Probiotic mixture ameliorates cisplatin-induced kidney injury by reducing uremic toxins and modulating the gut microbiota.

AIMS: Increasing evidence on the gut-kidney axis has highlighted the critical role of the gut microbiota in maintaining renal function. This study investigated the protective effects of a probiotic mixture (PM) in a cisplatin-induced kidney injury model and explored its potential mechanisms through modulation of uremic toxins and gut microbiota composition. MATERIALS AND METHODS: Probiotic strains were initially evaluated for their ability to remove indole, a microbial precursor of the uremic toxin indoxyl sulfate (IS). The renoprotective effects of individual strains and a composite probiotic formulation were then compared in a cisplatin-induced animal model. Changes in gut microbiota composition following administration of the composite formulation were analyzed, and correlation analyses were performed between microbial profiles and biomarkers of renal injury. KEY FINDINGS: The selected probiotic strains exhibited significantly greater indole removal capacity in vitro with day-3 reductions of 49.3-87.7%. In vivo, administration of the composite probiotic formulation attenuated cisplatin-induced body weight loss, hepatic injury, and renal dysfunction. These protective effects were accompanied by alterations in gut microbiota composition and reduced circulating uremic toxins. Cisplatin increased serum IS and p-cresyl sulfate (pCS) concentrations by approximately 5- and 13-fold, respectively, whereas probiotic treatment significantly attenuated both increases. Correlation analysis revealed associations between specific microbial taxa and renal injury biomarkers. SIGNIFICANCE: These findings suggest that probiotic supplementation may exert renoprotective effects by reducing gut-derived uremic toxins and modulating the gut microbiota. Targeting the gut-kidney axis through probiotic intervention may represent an adjunctive strategy for preventing cisplatin-induced nephrotoxicity.