Overactive bladder syndrome (OAB) is strongly associated with advanced age and metabolic syndrome. However, the exact events linking these pathologies remain to be clarified. Urinary metabolome is a useful tool to diagnose metabolic alterations that can impact bladder physiology. We aim to identify specific metabolic markers of overactive bladder syndrome (OAB) using urine metabolomics of an aging female population and to correlate potential marker levels with symptom severity.

After obtaining the required ethical approval, forty female patients (20 OAB patients and 20 healthy subjects) between the age of 50 and 80 years-old underwent clinical evaluation and lower urinary tract symptoms assessment with validated questionnaires (OABSS, ICIQ-SF, IIQ-7). Patients with cancer, diabetes, pelvic organ prolapse, kidney and liver failure were excluded. Participants completed a 3-day voiding diary and blood sampling. Early morning mid-stream urine samples were collected for urine culture and metabolomics analysis. The urinary metabolome was analyzed by gas chromatography-mass spectrometry (GC-MS) and normalized to creatinine. ANCOVA was performed to control for the effect of age.

Patients in the OAB group had a significant higher mean age, reflecting a higher prevalence with advancing age (56.3 years ± 5.2 control vs 68.9 ± 11.4 OAB, p<0.001). Serum analysis showed higher insulin resistance index (HOMA-IR) and serum urea in the OAB patients, when controlled for age (Table 1). Urine metabolomics analysis showed higher levels of urinary mitochondrial dysfunction (itaconic, malic and fumaric acids), oxidative stress (L-pyroglutamic and -hydroxyglutaric acids), and ketosis (a-hydroxybutyric and a-hydroxyisobutyric acids) intermediates in OAB patients, with values correlating significantly with OAB symptoms assessed by questionnaires (Table 2). Multiple linear regression model showed that age, blood glucose and urine metabolites (malic, fumaric and -hydroxyisobutyric) are significant predictor factors of OAB severity assessed by questionnaire scores.

The increased incidence of OAB with aging is also associated with increased insulin resistance and metabolic stress, independenty of age. The urine metabolome identified metabolic stress intermediates that correlated with the severity of OAB symptoms. This association could indicate that the increased level of these metabolites results from OAB, or rather that their production impacts bladder physiology and leads to OAB.

This study proposes new urinary metabolites to serve as biomarkers of OAB and explains its link to metabolic syndrome. These metabolites can also help in predicting OAB severity.