Kidney stone formation and the gut microbiome are altered by antibiotics in genetic hypercalciuric stone-forming rats
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ORIGINAL PAPER
Kidney stone formation and the gut microbiome are altered by antibiotics in genetic hypercalciuric stone‑forming rats Joshua M. Stern1 · Robert D. Burk1 · John Asplin2 · Nancy S. Krieger3 · Sylvia O. Suadicani1 · Yi Wang1 · Mykhaylo Usyk1 · Justin A. Lee1 · Luojing Chen3 · Jennifer Becker3 · Michaela Chan3 · David A. Bushinsky3 Received: 10 June 2020 / Accepted: 21 October 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Gut microbiome · Kidney stone · Urinary stone disease · Antibiotics
Introduction Urinary stone disease (USD) is a growing public health burden in the United States with a ~ 70% increase in prevalence over the last 30 years [1]. USD is associated with increased risks of kidney function loss [2], heart disease [3], bone fracture [4] and asthma [5, 6] that results in annual healthcare costs exceeding $10 billion [1]. In the last 30 years, no new medication has been advanced to prevent calcium stone disease.
* Joshua M. Stern [email protected] 1
Albert Einstein College of Medicine, 1300 Morris Park Ave. Bronx, New York, NY 10461, USA
2
Litholink, Laboratory Corporation of America® Holdings, Chicago, IL, USA
3
University of Rochester, Rochester, NY, USA
Manipulation of the gut flora is increasingly being recognized as a means to improve human health, with rodent models representing an invaluable tool to study the host–microbio
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