The application of metabolites derived from gut microbiota to the treatment of chronic kidney disease: a network pharmacology study

BACKGROUND: Chronic kidney disease (CKD) has emerged as a significant global health challenge. Gut microbiota metabolites microbiota can exert favorable effects on CKD. But their underlying mechanisms are not fully elucidated. The aim of this study is to investigate the protective mechanism of gut microbiota metabolites in CKD via network pharmacology study. METHODS: The targets of gut microbiota metabolites were acquired from Similarity Ensemble Approach and Swiss Target Prediction. The CKD targets were acquired from disease database. The protein-protein interaction (PPI) networks, gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were conducted to identify core target and key signaling pathway. The "gut microbiota-targets-metabolites" was built to screen the core metabolites. Molecular docking was employed to measure the binding affinity. RESULTS: A total of four targets were considered core targets between gut microbiota metabolites and CKD. The GO results indicated that the biological function of metabolites was associated with the regulation of fatty acid metabolic process, and KEGG pathway enrichment revealed that the PI3K/AKT signaling pathway was closely involved in the regulation of CKD by gut microbiota metabolites. The network analysis revealed that butyrate, equol, 3-indolepropionic acid, and propionate were the core gut microbiota metabolites. The molecular docking results indicated their good binding affinity to the core targets. CONCLUSION: The gut microbiota metabolites exert beneficial effect on CKD by regulating multi-signaling pathway and multi-targets. This work provides a scientific support for the application of gut microbiota metabolites to CKD treatment.