Microbiomes of Interstitial Cystitis

Interstitial cystitis/painful bladder syndrome (IC/PBS) is characterized by chronic pelvic pain and voiding dysfunction. IC remains an enigma within urology, with no known etiology or widely effective therapies. However, some IC patients suffer bowel co-morbidities, and it is well established that the GI tract can influence bladder function 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. Microbiomes are also dynamic and subject to skewing, and these changes are increasingly associated with diseases including Crohn's disease, ulcerative colitis, and obesity. Antibiotic therapies alter microbiomes, often causing temporary dysfunction and sometimes resulting in diseases such as colitis. Since IC patients often have a history of urinary tract infection (UTI), they typically receive multiple courses of antibiotics. This therapeutic history of IC 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 directly by supplying uropathogens or indirectly through organ crosstalk dysfunction. Therefore, is an altered gastrointestinal and/or reproductive tract microbiome associated with IC? Our team marries core NIH and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) missions, digestive diseases and kidney/urologic, to address this novel question with synergistic expertise in clinical diagnosis of IC, quantifying GI and reproductive tract microbiomes, and mechanisms of microbe-induced pelvic pain.