Urinary tract infections (UTIs) are among the most common bacterial infections and represent a significant clinical challenge owing to their high recurrence rates, repeated antibiotic exposure, and increasing antimicrobial resistance. Traditionally, the urinary tract has been considered a sterile environment, with infection developing as a result of the ascending entry and proliferation of uropathogens, most commonly uropathogenic Escherichia coli (UPEC). Advances in molecular methods, 16S rRNA gene sequencing, and expanded quantitative urine culture (EQUC) have challenged this concept by demonstrating the presence of resident microbial communities in the bladder, collectively referred to as the urinary microbiome or urobiome. Current evidence suggests that the pathogenesis of UTIs, particularly recurrent infections, involves complex interactions among the urinary, gut, and vaginal microbiomes, uropathogens, and local host defense mechanisms. The loss of potentially protective Lactobacillus spp., increased abundance of Gardnerella, Prevotella, and Enterobacterales, gut and vaginal reservoirs of UPEC, intracellular bacterial persistence, biofilms, and antibiotic-induced dysbiosis may contribute to the development and recurrence of UTIs. This review discusses current concepts of the urinary microbiome, the gut–vaginal–urinary axis, and potential microbiome-modulating approaches to the prevention of recurrent UTIs.
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