Title : Immunonutritional reprogramming: Harnessing cellular metabolism to modulate immune plasticity in chronic and critical illness
Abstract:
This presentation offers an updated bibliographic review on immunonutritional reprogramming, an emerging approach that integrates immunology, cellular metabolism, and clinical nutrition to influence immune functionality in patients with chronic and critical illness. The central concept is that specific nutrients — including arginine, omega-3 fatty acids, glutamine, and butyrate — can actively shape immune cell behavior by modulating metabolic pathways such as mTOR, AMPK, HIF-1α, and PPARγ.
Dietary supplementation with immunomodulatory nutrients has shown to enhance lymphocyte proliferation, reduce postoperative infections, and shorten hospital stays in patients undergoing major surgery. Clinical trials demonstrate that immunonutrition strategies can decrease complication rates and improve clinical outcomes, especially in malnourished or oncologic populations. However, certain nutrients like arginine may have adverse effects in septic patients due to increased nitric oxide synthesis and its interaction with arginase activity. At the molecular level, butyrate—produced by gut microbiota during fiber fermentation—acts as a histone deacetylase inhibitor and ligand for GPR109A and FFAR receptors. It promotes regulatory T cell (Treg) differentiation, suppresses pro-inflammatory cytokine production, and enhances intestinal epithelial integrity. This highlights the role of the gut-immune-metabolite axis as a critical hub for systemic immune modulation.
From an immunometabolic perspective, macrophage and T cell fate decisions are deeply tied to metabolic state. Pro-inflammatory macrophages (M1) rely on aerobic glycolysis, resulting in succinate accumulation, ROS production, and HIF-1α stabilization. In contrast, anti-inflammatory macrophages (M2) and Tregs depend on sustained oxidative phosphorylation and lipid β-oxidation for proper function. Recent studies also indicate that diets rich in fiber and omega-3 fatty acids can remodel immune cell metabolism in adipose tissue, reducing inflammatory markers and improving insulin sensitivity in obesity models. These findings support the view that dietary inputs can reprogram innate and adaptive immunity via metabolic rewiring.
Moreover, the concept of trained immunity and innate memory is now linked to nutritional modulation. Nutrients and metabolites can induce epigenetic reprogramming — such as histone acetylation, lactylation, and methylation — which shape long-term immune responses beyond antigen specificity. This opens the door to using targeted nutrition to restore immune homeostasis in post-critical illness, cancer, and chronic inflammation. The emerging field of immunonutrigenomics integrates genomic, epigenetic, and metabolic data to stratify patients for personalized dietary interventions. Advanced platforms using metabolomics and immune phenotyping are being developed to guide individualized nutrition plans with immune-regulatory objectives.
In summary, immunonutritional reprogramming represents a paradigm shift, moving beyond micronutrient supplementation toward precision-based interventions aimed at cellular and functional immune recovery. This presentation synthesizes high-level evidence and translational perspectives to position nutrition as a therapeutic ally in immune modulation for complex clinical settings.
