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Kidney stone formation and the gut microbiome are altered by antibiotics in genetic hypercalciuric stone-forming rats

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Abstract

Antibiotics can alter the gut microbiome (GMB), which may be associated with stone disease. We sought to determine the effect that antibiotics have on the GMB, urine ion excretion and stone formation in genetic hypercalciuric stone-forming (GHS) rats. 116th generation GHS rats were fed a fixed amount of a normal calcium (1.2%) and phosphate (0.65%) diet, and divided into three groups (n = 10): control (CTL) diet, or supplemented with ciprofloxacin (Cipro, 5 mg/day) or Bactrim (250 mg/day). Urine and fecal pellets were collected over 6, 12 and 18 weeks. Fecal DNA was amplified across the 16S rRNA V4 region. At 18 weeks, kidney stone formation was visualized by Faxitron and blindly assessed by three investigators. After 18 weeks, urine calcium and oxalate decreased with Bactrim compared to CTL and Cipro. Urine pH increased with Bactrim compared to CTL and Cipro. Urine citrate increased with Cipro compared to CTL and decreased by half with Bactrim. Calcification increased with Bactrim compared to CTL and Cipro. Increased microbial diversity correlated with decreased urinary oxalate in all animals (R = − 0.46, p = 0.006). A potential microbial network emerged as significantly associated with shifts in urinary pH. Bactrim and Cipro differentially altered the GMB of GHS rats. The Bactrim group experienced a decrease in urine calcium, increased CaP supersaturation and increased calcification. The GMB is likely a contributing factor to changes in urine chemistry, supersaturation and stone risk. Further investigation is required to fully understand the association between antibiotics, the GMB and kidney stone formation.

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Funding

David A. Bushinsky is supported by NIH (RO1 DK075462). Joshua M. Stern is supported by The Complications of Diabetes Consortium (DIACOMP) and the Mouse Microbiome Metabolic Research Program (MMRP).

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Authors and Affiliations

  1. Albert Einstein College of Medicine, 1300 Morris Park Ave. Bronx, New York, NY, 10461, USA

    Joshua M. Stern, Robert D. Burk, Sylvia O. Suadicani, Yi Wang, Mykhaylo Usyk & Justin A. Lee

  2. Litholink, Laboratory Corporation of America® Holdings, Chicago, IL, USA

    John Asplin

  3. University of Rochester, Rochester, NY, USA

    Nancy S. Krieger, Luojing Chen, Jennifer Becker, Michaela Chan & David A. Bushinsky

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  1. Joshua M. Stern
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Correspondence to Joshua M. Stern.

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Stern, J.M., Burk, R.D., Asplin, J. et al. Kidney stone formation and the gut microbiome are altered by antibiotics in genetic hypercalciuric stone-forming rats. Urolithiasis 49, 185–193 (2021). https://doi.org/10.1007/s00240-020-01223-5

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