of CP/CPPS also remains unknown. Hypothalamic-pituitary-adrenal axis
(HPA) dysfunction has been implicated in female and male patients and cats with feline IC,
and thus may be common among CPPS, but a mechanism that integrates pelvic pain, voiding
dysfunction, HPA activity, and depression is lacking.

Microbiomes are also dynamic and subject to skewing, and these changes are increasingly
associated with diseases including Crohn's disease, ulcerative colitis, obesity, and possibly
depression. Antibiotic therapies alter microbiomes, often causing temporary dysfunction and
sometimes resulting in diseases such as colitis. Since IC or CP/CPPS patients often have a
history of urinary tract infection (UTI), they typically receive multiple courses of
antibiotics. This therapeutic history of IC or CP/CPPS patients may have adverse consequences
for two reasons. First, potential skewing of the gut microbiome may alter normal sensory and
functional homeostatic mechanisms, contributing to pain and voiding dysfunction. Second, an
altered gut microbiome may foster uropathogen reservoir expansion, and our preliminary data
demonstrate urinary E. coli isolates can induce chronic pelvic pain persisting long after
microbial clearance. Together these lines of reasoning raise the provocative possibility that
microbiomes contribute to IC, CP/CPPS, and depression directly by supplying uropathogens or
indirectly through organ crosstalk dysfunction. Therefore, is an altered gastrointestinal
tract microbiome associated with IC, CP/CPPS, and/or depression? Our team marries core NIH
and NIDDK missions, digestive diseases and kidney/urologic, to address this novel question
with synergistic expertise in clinical diagnosis of IC, CP/CPPS, and depression, quantifying
GI tract microbiomes, and neural mechanisms of microbe-induced pelvic pain. Stool samples
will be analyzed by 16S rDNA sequence and in silico metagenome analyses to identify taxa,
abundance, and function. Computational tools will be used to identify taxa amenable to rapid
evaluation of stool. Stool, serum, and urine will be evaluated for small molecules specific
to CPPS, and these putative mediators will be tested in mice for effects on pelvic pain and
urinary function.

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.