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Background <p>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.</p> Results <p>We developed a novel synbiotic formulation containing <i>Lactiplantibacillus plantarum</i>, <i>Lacticaseibacillus casei</i>, <i>Bifidobacterium breve</i>, 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 <i>Prevotellaceae_Ga6A1_group</i>, <i>UCG_009</i>, <i>Candidatus_Saccharimonas</i>, <i>Prevotellaceae_UCG_001</i> and <i>Phascolarctobacterium</i>. Furthermore, synbiotic supplementation reduced systemic oxalate overload by alleviating intestinal barrier damage and modulating mucosal oxalate transporter expression.</p> Conclusion <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月21日

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  • Xian-Miao Li,
  • Yirixiatijiang Amier,
  • Wen-Long Wan,
  • Yong-Qi Wang,
  • Guo-Rui-Yu Lyu,
  • Jun-Lin Lu,
  • Jing-Yi Rao,
  • Yuan-Yuan Yang,
  • Yang Xun,
  • Xiao Yu

摘要

Background

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.

Results

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.

Conclusion

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.