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Abstract: TH-PO560

Antibiotics Affect the Intestinal Microbiome and Alter Kidney Stone Formation in Genetic Hypercalciuric Stone-Forming Rats

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Authors

  • Stern, Joshua M., Albert Einstein Medical School, Montefiore Medical Center, New York, New York, United States
  • Krieger, Nancy S., University of Rochester Medical School, Rochester, New York, United States
  • Asplin, John R., Litholink Corporation, Chicago, Illinois, United States
  • Granja, Ignacio, Litholink Corporation, Chicago, Illinois, United States
  • Suadicani, Sylvia O., Albert Einstein Medical School, Montefiore Medical Center, New York, New York, United States
  • Chen, Luojing, University of Rochester Medical School, Rochester, New York, United States
  • Becker, Jennifer, University of Rochester Medical School, Rochester, New York, United States
  • Chan, Michaela, University of Rochester Medical School, Rochester, New York, United States
  • Bushinsky, David A., University of Rochester Medical School, Rochester, New York, United States
Background

There is growing evidence that antibiotic exposure is associated with incident stone disease. The intestinal microbiome (IMB) can rapidly shift in response to outside stimuli such as antibiotics. We utilized genetic hypercalciuric stone-forming (GHS) rats, whose pathophysiology parallels that of human hypercalciuria and who spontaneously form calcium phosphate (CaP) stones, to determine the effect of antibiotics on the intestinal microbiome, urine ion excretion and stone formation.

Methods

116th generation GHS rats were fed a fixed amount of a normal Ca (1.2%) and P (0.65%) diet, housed in metabolic cages and divided into 3 groups (n=10): control (CTL) diet, or supplemented with ciprofloxacin (Cipro, 5 mg/d) or Bactrim (250 mg/d). Urine and fecal pellets were collected at 6, 12 and 18 wks for analyses. Fresh fecal pellets were stored at -80oC and then prepared for analysis by DNA extraction and amplification of the 16S rRNA V4 region using barcoded primers on an Illumina platform. QIIME was used for analysis. At 18 wks kidney stone formation was determined by Faxitron analysis and assessed by 3 blinded reviewers.

Results

After 18 wks, urine Ca decreased with Bactrim (CTL=13.7± 0.4, Bactrim=12.1±0.4 mg/d, p<0.05) as did urine oxalate (CTL=1.2±0.04, Bactrim=0.8±0.02 mg/d, p<0.05). CaP supersaturation increased with Bactrim (CTL=6.8±0.4, Bactrim=8.4±0.5, p<0.05) while CaOx supersaturation fell (CTL=16.2± 0.6, Bactrim=12.0±0.4, p<0.05). Calcification was increased by Bactrim (CTL=1.0±0.2, Bactrim=2.98±0.3, p<0.05). Cipro was not different from CTL for any parameter. Analysis of the GHS IMB shifted substantially and principal component analysis showed the Bactrim group and controls clustered separately (p=0.001). Microbial diversity negatively correlated with urinary oxalate in all animals (R=-0.46, p=0.006), and positively correlated with urinary pH in the Bactrim treated group (R=0.76, p=0.01).

Conclusion

Bactrim altered the IMB of GHS rats and also caused a fall in urine Ca, increased CaP supersaturation and increased calcification while Cipro did not change urine ion excretion or calcification. Whether the alteration in the IMB is mechanistically related to the changes in urine ion excretion and calcification remains to be determined.

Funding

  • NIDDK Support