MP12-13 A RAT MODEL TO STUDY THE ROLE OF GUT BACTERIA IN REGULATION OF URINARY CALCIUM

Abstract

You have accessJournal of UrologyStone Disease: Basic Research & Pathophysiology I1 Apr 2017MP12-13 A RAT MODEL TO STUDY THE ROLE OF GUT BACTERIA IN REGULATION OF URINARY CALCIUM Ryan Chastain-Gross, Pedro Espino-Grosso, Paul Dominguez-Gutierrez, John Asplin, Vincent Bird, Saeed Khan, and Benjamin Canales Ryan Chastain-GrossRyan Chastain-Gross More articles by this author , Pedro Espino-GrossoPedro Espino-Grosso More articles by this author , Paul Dominguez-GutierrezPaul Dominguez-Gutierrez More articles by this author , John AsplinJohn Asplin More articles by this author , Vincent BirdVincent Bird More articles by this author , Saeed KhanSaeed Khan More articles by this author , and Benjamin CanalesBenjamin Canales More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.435AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES 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. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e149 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Ryan Chastain-Gross More articles by this author Pedro Espino-Grosso More articles by this author Paul Dominguez-Gutierrez More articles by this author John Asplin More articles by this author Vincent Bird More articles by this author Saeed Khan More articles by this author Benjamin Canales More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...