Natto has long been considered as a medical-food dual-use product with a hypolipidemic effect. Our study showed that natto was effective in reducing the levels of total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), and increasing the level of high-density lipoprotein cholesterol (HDL-C) in the serum of hyperlipidemic mice. Metabolism analysis showed that natto could improve the levels of amino acid metabolites, reduce the contents of acylcarnitines, and reverse the levels of purine alkaloids, mainly involving the tricarboxylic acid (TCA) cycle and metabolism of amino acids. Moreover, natto increased beneficial gut microbiota (e.g., Lactobacillus, Faecalibaculum and Oscillibacter) and reduced pathogenic gut microbiota (e.g., Alistipes and Prevotellaceae-UCG-003). In conclusion, our findings suggest that natto-mediated changes in the gut microbiota and its related metabolites can support the prevention of high-fat diet (HFD)-induced hyperlipidemia, laying the theoretical foundation for the continued development of natto as...

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