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A mouse model for the study of diet-induced changes in intestinal microbiome composition on renal calcium oxalate
Sarah Hanstock1, Demian Ferreira1, Hans Adomat1
1The Stone Centre at Vancouver General Hospital, Department of Urologic Sciences, University of British Columbia, Jack Bell Research Centre, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
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. 16 S 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.
Insights
Researchers developed a new mouse model for calcium oxalate kidney stones. This diet-induced hyperoxaluria model effectively mimics stone formation and gut microbiome changes, aiding research into kidney stone disease.
Area of Science:
- Nephrology
- Microbiology
- Animal Models
Background:
- Existing animal models for kidney stones have limited translational value, especially for studying gut microbiota's role.
- There is a need for better models to investigate kidney stone disease mechanisms.
Purpose of the Study:
- To develop and validate a novel diet-induced hyperoxaluria murine model.
- To assess the model's utility in studying oxalate metabolism, gut microbiome alterations, and therapeutic interventions.
Main Methods:
- C57BL/6 mice were fed a 1.5% sodium oxalate supplemented diet for two weeks.
- Renal calcium oxalate deposits were confirmed using polarized light microscopy and energy-dispersive X-ray spectroscopy.
- Urinary and enteric hyperoxaluria were quantified using isotope dilution high-performance liquid chromatography/mass spectrometry.
- Gut microbiome changes were analyzed via 16S ribosomal RNA sequencing of stool and cecal samples.
Main Results:
- The diet induced hyperoxaluria without causing morbidity or mortality.
- Consistent renal calcium oxalate crystal deposits were observed.
- The model demonstrated both urinary and enteric hyperoxaluria.
- Sodium oxalate disrupted the gut microbiome composition and interfered with commensal microbes.
Conclusions:
- This novel murine model provides a robust platform for studying kidney stone disease.
- The model is suitable for investigating oxalate transport, metabolism, gut microbiome interactions, and testing therapeutic agents.
- It offers a valuable tool for advancing research in early-stage renal crystal formation.
