A novel synbiotic formulation prevents calcium oxalate stones by restoring gut microbiota homeostasis

Calcium oxalate (CaOx) nephrolithiasis, a highly prevalent renal disorder, underscores an urgent demand for novel therapeutic strategies to prevent stone formation. Accumulating evidence has elucidated a robust link between renal CaOx stone formation and gut microbiota dysbiosis, suggesting microbial modulation as a potential therapeutic target. Recently, microbiome-targeted interventions, particularly synbiotic formulations, have demonstrated promising therapeutic efficacy in mitigating hyperoxaluria and preventing renal stone formation.

We developed a novel synbiotic formulation containing Lactiplantibacillus plantarum, Lacticaseibacillus casei, Bifidobacterium breve, and prebiotic galactooligosaccharides (GOS). Subsequently, the synbiotic or its individual components (multi-strain probiotic mixture or GOS) were administered to ethylene glycol (EG)-induced hyperoxaluric rats via daily oral gavage for 28 days. We found that the synbiotic formulation exhibited superior anti-nephrolithic activity compared to the multi-strain probiotic mixture or GOS alone, attributable to the synergistic effects of probiotic-prebiotic combinations. Remarkably, synbiotic supplementation not only significantly reversed the EG-induced reductions in gut microbiota richness and evenness, but also restored the microbiota architecture. Additionally, a significant increase was observed in the relative abundance of multiple beneficial genera implicated in short-chain fatty acids (SCFAs) production, including Prevotellaceae_Ga6A1_group, UCG_009, Candidatus_Saccharimonas, Prevotellaceae_UCG_001 and Phascolarctobacterium. Furthermore, synbiotic supplementation reduced systemic oxalate overload by alleviating intestinal barrier damage and modulating mucosal oxalate transporter expression.

Our findings demonstrate that synbiotic intervention effectively reverses EG-induced hyperoxaluria by reversing gut microbiota dysbiosis to modulate oxalate homeostasis. Thus, this study not only proposes a synbiotic formulation for nephrolithiasis prevention but also elucidates its mechanistic basis, offering potential therapeutic advancements in disease management.