Compound probiotics alleviate hyperuricemia-induced renal injury via restoring gut microbiota and metabolism.

Abstract

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.