Cross-study metagenomics analysis reveals distinct microbial signatures of urinary tract infections

Abstract

BackgroundUrinary tract infections (UTIs) represent a major public health concern, increasingly complicated by rising antibiotic resistance, diminishing treatment efficacy, and increasing prevalence of recurrence. The urinary tract microbiome (urobiome) remains poorly characterized, despite its potential role in UTIs. ResultsTo provide a comprehensive overview of the urobiome, we here integrated seven publicly available shotgun metagenomics studies, linking microbial composition to clinical infection status or diagnostics. Community-level analyses revealed distinct urobiome clusters, defined by one predominant bacterial taxon. Genome-resolved metagenomics allowed recovery of high-quality metagenome-assembled genomes (MAGs), enabling phylogenetic reconstruction, prediction of pathogenic potential, and profiling of antimicrobial resistance genes across multiple taxa. We then analyzed the pangenome of the clinically significant Escherichia coli species and found that its genomic variation is driven more by phylotype than isolation source or UTI status, supporting a model of opportunistic infection. ConclusionsTaken together, our analyses represent a systematic, cross-study view of the urobiome that emphasizes the ecological complexity of the urobiome and the importance of integrating functional and phylogenetic information when studying UTIs.