Urinary biochemical ecology reveals microbiome-metabolite interactions and metabolic markers of recurrent urinary tract infection.

Recurrent urinary tract infections (rUTIs) are a major clinical challenge in postmenopausal women and their increasing prevalence underscores the need to define interactions between the host and the urinary microbiome that may underlie rUTI susceptibility. A body of work has identified the taxonomic profile of the female urinary microbiome associate with aging, menopause, and urinay disease. However, how this microbial community engages with the host niche, including the local biochemical environment of the urogenital tract, in health and disease is yet to be fully defined. This study directly assesses differences in the biochemical environment of the urine, or biochemical ecology, associated with recurrent urinary tract infection (UTI) and defines a microbe-metabolite association network of the female urinary microbiome. By integrating metagenomic and metabolomic data collected from a controlled cohort of women with rUTI, we find that distinct metabolites, such as methionine sulfoxide (Met-SO) and trimethylamine oxide (TMAO), are associated with differences in urinary microbiome diversity. We observe associations between microbial and biochemical beta diversity and unique metabolic networks of uropathogenic and uroprotective species, highlighting potential metabolite-driven ecological shifts that may influence UTI susceptibility. We identify a urinary lipid signature of active rUTI that can accurately distinguish (AUC = 0.987) cases controls. Finally, using time-to-relapse data we identify deoxycholic acid (DCA) as a new prognostic indicator for rUTI recurrence. Together these findings suggest that systemic metabolic processes may influence susceptibility, opening new avenues for therapeutic intervention and the development of more accurate diagnostic and prognostic to improve patient outcomes.