Abstract: TH-PO1084

An Association between the Genetic Hypercalciuric Stone-Forming Rat and the Gut Microbiome

Session Information

Category: Mineral Disease

  • 1204 Mineral Disease: Nephrolithiasis

Authors

  • Stern, Joshua M., Albert Einstein College of Medicine , Bronx, New York, United States
  • Krieger, Nancy S., Univ. of Rochester, Rochester, New York, United States
  • Abramowitz, Matthew K., Albert Einstein College of Medicine, New York, New York, United States
  • Bushinsky, David A., University of Rochester Medical Center, Rochester, New York, United States
Background

The Genetic Hypercalciuric Stone-forming (GHS) rat has been an established model of kidney stone disease. The rats have been selectively inbred for hypercalciuria for over 100 generations, originally from standard Sprague Dawley (SD) rats. All GHS rats make stones by 18 weeks of age. The model has been extensively studied and phenotyped. However, no study has previously examined differences in the rat's microbiome. In this study we characterize the gut microbiome (GMB) from GHS rats compared to age and sex matched SD controls.

Methods

4 male GHS rats and 2 male SD rats were housed separately and fed similar diets of rat chow in the same animal room. Fresh fecal pellets were collected at one single time point, stored at -80oC and sent to the Albert Einstein Department of Urology where the pellets were prepared for analysis by DNA extraction, amplification of the 16S rRNA V4 region using barcoded primers on an Illumina platform. QIIME was used for analyses.

Results

16S rRNA analysis between the 2 groups found significant differences. Bacteriodes genus was 39% more abundant in the GHS. Firmicutes Phylum was 17.2% more abundant in the SD rats as compared to 5.7% in the GHS rats, a 67% increase in the SD rats. The alpha diversity of the GHS rats’ GMB cluster well and are widely separated from SD. The GHS rats have a lower Shannon score diversity. Roseburia genus, known to contain species that produce beneficial short chain fatty acids was 70% more abundant in the SD group. Similarly Faecalibacterium genus, with known butyrate producers, was increased 35% in the SD rats.

Conclusion

We, for the first time, demonstrate that age and sex matched GHS rats carry a GMB that is distinct from its SD ancestors. Of particular interest is the decreased bacterial diversity seen in these rats at just 12 weeks of age. Bacteroides genera is significantly up-regulated in the GHS rats and similar to findings seen in human stone formers (Stern et al., Urolithiasis 44:399, 2016). Future studies to determine causality and directionality of this effect are warranted.

Funding

  • Private Foundation Support