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The emerging field of immunometabolism has established that the metabolic pathways governing immune cell function—glycolysis, oxidative phosphorylation, fatty acid oxidation, and amino acid metabolism—are fundamental determinants of immune responses in health and disease. This review synthesizes current evidence on how dietary inputs serve as primary environmental modulators of this immunometabolism programming. We detail the mechanisms by which macronutrients (carbohydrates, lipids, proteins), micronutrients, and specific dietary patterns (e.g., Western, Mediterranean, ketogenic) engage key nutrient-sensing pathways (mechanistic target of rapamycin mTOR, AMP-activated protein kinase AMPK, hypoxia-inducible factor-1α HIF-1α, peroxisome proliferator-activated receptor PPARs) to rewire immune cell metabolism and influence functional phenotypes. A central role is afforded to the gut microbiota as a critical intermediary, translating diet into immunoregulatory signals, such as short-chain fatty acids. We further explore how obesogenic diets disrupt this network to fuel chronic low-grade inflammation (metaflammation), driving the pathophysiology of common metabolic diseases, including obesity, type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and atherosclerosis. Finally, we evaluate therapeutic nutritional strategies—from nutraceuticals and probiotics to the promise of precision nutrition—designed to recalibrate immunometabolism. This review underscores that diet is a powerful, modifiable lever of immunity, positioning targeted nutritional intervention as a pivotal strategy for preventing and managing metabolic disease.
Kousar et al. (Thu,) studied this question.