Overactive bladder (OAB) is common in aged male and have a major influence on quality of life (QoL). OAB patients are treated with anti-cholinergics and ß3-agonists. However, OAB symptoms persist even after treatment in some patients, which supports the fact that the mechanisms responsible for OAB remain unclear. The previous reports revealed that amino acid profile was associated with lower urinary tract symptoms (LUTS) from metabolomics analysis, which enables the detection and semi-quantitative measurement of hundreds of unique metabolites from broad range of metabolic pathways (1). In the present study, we identified metabolites from metabolomics approach and investigated association between these metabolites and urgency as a major complaint of OAB.

A total of 47 male participants without apparent neurological diseases at our outpatient clinic were enrolled in the present study; Age: 71.5+/-4.4 years old, body mass index (BMI): 23.0 +/-2.8. A 24hrs-bladder diary was carried out to assess behavior of micturition, and we used the International Prostate Symptom Score (IPSS) and QoL score to analyze LUTS and QoL. OAB was defined as a urgency score of IPSS was 2 and more (OAB-group), and patients with 0 and 1 was belong to Control-group. To investigate association with OAB in males and novel molecular insights into disease pathogenesis, we conducted a comprehensive study of plasma metabolites using liquid chromatography time-of-flight mass spectrometry (LC-TOFMS). Metabolites were compared between OAB - and Control-groups using Student t-test as a screening, and association with male OAB from metabolites in LC-TOFMS were analysed using a multivariable logistic regression analysis to reveal the odds ratio and 95% confidence interval (CI).

Of 47 participants, 26 males were in OAB-group and the other 21 males in Control-group. A 24hrs-bladder diary revealed that nocturnal urine volume, 24hrs-micturition frequency, nocturnal micturition frequency and nocturnal index were significantly higher in OAB-group. Although maximum voided volume was significantly lower in OAB-group, 24hrs-urine volume or nocturnal polyuria index was not different between groups. (Table 1) Metabolomics analysis with LC-TOFMS identified 79 metabolites from plasma of participants. In a total of 6 metabolites, there was significant difference or a trend of difference between OAB- and Control-groups. Regarding these 6 metabolites, a multivariate analysis showed that increases of FA (22:1) Erucic acid, Palmitoleic acid and cis-11 Eicosenoic acid and a decrease of cholic acid were significantly associated with incidence of OAB in males. A decrease of Glycodeoxy cholic acid  could be also associated with male OAB. (Table 2)

It hase been reported that metabolic pathways of fatty acids and bile acids are involved in metabolic syndrome (2)(3). The present study revealed that male OAB could be also associated with abnormalities in metabolic pathways of fatty acids and bile acids. Controlling metabolism of fatty acids and bile acids in plasma could be one of attractive therapeutic targets of over active bladder.

OAB in males could occur through abnormal metabolism of fatty acids and bile acids, which could be associated with metabolic syndrome. Further studies using results of metabolomics analysis have a potential to detect new biomarkers and develop potential targets for new treatments.

Mitsui T, et al., Metabolomics Approach to Male Lower Urinary Tract Symptoms: An Identification of Possible Biomarkers and Potential Targets for New Treatments. J Urol, in press, 2018
Cooke AA, et al., Fatty acids and chronic low grade inflammation associated with obesity and the metabolic syndrome. Eur J Pharmacol, 785:207-214, 2016
Taoka H, et al., Role of bile acids in the regulation of the metabolic pathways. World J Diabetes, 7:260-70, 2016