Macrophage metabolic reprogramming by melanoidin-like carbohydrate-containing macromolecules from Shanxi aged vinegar: A global metabolomics analysis

Abstract Carbohydrate-containing macromolecules (CCM), particularly Maillard-modified derivatives with inherent bioactivities, are widely distributed in thermally processed foods. Melanoidin-like carbohydrate-containing macromolecules (MCCM) derived from Shanxi aged vinegar (MCCM-SAV) have been previously shown to exert immunoenhancing effects on macrophages; however, their role in regulating macrophage metabolic reprogramming remains insufficiently elucidated. In this study, non-targeted metabolomics was employed to systematically investigate global metabolic alterations in macrophages induced by MCCM-SAV. Results identified 128 significantly altered intracellular metabolites and 30 perturbed metabolic pathways, among which seven core pathways and nine key differential metabolites were prioritised. Notably, these metabolic shifts were corroborated by enhanced glucose uptake and lactic acid production, hallmark events associated with aerobic glycolysis activation. Collectively, this work establishes a comprehensive metabolic landscape of MCCM-SAV-mediated macrophage reprogramming, unravelling the underlying metabolic adaptations that may mechanistically support their immunomodulatory functions. These findings not only reveal the immunometabolic regulatory mechanism of food-derived Maillard-related bioactive macromolecules, but also provide a theoretical basis and scientific support for the development of novel immune-enhancing functional foods and nutritional supplements. By linking macrophage metabolic reprogramming to the health-promoting effects of food-borne bioactive components, this study highlights the nutritional value and application potential of MCCM-SAV in food science and human nutrition.