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How gut microbiome correlates with oxalate, butyrate and kidney stones formation Felix, Demian Ferreira

Abstract

Background: Kidney stone disease (KSD) is a worldwide metabolic disorder, that affects about 12% of the world population at some stage of life, representing a financial burden for health systems. The prevalence of urolithiasis is increasing in the past decades, despite progress in the surgical procedures to remove the stones, there is a recurrence rate after the intervention, and there is no definitive cure for it. In the past decades, the role of intestinal microbiota regarding KSD pathology has been gradually unravelled. Oxalate-degrading bacteria and short-chain fatty acid (SCFA) producing microorganisms have been shown to have important roles in crystal formation through direct calcium oxalate breakdown or as inducers of immune responses capable of inhibiting crystal formation in the kidneys. Experimental approach: In order to test the properties of prebiotics in stone formation physiology, we used an in vivo mouse model administering four different formulated diets. A control diet, a sodium oxalate diet to stimulate stone formation, an inulin diet to stimulate SCFA-producing microorganisms, and a tributyrin diet to act as a direct source of butyrate, a specific type of SCFA that we have previously shown to be lacking in kidney stone patients. Results: Results indicated that the sodium oxalate diet reduced the overall mice microbial alpha diversity and the variability of bacterial groups responsible for SCFA production. It also increased oxalate concentrations in the urine and caused crystal formation in the kidney. Furthermore, an inulin diet was able to promote the proliferation of SCFA-related microbiota and SCFA concentrations in the gut, which resulted in reduced oxalate amounts in the urine, therefore, contributing to reducing the risk of stone formation. Tributyrin supplementation did not promote any significant effect. Conclusions: This study corroborates previous research indicating that dietary supplements like inulin are potential prebiotic candidates to promote gut homeostasis, oxalate absorption regulation, and modulate SCFA-related microbial population and SCFA production in the intestine.

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