The gut–kidney microbiome–oxalate axis in calcium oxalate nephrolithiasis: mechanisms and microbiome-based interventions

Introduction: Calcium oxalate nephrolithiasis is increasingly recognized as a disorder influencednot only by diet and host oxalate handling, but also by the gut-kidneymicrobiome axis. Emerging multi-omics studies suggest that disturbances inintestinal and urinary microbiota, together with altered microbial metabolites,may contribute to disrupted oxalate homeostasis, inflammatory signaling, epithelialinjury, and crystal retention. Methods: We performed a narrative, semi-structuredreview of PubMed, Embase, and Web of Science (2010-2025), focusing onoxalate metabolism, gut and urinary microbiota, and microbiome-targeted interventionsin nephrolithiasis, with emphasis on calcium oxalate stones. Human andexperimental studies examining microbial composition, microbial metabolites,host transport and genetic determinants, and nutritional or microbial therapieswere qualitatively synthesized. Results: Current evidence indicates that loss of oxalatedegradinggut bacteria and broader dysbiosis are associated with hyperoxaluriaand increased calcium oxalate stone risk, whereas microbiome-supportive dietarypatterns may be protective. Multi-omics analyses reveal coordinated alterationsacross stool, urine, and stone-associated microbiota, implicating pathways involvingshort-chain fatty acids, bile acids, and unconjugated bilirubin in oxalatehandling, inflammation, and lithogenesis. Nutritional modulation may favorablyinfluence this axis, while probiotics, synbiotics, and engineered livebiotherapeutics show encouraging preclinical results. Discussion: Fecal microbiota transplantationremains highly preliminary in this field, and overall human data remainlimited and heterogeneous. The gut-kidney microbiome-oxalate axis providesan integrative framework linking diet, host pathways, microbial metabolites, andmulti-site microbial communities to calcium oxalate nephrolithiasis, and may helpinform future microbiome-based prevention and adjunctive managementstrategies.