Preventive Effects of <i>Lactobacillus</i> Mixture against Chronic Kidney Disease Progression through Enhancement of Beneficial Bacteria and Downregulation of Gut-Derived Uremic Toxins

Abstract

Gut dysbiosis is a major contributor to adverse chronic kidney disease (CKD) progression, and microbiota-based strategies could be considered as a novel therapeutic and preventative target. In this study, a probiotic screening platform based on gut-derived uremic toxin-reducing probiotics was developed and the underlying mechanism was further verified through a 0.2% adenine-induced CKD mouse model. Two strains (<i>Lactobacillus paracasei</i> and <i>Lactobacillus plantarum</i>) were selected due to their high clearance ability and named <i>Lactobacillus</i> mix (Lm). The results showed that Lm significantly improved the kidney function by reducing kidney injury and fibrotic-related proteins. Furthermore, Lm decreased oxidative stress and proinflammatory reactions and elevated immune responses in the kidney. Importantly, Lm reversed gut dysbiosis and restored the abundance of commensal bacteria, especially short-chain fatty acid producers, leading to improved intestinal barrier integrity <i>via</i> modulation of microbial composition and metabolite production. Taken together, these findings provided evidence that Lm could be a preventive approach against CKD.