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

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.

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.

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.

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.