Urinary tract infections: addressing the gender gap and advancing microbial insights

Historically, research and treatment approaches have relied on outdated diagnostic criteria, often overlooking recent advances in microbiome research and non-antibiotic therapeutic strategies. This article highlights the gender disparity in UTIs, the role of the urobiome, and emerging diagnostic and treatment innovations.

The gender gap in UTIs

Women are significantly more prone to UTIs than men, with approximately 50% experiencing at least one infection in their lifetime, and up to 30% suffering recurrent infections within six months. While anatomical differences have been suggested as a key factor, growing evidence indicates that hormonal changes, immune response differences, and the vaginal microbiota play crucial roles. Furthermore, the high recurrence rate of UTIs in women has substantial social and economic implications, including lost workdays, diminished quality of life, and increased antibiotic use, exacerbating antimicrobial resistance (AMR) concerns.

Despite these burdens, UTIs are often overlooked as a gendered health issue, leading to inadequate research funding and limited innovation in treatment strategies. Recent calls for a more inclusive approach to UTI research emphasize the need for personalized treatment protocols that consider biological and social determinants of health.

Microbiome and UTI susceptibility

The human urinary tract was long thought to be sterile, but recent findings have identified a diverse microbial community—now referred to as the urobiome—which plays a crucial role in urinary health. Dysbiosis, or microbial imbalance, has been linked to increased susceptibility to UTIs, with reductions in beneficial lactobacilli and overgrowth of pathogenic bacteria such as Escherichia coli and Klebsiella pneumoniae.

The gut-bladder axis also contributes to UTI risk. Emerging evidence suggests that disruptions in gut microbiota composition can influence bacterial colonization of the urinary tract, emphasizing the need to consider whole-body microbiome interactions in UTI prevention and treatment. Understanding these microbial dynamics is critical for developing targeted therapies aimed at restoring microbial balance rather than relying solely on antibiotic interventions.

Challenges in diagnosis

Conventional urine culture remains the gold standard for UTI diagnosis; however, it has significant limitations. Studies indicate that standard culture techniques fail to detect many bacterial species present in UTIs, particularly those forming biofilms or existing in a viable but nonculturable (VBNC) state. Approximately 24% of symptomatic patients with pyuria (white blood cells in urine) do not show bacterial growth in conventional cultures, leading to misdiagnosis and inappropriate treatment.

Additionally, the Kass criterion (≥10⁵ CFU/mL bacterial threshold for UTI diagnosis) has remained largely unchanged since the 1950s, despite growing evidence that lower bacterial counts can also contribute to symptomatic infections. The inclusion of next-generation sequencing (NGS) and expanded quantitative urine culture (EQUC) methods in clinical diagnostics could improve detection and inform more effective treatment strategies.

Advances in treatment

The reliance on antibiotics for UTI treatment has led to a surge in multidrug-resistant (MDR) uropathogens, making alternative therapies increasingly necessary. Several promising approaches are under investigation:

• Probiotics and Prebiotics: Lactobacilli-based probiotics have shown potential in preventing UTI recurrence by restoring urobiome balance and inhibiting pathogen colonization.
• Vaccines: Experimental vaccines targeting Uropathogenic Escherichia coli (UPEC) and other uropathogens have demonstrated protective immunity in preclinical and early clinical trials.
• Bacteriophage Therapy: The use of bacteriophages—viruses that selectively infect and destroy bacteria—is a novel approach gaining traction as a potential solution for antibiotic-resistant infections.
• Cranberry Extract and D-Mannose: These supplements have been suggested to reduce bacterial adherence to the bladder epithelium, though clinical efficacy remains debated.
• Immunomodulation Strategies: Understanding the immune response in UTIs could lead to targeted therapies that enhance host defenses while minimizing inflammation-related damage

Conclusion

The traditional approach to UTIs – characterized by antibiotic overuse, outdated diagnostic criteria, and an underappreciation of the microbiome’s role – must evolve. A gender-inclusive perspective, combined with advances in microbiome research and novel therapeutic interventions, is essential for improving UTI prevention, diagnosis, and treatment. Future research should prioritize personalized, microbiome-conscious strategies to address this persistent and often-overlooked health issue.

Author: Paola Scavone

Laboratorio de Biofilms Microbianos

Departamento de Microbiología

Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay