Extensive research has explored how Chinese herbal formulations may slow the advancement of chronic kidney disease (CKD) by modulating colonic microflora and microbiota-derived metabolites. Despite this, it remains unclear whether FuZhengHuaYuJiangZhuTongLuo (FZHY) exerts regulatory effects on CKD that parallel those reported for AST-120.To address this question, we systematically compared the influence of FZHY and AST-120 on gut microbiota composition and plasma metabolomic profiles in a chronic kidney disease model. A unilateral ureteral obstruction (UUO)-induced CKD rat model was established, after which the animals received either FZHY or AST-120. Plasma, stool, and kidney samples were subsequently evaluated using non-targeted LC-MS metabolomics, 16S rRNA sequencing, and histopathological assessment. Correlation networks linking bacterial candidates with key metabolites were also constructed. Both interventions markedly mitigated UUO-associated renal dysfunction and fibrosis while reshaping microbial communities and metabolic signatures. Relative to the untreated UUO group, FZHY administration increased the abundance of p_Firmicutes and o_Peptostreptococcales_Tissierellales, accompanied by the upregulation of 14 negative-ion and 40 positive-ion metabolites and the downregulation of 21 and 63 metabolites, respectively. In contrast, AST-120 supplementation elevated g_Prevotellaceae_NK3B31_group and f_Prevotellaceae, and altered 12 negative-ion metabolites upward and 23 downward, along with 56 positive-ion metabolites upregulated and 63 downregulated. Furthermore, FZHY enhanced bacterial biomarkers that showed negative correlations with harmful metabolites such as 4-hydroxyretinoic acid and positive correlations with beneficial ones like L-arginine. AST-120 enriched bacterial biomarkers inversely associated with toxic compounds including glycoursodeoxycholic acid, 4-ethylphenol, and indole-3-acetic acid.Both FZHY and AST-120 alleviated renal injury in the UUO-induced CKD model, potentially through restoration of disrupted microbial and metabolic pathways. Because each treatment modulated distinct bacterial taxa and metabolites, FZHY may serve as a valuable complementary therapeutic strategy alongside AST-120 in CKD management.
