Microbiome, Metabolome, and Microbiome-Based Therapeutics in Urological and Infectious Diseases: Decoding the Gut-Urinary Axis

The human microbiome has emerged as a central determinant of host health, shaping immune responses, metabolic homeostasis, and susceptibility to infection across all stages of life. While extensive research has focused on the gut microbiome in the context of gastrointestinal and systemic diseases, the gut-urinary (gut-bladder) axis, the bidirectional functional relationship between gut microbial communities and the urinary tract, remains a critically underexplored frontier in infection microbiology. Urinary tract infections (UTIs) represent one of the most prevalent infectious diseases worldwide, affecting individuals across all age groups and accounting for a significant proportion of antibiotic prescriptions globally. Despite decades of research, recurrent UTIs and treatment failure continue to pose major clinical challenges. Emerging evidence points toward the gut microbiome as a primary reservoir for uropathogens such as Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., and Enterococcus spp., which may translocate to the urinary tract under conditions of dysbiosis and impaired gut barrier integrity. Simultaneously, the urinary microbiome (urobiome), long dismissed as sterile, is now recognized as a dynamic microbial ecosystem influencing infection risk, pathogen colonization resistance, and treatment outcomes. Together, gut and urinary dysbiosis form an interlinked pathogenic network that conventional culture-based diagnostics and antibiotic-centric therapies fail to adequately address.

Microbially derived metabolites, including short-chain fatty acids (SCFAs), secondary bile acids, tryptophan catabolites, polyamines, and glutamate pathway intermediates, play essential roles in modulating epithelial integrity, innate immune activation, and the urinary microenvironment. Disruption of these metabolite networks under dysbiotic conditions promotes chronic inflammation and pathogen persistence. The intersection between microbiome composition, metabolite signaling, and host immune responses across the gut-urinary axis represents a promising yet insufficiently characterized field of study. Furthermore, urological conditions characterized by structural or functional perturbations, such as congenital anomalies of the kidney and urinary tract (CAKUT), vesicoureteral reflux (VUR), urolithiasis, neurogenic bladder, and catheter-associated urinary tract infection (CAUTI), add further complexity. These disorders interact with dysbiotic microbial communities to drive recurrent infection, antibiotic overuse, and long-term organ impairment. While antibiotic prophylaxis remains a common preventive practice, its effects on the resistome, microbiome diversity, and immune adaptation remain poorly understood.

This Research Topic aims to advance understanding of the microbial, metabolic, and host immune dynamics that underpin urological and infectious diseases. It seeks to bring together mechanistic, translational, and clinical research exploring the gut-urinary axis, urinary microbiome, and metabolome as sources of diagnostic insight and therapeutic innovation. By integrating microbiome science, metabolomics, and precision medicine approaches, this Research Topic will illuminate new pathways toward microbiome-targeted interventions, improved infection management, and reduced antibiotic dependency across patient populations.

To gather further insights into microbiome–metabolome–host interactions in urological and infectious diseases, we welcome articles addressing, but not limited to, the following themes:

o Gut-urinary axis mechanisms: Microbial translocation, pathobiont enrichment, gut barrier dysfunction, and metabolite-mediated cross-talk between the gut and urinary tract in UTI susceptibility and recurrence

o Urobiome characterization and functional profiling: Compositional and functional diversity of the urinary microbiome in health and disease; age-, sex-, and condition-specific urobiome signatures using 16S rRNA, metagenomics, or culturomics approaches

o Dysbiosis in structural and functional urological conditions: Gut and urinary microbiome alterations in CAKUT, VUR, neurogenic bladder, urolithiasis, and catheter-associated infections; links between host microanatomy and infection risk

o Microbial metabolites as immune and epithelial modulators: Roles of SCFAs, bile acids, tryptophan metabolites, and other microbial products in urinary tract epithelial integrity, immunity, and colonization resistance

o Impact of antibiotics and prophylaxis: Effects of therapeutic and long-term antibiotic use on gut and urinary microbiome diversity, resistome dynamics, and disease outcomes

o Microbiome-based therapeutics: Evaluation of probiotics, prebiotics, synbiotics, postbiotics, phage therapy, and fecal microbiota transplantation (FMT) as adjuncts to current UTI management strategies

o Multi-omics integration and computational analysis: Applications of metagenomics, metatranscriptomics, metabolomics, and proteomics in gut-urinary studies; AI and machine learning for biomarker and risk prediction

o Systemic infection and cross-organ microbial axes: Gut microbiome as a reservoir for systemic infection; gut–kidney, gut–bladder, gut–lung, and gut–liver crosstalk in infectious and inflammatory disease

o Longitudinal and evolutionary insights: Temporal changes in microbiome and metabolome profiles during infection onset, recurrence, and recovery; microbiome trajectories as predictors of clinical response

o Clinical translation and precision medicine: Development of microbiome and metabolome biomarkers for diagnosis and risk stratification; design of clinical trials for microbiome-targeted therapies; standardization of omics methodologies

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review

Keywords: UT-urinary axis, Urinary microbiome, Urinary tract infections, Microbial metabolites, Microbiome-based therapeutics

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.