Cefazolin shifts the kidney microbiota to promote a lithogenic environment

Abstract

Abstract Clinical studies of the urinary tract microbiome, termed urobiome, suggest a direct, antibiotic-dependent, impact of the urobiome on kidney physiology. However, evidence for kidney bacteria comes from indirect sources or infected tissue. Further, it is unclear how antibiotics impact kidney bacteria. Here we show direct evidence for the presence of bacteria in the kidneys, with microniches in nephrons. In murine kidneys, administration of cefazolin, a commonly used perioperative antibiotic, led to a loss of uroprotective Lactobacillus spp. and proliferation of Enterobacteriaceae (which includes many known uropathogens). This effect was dependent on treatment duration, with recovery post treatment. Uroprotective L. crispatus and a strain of stone-associated E. coli differentially influenced calcium oxalate (CaOx) crystallization through the incorporation of CaOx inhibitors or promoters, respectively. In humans, microbial signatures were identified in the kidney, with unique niches between the glomeruli and tubules, established through RNA sequencing analysis and direct imaging of two independent populations. Collectively, findings support the hypothesis that the kidneys harbor a stable and antibiotic-responsive microbiota that can influence CaOx lithogenesis. The presence of unique, age-dependent microbial signatures in the glomeruli and tubuli carry implications for non-infectious kidney diseases.