Alteration of Gut Microbiome in Kidney injury caused by hyperuricemia
Background:Hyperuricemia(HUA) induced renal damage has become a serious public health problem. The imbalance of intestinal flora is one of the main factors causing HUA and chronic kidney disease (CKD). However, the precise role of intestinal flora and metabolites in the development of nephropathy caused by HUA in CKD remains uncertain.Methods:In this study, we established a mouse model of hyperuricemia-associated renal injury in the context of CKD by feeding unilateral nephrectomy mice with adenine and potassium oxoate for 4 weeks. H&amp;E staining combined with plasma biochemistry was used to monitor the pathological and functional changes of the kidneys.We employed 16S rRNA gene sequencing to identify fecal microorganisms and non-targeted metabolomics to analyze changes in fecal and plasma metabolites. Additionally, we conducted correlation analysis between differential flora and metabolites.Result:The abundance of genera including Monoglobus, Akkermansia, Eubacterium_xylanophilum_group, RF39 unclassified, UCG-005, Lachnospiraceae, NK4A136_groupg, and Ruminococcus was significantly lower both in UNCL and model group compared to sham group.KEGG enrichment analysis revealed significant differences in the metabolic pathways of fecal metabolites between the sham and model groups. Specifically, the metabolites were found to be primarily associated with histidine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, as well as tyrosine metabolism.The plasma differential metabolites primarily participate in various metabolic pathways, including aminoacyl tRNA biosynthesis, glycine, serine, and threonine amino acid metabolism, valine, leucine, and isoleucine biosynthesis, tyrosine biosynthesis metabolism, biotin metabolism, and taurine and hypotaurine metabolism. Akkermansia, Lactobacillus, UCG-005, Bacteroides, and Eubacterium_xylanophilum_group were found to have a positive correlation with the metabolism of tyrosine, leucine, isoleucine, glycine, serine, and threonine.Conclusion:Hyperuricemia-related renal injury in the context of CKD is associated with changes in intestinal flora, feces, and plasma metabolites. These alterations in flora and metabolite pathways are believed to play a role in the development of uric acid nephropathy. Investigating these pathways may offer potential for new therapeutic interventions.