Comprehensive Analysis of Fecal Microbiome and Metabolomics Uncovered dl-Norvaline-Ameliorated Obesity-Associated Disorders in High-Fat Diet-Fed Obese Mice by Targeting the Gut Microbiota

Norvaline is a nonproteinogenic amino acid and an important food ingredient supplement for healthy food. In this study, dl-norvaline administration reduced body weight by more than 40% and improved glucose metabolism and energy metabolism in obese mice induced by a high-fat diet (HFD). Combination analysis of microbiome and metabolomics showed that dl-norvaline supplementation regulated gut bacteria structure, such as increasing beneficial bacteria (Mollicutes_RF39, Ruminococcaceae, Bacteroidaceae, Rikenellaceae, Lactobacillaceae, Clostridiaceae_1, uncultured_bacterium_f_Muribaculaceae, and Rikenellaceae_RC9_gut_group) and decreasing harmful bacteria (Fusobacteriia, Desulfovibrionales, Enterobacteriaceae, Burkholderiaceae, Helicobacteraceae, and Veillonellaceae) and modulated the metabolites involved in arachidonic acid metabolism, thus further promoting short-chain fatty acid production and improving gut barrier, thereby inflammatory responses and oxidative stress were ameliorated. In addition, the pseudogerm-free mouse model verified that dl-norvaline ameliorated obesity-associated disorders in HFD-fed obese mice by targeting gut microbiota. These results clarified that dl-norvaline may be promising for developing and innovating potential functional food products.