Dietary Fermented Soy Extract and Active Lactic Acid Alleviate Chronic Kidney Disease in Mice via Inhibition of Inflammation and Modulation of Gut Microbiota (FS15-07-19)

Chronic kidney disease (CKD) is a global epidemic and posing serious health problems with an increasing prevalence worldwide. Effective preventive strategies are urgently needed. This study was conducted to investigate the effect of a fermented soybean product (ImmunBalance, IMB) and active lactic acid (ALA) on adenine-induced CKD in mice. Female C57BL/6 mice were randomly assigned into one of the following experimental groups: negative control (NC), model control (MC), models with oral gavage of IMB at 250 (IMB-L) or 1000 mg/kg BW (IMB-H), ALA at 1000 (ALA-L) or 2000 mg/kg BW (ALA-H). The CKD model was established by ip. injection of adenine daily for 4 weeks, and treatments started the same day as adenine injection till for 8 weeks. The kidney histopathology was evaluated by H&E staining. Blood cytokines and kidney injury biomarkers were measured by Multiplex sandwich immunoassays. Expression of cytokines and stem cells-related genes in kidney was analyzed by quantitative real-time PCR. The levels of major phyla of gut microbiota were quantified by quantitative PCR. The CKD mice showed obvious tubular dilation, tubulointerstitium degeneration or atrophy, interstitial chronic and acute inflammation. The administration of IMB and ALA significantly improved histopathological damages. Both of IMB and ALA decreased serum levels of cytokines and kidney toxicity biomarkers MCP-1, IL-6, IP-10, TIMP-1, Cystatin C and Clusterin, and the mRNA levels of inflammatory biomarkers IL-6, IL-1β, TGF-β1, TLR-4, F4/80 and TNF-α in kidney samples. CKD increased gene expression levels of stem cell biomarkers in kidney, which were reduced by IMB or ALA treatment. CKD reduced gut Clostridium leptumb level that was significantly increased by IMB or ALA treatment. Our results suggest that dietary supplementation of IMB or ALA may significantly delay the development and progression of CKD. Nichimo Biotics Co., Ltd and Lifetrade Co. Ltd, Japan.