Exloring the impact of aging on Lower Urinary Tract Symptoms (LUTS) : a longitudinal observational cohort study focusing on the genome-exposome interplay

Hypothesis / aims of study: Aging poses significant challenges in the 21st century, with the global elderly population (>65 years) expected to nearly double by 2050. The rise in those aged >85 is linked to increased chronic diseases prevalence. (1) Understanding age-related disease epidemiology and the complex interplay between genetics and environmental factors (genome-exposome interactions, GxE) is essential to address risk factors and promote healthy aging. (2) Lower Urinary Tract Symptoms (LUTS) have evolved from individual complaints to a clinical diagnosis, now considered a functional unit with a lifelong nature. (3) Current literature suggests bidirectional influences of insomnia on nocturia and associations between the microbiome and LUTS, though causality remains unproven. This longitudinal study explores age-stratified LUTS prevalence, associated risk factors (e.g., sleep disturbances, urinary or gut microbiota) and LUTS incidence over time. Study design, materials and methods: This longitudinal observational cohort study examines 20,000 Belgian urban residents over a time-period of 20 years in collaboration with the local university, the city council, the university hospital and an interuniversity microelectronics centre. This cohort includes all consenting residents aged > 45 from five districts, with no exclusion criteria applied. Figure 1 shows the standardized study flowchart. After signing informed consent, participants will complete digital questionnaires on urinary symptoms (ICIQ-LUTS, ICIQ-Nocturia), sleep quality (PSQI), quality of life (EQ-5D-5L) and sociodemographic parameters. An environmental scan of living conditions will be performed. Afterwards, participants will be invited for physical examination and bio-sampling will take place (samples of urine, blood, stool, saliva, skin, hair). Follow-up occurs every 4 years. Statistical methods include multivariable regression models and longitudinal analysis of LUTS prevalence and incidence. Results: At this stage, data collection is ongoing and results have not yet been fully analyzed. However, trends and correlations will be identified between LUTS prevalence and various factors, including sleep disturbances, microbiota imbalances and environmental exposures. This longitudinal observational cohort study allows for the tracking of symptom progression and incidence over time, which will provide valuable insights into the contributing factors to LUTS in an aging population. Interpretation of results: This cohort study will clarify the role of genetic and environmental factors in the onset and progression of LUTS. The hypothesis that sleep disturbances, microbiota changes and environmental factors contribute to LUTS will be tested through longitudinal analysis. These results will deepen understanding of the complex factors influencing urinary health and advocate for comprehensive approaches to promote well-being across the lifespan. Concluding message: Belgium has a shortage of large-scale population-based studies, making the operational infrastructure of this study a crucial response to this gap. Promotion of personalized, predictive, preventive healthcare to enhance quality of life and healthy aging, is mandatory. Raising awareness of lifelong LUTS is essential and preventive urological healthcare must address unmet needs. Identifying predispositions from biological, environmental and hereditary factors is vital for future interventions. De-stigmatizing LUTS and developing strategies for persistent symptoms will help improve treatment options and patient outcomes.