Immunonutrients as modulators of inflammation, barrier integrity, and immune regulation: Toward precision nutrition

Immunonutrient has emerged as a critical discipline integrating immunology, nutrition, and precision medicine. Key immunonutrients—including omega-3 fatty acids, vitamins D, C, and E, zinc, selenium, glutamine, arginine, polyphenols, and probiotics—modulate innate and adaptive immunity through mechanisms involving cytokine regulation, barrier function enhancement, immune cell differentiation, and redox balance. Multi-omics technologies have revealed substantial inter-individual variability in nutrient-immune interactions, driven by genetic polymorphisms, metabolic phenotypes, and microbiome composition. Clinical evidence demonstrates that immunonutrients reduce inflammatory markers, lower infection rates, and improve outcomes in surgical, critical care, autoimmune, and infectious disease contexts. Maternal and pediatric immunonutrient influences lifelong immune competence through developmental programming. However, challenges persist in defining optimal dosages, evaluating nutrient synergies, and translating precision nutrition into clinical practice. This review highlights the integration of genomics, metabolomics, and artificial intelligence to enable individualized immunonutrient interventions. By moving beyond population-based recommendations, precision immunonutrient represents a cornerstone of personalized healthcare with potential to optimize immune resilience across diverse clinical populations. This review synthesizes current evidence on the molecular mechanisms by which key immunonutrients modulate immune responses and explores how precision nutrition frameworks can translate inter-individual variability into personalized therapeutic strategies. • Provides an up-to-date synthesis of the role of immunonutrients in modulating inflammation, barrier integrity, and immune regulation. • Discusses both innate and adaptive immune responses influenced by omega-3 fatty acids, vitamins, trace elements, amino acids, polyphenols, and probiotics. • Emphasizes the transition of immunonutrition into the framework of precision nutrition, considering genetic, metabolic, microbial, and lifestyle determinants. • Reviews clinical evidence supporting immunonutrient use in infectious diseases, autoimmune disorders, perioperative recovery, and maternal–early life health. • Explores future directions, highlighting omics technologies and machine learning as tools for individualized nutritional interventions.