Microbial Biocatalysis within Us: The Underexplored Xenobiotic Biotransformation Potential of the Urinary Tract Microbiota

Abstract

Enzymatic biotransformation of xenobiotics by the human microbiota mediates diet-drug-microbe-host interactions and affects human health. Most research on xenobiotics has focused on the gut microbiota while neglecting other body sites, yet over two-thirds of pharmaceuticals are primarily excreted in urine. While microbial biomass and residence time in the gut is higher, xenobiotic biotransformations in the bladder have the potential to affect xenobiotic-microbe interactions including antibiotic resistance and urinary tract infections. However, we have limited knowledge of biotransformations catalyzed by the urinary microbiota. In this perspective, we investigated differences in physicochemical conditions and microbial community compositions between gastrointestinal and urinary tracts. We used a comparative enzyme class mining approach to profile the distribution of xenobiotic-transforming enzyme homologs in genomes of urinary bacteria. Our analysis revealed a discontinuous distribution of enzyme classes even among closely related organisms. We detected diverse amidase homologs involved in pharmaceutical and dietary additive biotransformation pathways, pinpointing microbial candidates to validate for their involvement in xenobiotic transformations in urine. Overall, we highlight the biocatalytic potential of urinary tract bacteria as a lens to study how the human microbiota may respond and adapt to xenobiotic inputs.