<strong>Interstitial Cystitis-Associated Urinary Metabolites </strong><strong>Identified by Mass-Spectrometry Based Metabolomics Analysis</strong>

Abstract

This study on interstitial cystitis (IC) aims to identify a unique urine metabolomic profile associated with IC, which can be defined as an unpleasant sensation including pain and discomfort related to the urinary bladder, without infection or other identifiable causes. Although the burden of IC on the American public is immense in both human and financial terms, there is no clear diagnostic test for IC, but rather it is a disease of exclusion. Very little is known about the clinically useful urinary biomarkers of IC, which are desperately needed. Untargeted comprehensive metabolomic profiling was performed using gas-chromatography/mass-spectrometry to compare urine specimens of IC patients or health donors. The study profiled 200 known and 290 unknown metabolites. The majority of the thirty significantly changed metabolites before false discovery rate correction were unknown compounds. Partial least square discriminant analysis clearly separated IC patients from controls. The high number of unknown compounds hinders useful biological interpretation of such predictive models. Given that urine analyses have great potential to be adapted in clinical practice, research has to be focused on the identification of unknown compounds to uncover important clues about underlying disease mechanisms.More than 3-8 million women and 1-4 million men are diagnosed with Interstitial Cystitis (IC), also known as Painful Bladder Syndrome, in the US annually 1 . IC impacts health-related qualities of life immensely, and in some instances can be more debilitating than end-stage renal disease 2,3 . In spite of an increase in the number of diagnosed cases, objective diagnostic criteria are not consistently applied in general practice 4 . Some lower urinary tract symptoms, such as overactive bladder (OAB), have symptoms in common with IC, further complicating the diagnosis. Diagnosis of the disease has been dependent on clinical parameters (e.g. pain, urgency, and frequency) due to the lack of proper conventional markers (e.g. PSA for prostate cancer diagnosis) 3,5 . Diagnostic tests include urinalysis, urine culture, cystoscopy, bladder biopsy and hydrodistention of the bladder. Nonetheless, we still lack definite criteria for the disease. Estimates of the prevalence and natural history of IC still fluctuate widely because of different diagnostic standards, populations evaluated, and challenges inherent in following patients over time 6 . Thus, the identification of sensitive and non-invasive biomarkers has the potential to greatly improve the accuracy of an IC diagnosis. However, our current understanding of mechanisms involving pelvic pain is also unclear and fragmented.Urinary metabolites represent a signature of a subject's metabolic state and may convey critical information about the pathophysiology of disease. This may be especially true for pelvic disorders because urine is the body fluid most proximal to the urinary tract. Because metabolites vary in size, chemistry and physicochemical properties, a single platform has only a ...