Sex shapes the human genitourinary microbiome, including many species recognized as uropathogens: urine profiles from a population-level shotgun metagenomics study

Background The urinary tract was long considered sterile. Discovery of the urinary microbiome has attracted interest in its role in urinary health and disease. Population-level urinary microbiome composition remains poorly defined and previous studies relied on selected populations and low-resolution sequencing. We characterized urine microbiota in a large Swedish population cohort using shotgun metagenomics. Methods We performed shotgun metagenomic sequencing urine samples from 2,062 participants of the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS; 55% women, 50-65 years). Results Among 3,668 identified species, 90% were classified to species level. Males showed higher Shannon and inverse Simpson diversity, while richness did not differ by sex. Age showed only modest associations with alpha diversity. Beta diversity differed by sex, with greater dispersion among females, whereas age had minimal effects. Microbial communities differed substantially between sexes, with lactobacilli and bifidobacteria enriched in females, while Cutibacterium acnes, Enterococcus and Propionimicrobium lymphophilum were in males. Uropathogens including Enterococcus faecalis or Escherichia coli were common despite participants reporting no urinary symptoms. Conclusions In this large population-based study, we provide detailed characterization of urine microbiota, revealing marked sex differences and frequent uropathogen carriage. These findings broaden the concept of a normal urogenital microbiome and emphasize the importance of sex in studies of urinary or urogenital microbiome function.