A mouse model for the study of diet-induced changes in intestinal microbiome composition on renal calcium oxalate crystal formation.

Abstract

Currently available animal models for calcium oxalate kidney stones are limited in their translational potential. Particularly with increasing interest in gut microbiota involvement in kidney stone disease, there are limited animal models which can be used. As such, we have developed a novel diet-induced hyperoxaluria murine model which addresses some of the shortcomings of other currently available models. Mice C57BL/6 mice were fed a 1.5% sodium oxalate supplemented chow for two weeks and showed no morbidity or mortality. Mice fed the sodium oxalate diet consistently had renal calcium oxalate crystal deposits as confirmed by polarized light microscopy, and energy-dispersive X-ray spectroscopy. We developed a isotope dilution high-performance liquid chromatography/mass spectrometry protocol which confirmed that our model produced both urinary and enteric hyperoxaluria. 16S ribosomal RNA sequencing of stool samples and cecal contents showed that sodium oxalate is a disruptor of the gut microbiome, and may interfere with commensal microbes in the gut microbiome. With consistent results this mouse model is superior to other models of kidney stone disease, as this model can be applied to investigate topics of oxalate absorption, transport, metabolism, excretion, crystal formation, the gut microbiome and testing of various therapeutic agents for translation to early stages of renal crystal formation in kidney stone disease.