Age, Menopausal Status and the Bladder Microbiome

Objectives: The bladder is not sterile but contains a healthy community of microbes termed the microbiome. Alterations in the bladder microbiome have been demonstrated in disease states such as the overactive bladder. The microbiome in other anatomical niches is known to alter with age eg the vagina. The objective of this study was to identify if the bladder microbiome in healthy women varies with age and menopausal status. Study design: Urine from 79 healthy women attending secondary care gynaecological clinics with no urinary symptoms provided clean catch mid-stream urine specimens. Urine was centrifuged and the resultant pellet was re-suspended and inoculated onto chocolate agar plates and cultured under either aerobic or anaerobic conditions. Morphologically different colonies were purity plated and 16s rRNA gene sequencing was performed. A microbe genomic basic local alignment search tool (BLAST) was used to identify the genus of the bacteria. Results: There was no significant correlation between the age of a woman and the number of different genera identified (r=-0.034, p=0.79). There were few significant differences in the frequency with which the majority of organisms were found in pre and post-menopausal women. The exceptions however were lactobacillus, which was more common in pre-menopausal women (31 vs 3 p=0.002) and Mobiluncus, which was more common in post-menopausal women (0 vs 3 p=0.02). Conclusions: There was no significant correlation between patient age and diversity of the bladder microbiome but large numbers of different organisms were identified. Significant differences were however observed for Lactobacillus which is more common in pre-menopausal women and Mobiluncus which is more common in in post-menopausal women

Management and Aetiology of Overactive Bladder

The aetiology of overactive bladder (OAB) is poorly understood. Current treatment modalities are associated with low success rates and poor long-term compliance. The aim of this thesis was to explore the new and alternative treatment, mirabegron, to assess the efficacy of traditional treatment options such as cystodistension for women with OAB and to ascertain whether underlying baseline parameters (e.g. urodynamic studies, cystoscopic findings, bladder biopsy results) have any impact on treatment outcomes. The aetiology of OAB was also studied to understand the impact of bladder wall thickness and the bladder microbiome in OAB to improve our understanding of the possible mechanisms of OAB. In this thesis, I have reviewed the current literature on OAB, cystodistension and the role of infection in OAB. The work presented in this MD investigates the effectiveness of mirabegron and cystodistension as treatment options for OAB. All studies were conducted in a 'real-life' clinical setting to recreate the challenges in daily clinical practice. Mirabegron was found to be an effective treatment option for patients with OAB. However, the benefits were not striking with 70% of patient reporting improvement of their symptoms at 6 weeks. This was converted into only a minority of patients (36%) reporting their incontinence was "much better" or "very much better". More research should be targeted at identifying patient characteristics that are associated with a better outcome. It was found to be a suitable non-invasive alternative to Botulinum Toxin A (BTXA) in 59% of patients with refractory OAB. However, over two thirds of patients discontinued mirabegron therapy within 1 year. A significant number of patient who persevered with mirabegron were on combination therapy with an antimuscarinic at 1 year. Randomised controlled trial comparing cystodistension with cystoscopy demonstrated no benefit from cystodistension in the treatment of OAB. In this group, the presence of bladder trabeculation on cystoscopy was found to be associated with a direct effect on maximum detrusor muscle contraction with a significant increase in contraction compared to patients with an absence of trabeculation (42.71 cmH2O vs 31.41cmH2O, p = 0.01). The presence of trabeculation also affected the symptoms of OAB with a significant decrease in the Filling Scores of the ICIQ-FLUTS LF questionnaire (8.45 vs 9.58, p=0.04). There was no relationship between urodynamic findings and bladder biopsy on baseline symptomology and outcome of treatment. In this cohort, a feasibility study assessing bladder wall thickness (BWT) recorded a significant increase in BWT in OAB patients with detrusor overactivity (DO) (5.6mm vs 4.2mm, p=0.006). Though ultrasound is unable to replace urodynamic studies, it may be useful tool in understanding the aetiology, disease progression and prediction of treatment outcomes in OAB. The bladder microbiome demonstrated a significant difference between the patients with OAB and healthy controls. Proteus was found to be significantly more prevalent in OAB patients (p=0.01) whilst Lactobacillus was significantly more common in healthy controls (p=0.02). The work in this MD suggests there may be variety of sub-types of OAB with different underlying mechanisms of action that may explain the large variation in outcomes with different treatment modalities. Further research will need to be performed to further explore and confirm these findings