Lactiplantibacillus Plantarum YDJ-03 and Limosilactobacillus fermentum YDJ-6 Alleviate Metabolic Syndrome in Mice

Background: Probiotics are increasingly recognized for promoting beneficial effects on intestinal health. However, most probiotic strains have been insufficiently researched, underscoring the need for further studies to fully understand their potential health benefits, especially in metabolic conditions. Therefore, this study aimed to explore the role and possible mechanism of Lactiplantibacillus plantarum YDJ-03 (YDJ-03) and Limosilactobacillus fermentum YDJ-6 (YDJ-6) in metabolic syndrome (MetS) and hyperuricemia. Methods: Twelve mice per group were fed a high-fat, high-fructose, high-cholesterol (HFFC) diet for 90 days. Mice in both the YDJ-03 and YDJ-6 groups were administered a dose of 1.2 × 109 colony-forming units (CFU) intragastrically per mouse for 28 days before being injected with hypoxanthine (400 mg/kg) to induce hyperuricemia. Blood lipids (triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)), liver injury markers (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)), oxidative stress indicators (malondialdehyde (MDA) and superoxide dismutase (SOD)), and renal injury markers (uric acid (UA) and creatinine (CREA)) levels were analyzed after the conclusion of the study. Results: In contrast to the model group, the YDJ-03 group exhibited a marked decrease in liver TGs (p = 0.033), MDA (p = 0.0041), serum UA (p = 0.0071) and CREA (p = 0.0072). The mRNA levels of renal toll-like receptor 2 (Tlr2) (p = 0.0018), tumor necrosis factor receptor-associated factor 6 (Traf6) (p = 0.0013), and nuclear factor kappa B subunit 1 (Nfkb1) (p = 0.032) were downregulated, accompanied by marked attenuation of inflammatory cell infiltration in renal tissues and alleviation of glomerular epithelial cell swelling. Furthermore, YDJ-6 treatment promoted significant downward adjustments in hepatic TG (p = 0.0055), serum TG (p = 0.0082), and LDL-C (p = 0.0233) levels. YDJ-6 treatment also decreased serum ALT (p = 0.0458) and AST (p = 0.029) concentrations, downregulated the gene expression levels of inflammation-related adhesion G protein-coupled receptor E1 (Adgre1) (p = 0.033) and prostaglandin-endoperoxide synthase 2 (Ptgs2) (p = 0.0077), and effectively ameliorated hepatocellular lipid deposition and ballooning degeneration with hepatocyte necrosis. Conclusions: YDJ-03 may exert nephroprotective effects by regulating the TLR2-mediated NF-κB pathway, and YDJ-6 can effectively reduce hepatic fat deposition and inflammation to alleviate liver injury.