Urinary tract infections in postmenopausal women revisited (UTIr): a prospective observational cohort study to explore the urobiomes of postmenopausal women with and without recurrent urinary tract infections.

backgroundRecurrent urinary tract infections (RUTI) are prevalent, particularly among postmenopausal women, and place a significant burden on the affected individuals and the healthcare system. While Escherichia coli is the primary cause of most UTIs in premenopausal women, this may not hold true for postmenopausal women. To facilitate development of novel diagnostics, preventive interventions, and clinical management of RUTI in postmenopausal women, it is essential to strengthen the biological evidence base.

methodsThis observational prospective cohort study will enrol 20 postmenopausal women without RUTI (controls) and approximately 30 with RUTI (cases), aiming to sample at least 50 UTI episodes. Questionnaires are completed, samples (urine, vulvoperineal and vaginal swabs, and faeces) are collected by participants or study staff at five scheduled time points over one year of follow-up, as well as during and after each UTI episode. All samples will undergo 16S rRNA amplicon sequencing, with selected urine samples also subjected to bacterial culturing, metagenomic sequencing, and metabolomics. Various urobiome comparisons will be conducted, such as between women with and without RUTI in the absence of a UTI, and over time during UTIs. Urobiomes will also be compared to vaginal, vulvoperineal, and gut microbiomes in the same women at the same time points. Finally, urine samples will be cultured to obtain bacterial isolates, which will be characterised and used for co-culture and urothelium organoid experiments. DISCUSSION: The UTIr cohort study is an exploratory, hypothesis-generating study designed to improve understanding of the ecological mechanisms driving UTI onset, response to antibiotic treatment, and UTI recurrence in postmenopausal women. The data collected from each individual woman is longitudinal and comprehensive, which is instrumental for advancing the field. The study population consists of women over the age of 50 and the study procedures are demanding. Flexibility with protocol procedures has proven to be essential to maximise retention and minimise missing data. We recommend employing a sufficiently large recruitment team and/or planning for a sufficiently long recruitment period to accommodate the demanding nature of these types of in-depth studies with vulnerable populations.

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