Hippuric acid metabolism by Corynebacteriumglucuronolyticum-like bacteria promotes calcium oxalate crystallization

Nephrolithiasis (kidney stone disease) incidence is rising, and microbes have been implicated in kidney stone formation, yet the underlying mechanisms remain incompletely defined. Here, urinary microbiome analysis reveals enrichment of Corynebacterium glucuronolyticum-like (C. glucuronolyticum-like) bacteria in calcium oxalate (CaOx) stone patients. In vivo and in vitro experiments suggest that C. glucuronolyticum-like bacteria promote CaOx crystal nucleation and aggregation in experimental models. Mechanistically, hippuric acid (HA) is identified as a key urinary anti-crystallization metabolite. C. glucuronolyticum-like bacteria degrade HA by expressing HA hydrolase, thereby accelerating crystal nucleation, while biofilm formation accelerates crystal aggregation. C. glucuronolyticum-like bacteria exhibit multidrug resistance, and even effective antibiotics show poor efficacy. However, HA supplementation or cranberry-derived diets attenuate C. glucuronolyticum-like bacteria-associated CaOx crystallization in experimental models. These findings suggest that C. glucuronolyticum-like bacteria contribute to CaOx crystallization through metabolic regulation and biofilm assembly, highlighting C. glucuronolyticum-like bacteria and HA hydrolase as therapeutic targets.