Login to Access Video or Poster Abstract: MP12-13
Sources of Funding: University of Florida Department of Urology

Introduction

Nephrolithiasis afflicts 1 in every 11 Americans, causing severe renal pain and reduction in quality of life. A majority of nephrolithiasis patients exhibit absorptive hypercalciuria (AH), a metabolic defect where intestinal absorption of dietary calcium is abnormally high. Prior genetics studies have not yielded a mechanism for this metabolic defect. Since there is a diverse microbial community in the human intestinal tract, with poorly defined effects on systemic health, we hypothesize that AH is mediated by changes in the intestinal microbial community that increase calcium absorption by intestinal epithelium. We test this by characterizing the urine chemistry and gut microbiota changes that occur in a rodent model upon administration of high doses of oral antibiotics.

Methods

6 week-old male and female Sprague-Dawley rats were evenly distributed in the following groups: control (n=12), chloramphenicol-treated (n=12) and neomycin-treated (n=12). All rats underwent pre-treatment urine and stool collection. Subsequently, control rats were provided sterile water ad libitum for 7 days; chloramphenicol and neomycin-treated rats received sterile water (ad libitum) containing 0.07% of their respective antibiotics for 7 days. Rats underwent post-treatment urine and stool collection. Pre- and post-treatment urinary calcium was assessed. Alterations in intestinal microbiota were characterized using 16S rRNA Illumina paired-end sequencing, followed by custom principal components analyses.

Results

Gut microbial community structure was markedly different in both antibiotic treatment groups, compared to controls. Directly following antibiotic administration, neomycin-treated rats were colonized by high numbers of Sphingomonas species and showed a loss in Lactobacillus species; chloramphenicol-treated rats were highly colonized by Klebsiella species. Urinary calcium increased in both antibiotic treatment groups, and was most pronounced immediately after antibiotic administration.

Conclusions

Treatment with either neomycin or chloramphenicol significantly altered the gut microbiome compared to control rats. This is consistent with classical studies that suggested intestinal microbes may impact nutrient absorption, and that use of oral antibiotics may alter urinary concentrations of calcium. These data indicate that we have designed a model in which to further test the role of gut microbiota in modulating urinary calcium, and may provide a path to novel therapies for nephrolithiasis patients.

Funding

University of Florida Department of Urology