The Gut-Kidney Axis in Calcium Oxalate Nephrolithiasis: Nutritional and Microbial Insights

Abstract

Calcium oxalate (CaOx) nephrolithiasis is the most common type of kidney stone disease worldwide. Recent studies show that its development cannot be explained solely by renal solute handling; instead, it reflects a broader interaction between dietary habits, the intestinal microbiota, and host metabolic responses. Intestinal absorption of calcium and oxalate-two central drivers of lithogenesis-is shaped by both microbial composition and dietary patterns. Although Oxalobacter formigenes was initially regarded as the main oxalate-degrading organism, newer studies indicate that a wider disturbance of the gut microbiota, especially the loss of short-chain fatty acid (SCFA)-producing species, may increase susceptibility to stone formation. In this review, nutritional, microbial, and mechanistic evidence is brought together to examine how diet-particularly salt, animal protein, calcium, oxalate, fruits, vegetables, and water intake-modulates the gut-kidney axis. Diets high in salt or animal protein tend to shift the microbiota toward more pro-inflammatory and acidogenic profiles, while fiber-rich, plant-based diets and adequate hydration appear to support microbial diversity, SCFA production, and epithelial barrier integrity. Probiotic and synbiotic interventions have also gained attention as potential strategies to reduce stone recurrence by targeting gut microbial function. Taken together, current findings suggest that the gut-kidney axis is a dynamic metabolic link between diet, microbial ecology, and renal physiology. Future studies combining multi-omics methods with personalized nutritional approaches may help develop more effective microbiota-based prevention and treatment strategies for CaOx nephrolithiasis.