Liu Ping, Hu Ping, Jin Meiping, Sun Weiqian, Wu Jiajun, Tang Yuyan, Shi Danye, Xie Ting, Tong Yijing, Huang Lusheng, Zhang Dongliang, Zheng Hui, Xu Xudong, He Haidong
Division of Nephrology, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai, 201199, China.
Division of Endocrinology, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Shanghai, 201199, China.
BMC Microbiol. 2025 May 8;25(1):280. doi: 10.1186/s12866-025-04012-5.
To investigate the role and mechanisms of gut microbiota in hyperuricemia-induced renal injury, we established renal failure models using unilateral nephrectomized mice. After four weeks of adenine and potassium oxalate-supplemented diet, probiotic intervention was administered. Renal pathological and functional changes were assessed through H&E staining and plasma biochemical analysis. Gut microbiota composition and metabolite profiles were evaluated using 16 S rRNA gene sequencing and non-targeted metabolomics of fecal samples.Our findings demonstrate that the compound probioticS effectively attenuated hyperuricemia-associated renal dysfunction and interstitial fibrosis. The intervention reduced oxidative stress, mitophagy, and apoptosis in renal tubules. Probiotic treatment enhanced gut microbiota diversity, notably increasing the abundance of Prevotella_9, Dorea, and unclassified Bacteroidota, while decreasing unclassified Desulfovibrio. KEGG enrichment analysis revealed that probiotic intervention upregulated arginine and proline metabolism, as well as tyrosine metabolism in feces. Furthermore, it enhanced the metabolism of arginine, proline, valine, leucine, and isoleucine in plasma.Notably, sulfocholic acid and urocanic acid showed negative correlations with oxidative stress markers, autophagy, and apoptosis indicators. Similarly, plasma L-proline levels were inversely correlated with these pathological parameters.These results suggest that the compound probiotics may mitigate hyperuricemia-induced kidney damage through restoration of gut microbiota homeostasis and preservation of plasma and fecal metabolites. The protective mechanisms likely involve attenuation of hyperuricemia-associated oxidative stress, mitochondrial dysregulation, and phagocytosis-induced apoptosis.Our study provides compelling evidence that probiotic supplementation represents a promising therapeutic strategy for hyperuricemia-induced renal injury, potentially through modulation of gut microbiota and associated metabolic pathways.
为了研究肠道微生物群在高尿酸血症诱导的肾损伤中的作用及机制，我们使用单侧肾切除的小鼠建立了肾衰竭模型。在给予含腺嘌呤和草酸钾的饮食四周后，进行益生菌干预。通过苏木精-伊红（H&E）染色和血浆生化分析评估肾脏病理和功能变化。使用16S rRNA基因测序和粪便样本的非靶向代谢组学评估肠道微生物群组成和代谢物谱。我们的研究结果表明，复合益生菌有效地减轻了高尿酸血症相关的肾功能障碍和间质纤维化。该干预降低了肾小管中的氧化应激、线粒体自噬和细胞凋亡。益生菌治疗提高了肠道微生物群的多样性，显著增加了普雷沃氏菌属_9、多雷氏菌属和未分类拟杆菌门的丰度，同时降低了未分类脱硫弧菌属的丰度。京都基因与基因组百科全书（KEGG）富集分析显示，益生菌干预上调了粪便中的精氨酸和脯氨酸代谢以及酪氨酸代谢。此外，它增强了血浆中精氨酸、脯氨酸、缬氨酸、亮氨酸和异亮氨酸的代谢。值得注意的是，牛磺胆酸和尿刊酸与氧化应激标志物、自噬和凋亡指标呈负相关。同样，血浆L-脯氨酸水平与这些病理参数呈负相关。这些结果表明，复合益生菌可能通过恢复肠道微生物群稳态以及维持血浆和粪便代谢物来减轻高尿酸血症诱导的肾损伤。其保护机制可能包括减轻高尿酸血症相关的氧化应激、线粒体失调和吞噬作用诱导的细胞凋亡。我们的研究提供了有力证据，表明补充益生菌是治疗高尿酸血症诱导的肾损伤的一种有前景的治疗策略，可能是通过调节肠道微生物群及相关代谢途径来实现。
