Functional Profiling of the Urinary Tract Microbiome Reveals Microbial Influences on Urolithiasis

Individuals with urinary stone disease (USD) exhibit dysbiosis in the urinary tract and the loss of Lactobacilli that promote urinary tract health. However, it is currently unknown how urinary tract bacteria can modify lithogenesis. The objective of the current study was to determine which specific microbial functions in the urinary tract are associated with calcium oxalate (CaOx) stone formers to better understand how the microbiome contributes to CaOx lithogenesis. Data revealed that individuals with CaOx stones harbored a distinct urinary tract microbiome overall. Specifically, CaOx stone formers had reduced levels of genes associated with oxalate metabolism, as well as transmembrane transport, proteolysis, and oxidation-reduction processes. From 17 draft genomes extracted from the data, genes enriched in the healthy group mapped overwhelming to Lactobacillus crispatus and those associated with CaOx mapped to Pseudomonas aeruginosa and Burkholderia sp. The microbial functions that differentiated the clinical cohorts are associated with known mechanisms of stone formation and thus point to specific urinary tract bacteria that play important roles in the onset of USD.