Sathiananthamoorthy, Sanchutha; (2018) Characterisation of the urinary microbial community and its association with lower urinary tract symptoms. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Lower urinary tract symptoms affect 2.3 billion individuals worldwide and pose a substantial burden on the quality of life. An important step in a LUTS investigation is the exclusion of a urinary tract infection with the help of nationally recommended urine tests. These tests include the routine midstream urine culture, which is regarded as the UK’s gold standard for detecting infection. Microbial confirmation of UTI stems from criteria that were originally proposed in the 1950s, following a study that examined patients with acute pyelonephritis. Whilst the clinical diagnosis of UTI is considered to be straightforward in patients that describe hallmark symptoms, notably acute frequency and dysuria, the presentation of less well-recognised LUTS may not be as straightforward to diagnose and treat. This thesis consists of original work from three specific studies. Firstly, a retrospective observational study was conducted to compare the clinical characteristics of patients describing LUTS with a suspected UTI, on the basis of their routine MSU culture findings. This study revealed the striking clinical similarities between patients with a culture result of doubtful significance that consists of multiple organisms and patients with a positive culture that represents significant bacteriuria. Secondly, an evaluation of the UK’s MSU culture was performed by comparing the microbial yield achieved with three different culture techniques. Additionally, the urinary bacterial community, represented by the cultured spun urinary cell sediment was characterised in three different cohorts. These were (i) first-visit symptomatic patients suspected to have a UTI, (ii) chronic patients with recurrent or unresolved LUTS from a previous symptomatic episode and (iii) asymptomatic individuals. Species-level microbial identification was achieved with matrix-assisted laser desorption ionisation time-of-flight mass spectrometry. The criteria used to determine significant bacteriuria and the technique employed to perform the MSU culture were identified as factors with the potential to limit the microbiological detection of UTI. Finally, following the disproved assumption of the healthy urinary tract as a sterile environment, molecular characterisation of LUTS patient and asymptomatic control urinary tract bacterial communities was achieved using 16S rRNA gene sequencing. The core bacterial taxa shared by both patient and healthy communities were determined, with Enterobacteriaceae identified as the most abundant bacterial group in patients and Streptococcus noted as the most abundant taxa in controls. Analysing unspun urine combined with concentrated urinary cell sediment significantly discriminated between the species richness of both communities. The presented original work establishes the potential significance of mixed growth urine cultures, prompting the question of their dismissal without further investigation. In addition to identifying the limitations of the UK’s MSU culture, the complex bacterial communities of asymptomatic and LUTS patients have been characterised mostly at the genus level and established as a foundation for subsequent functional characterisation to help elucidate the mechanisms involved in LUTS and UTI development.

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