N6,N6-Dimethyl-l-Lysine: An Anti-Obesity Metabolite of Lactiplantibacillus plantarum R2-5 From Longevity Area Revealed by Multi-Omics Analysis

Abstract

Lactobacilli bacteria, as probiotics, show significant potential for lipid reduction. Current research into their lipid-lowering effects is in the early stages, with mechanisms largely unexplored. In this study, mice were induced with a high-fat diet (HFD) and treated with Lactiplantibacillus plantarum R2-5 (LPR2-5) via oral gavage. After 12 weeks, the LPR2-5-treated group exhibited substantial improvements in body weight and lipid abnormalities, with significant reductions in liver and abdominal fat accumulation. (LPR2-5 can reduce serum total cholesterol [TC] by 25.7%, lower triglycerides [TG] by 45%, decrease low-density lipoprotein cholesterol [LDL-C] by 30%, and double high-density lipoprotein cholesterol [HDL-C].) Analysis of gut microbiota diversity demonstrated that LPR2-5 intervention altered the gut microbiome, increasing the abundance of short-chain fatty acid (SCFA)-producing bacteria (Lactobacillus, Roseburia) and potentially beneficial microbes (Turicibacter, Christensenella), while inhibiting obesity-associated bacteria (Alistipes, Bilophila), thus altering metabolic activity in the gut. Using multi-omics techniques, key metabolic pathways and metabolites were identified. The lipid-lowering mechanism involved a notable increase in N6,N6-dimethyl-l-lysine, a precursor for carnitine synthesis, enhancing carnitine production in the liver and promoting β-oxidation of long-chain fatty acids, thereby effectively reducing early stage adipose accumulation.