Unveiling the mechanism of metabolites derived from gut microbiota in the treatment of acute kidney injury via network pharmacology and bioinformatics

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Abstract Background Acute kidney injury (AKI) affects a considerable proportion of patients that represents a major challenge for clinical treatment. Gut microbiota metabolites have been reported to attenuate acute kidney injury (AKI), yet their underlying mechanisms remain largely elusive. The present study aimed to explore the protective mechanisms of these metabolites against AKI using. Methods The targets of metabolites and AKI were obtained from public databases. The PPI network is utilized to identify the core targets. GO and KEGG enrichment analysis were employed to predict significant pathway and biological functions. The Gut-Metabolites-Targets-Pathway network (G-M-T-P) network was constructed to screen the core metabolites. Furthermore, molecular docking was applied to evaluate the binding affinities between the metabolites and their candidate targets. Results A total of 84 overlapping targets between gut microbiota metabolites and AKI were acquired. The beneficial effects of gut microbiota metabolites were associated with the regulation of inflammatory response and hypoxia. HIF-1 pathway was identified as the significant pathway mediating the effects of metabolites. STAT3, HIF1A, NFKB1, IL6 and AKT1 were identified as the core therapeutic targets of metabolites against AKI. The G-M-T-P network identified acetate, butyrate, propionate, and 3-indolepropionic acid as the core metabolites. The core metabolites exhibited strong affinity binding affinity for the core targets, suggesting their potential application in candidate drug development. Conclusion The study highlights that the promising effects of gut microbiota metabolites in AKI treatment through modulating multi targets and pathways.