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.
Fecal microbiota transplantation (FMT) could significantly alter the recipient's gut bacteria composition and attenuate obesity and obesity-related metabolic syndromes. DL-norvaline is a nonproteinogenic amino acid and possesses anti-obesity potential. However, the specific mechanisms by which gut microbiota might mediate beneficial effects of DL-norvaline have not been completely elucidated. In this study, DL-norvaline-mediated FMT upregulated the beneficial bacteria ( Clostridia_UCG_014 , Christensenellales , Bacilli , Ileibacterium , Dubosiella , Lactobacillus , Muribaculaceae , and Bacteroidaceae ) and downregulated the harmful bacteria ( Tuzzerella and Marinifilaceae ), further intestinal inflammation, oxidative stress, and intestinal barrier were alleviated as well as short chain fatty acids levels were increased, thus alleviating glucose and insulin metabolism, improving biochemical indexes and energy metabolism and decreasing body weight gain and tissue weight. However, heat-inactivated FMT did not demonstrate any of those improvements in obese mice. Notably, both DL-norvaline-mediated FMT and heat-inactivated FMT increased Bacteroidaceae and Muribaculaceae , this being a signature of alterations to the gut microbiota marker caused by DL-norvaline. Therefore, the beneficial effects of DL-norvaline were transmissible via FMT. This study highlighted the pivotal involvement of the gut microbiota in the development of obesity and provided a novel insight into the underlying mechanisms of FMT, thereby potentially enhancing the efficacy and refinement of FMT utilization.
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