Abstract
BACKGROUND/OBJECTIVES: Metabolomics has emerged as a powerful systems-biology tool for deciphering dynamic metabolic alterations occurring during infectious diseases and following vaccination. While genomics and proteomics provide extensive molecular and regulatory information, metabolomics uniquely reflects the biochemical phenotype associated with infection, immune activation, and immunometabolic reprogramming. The objective of this review is to provide an integrated analysis of metabolomics applications across both neglected tropical diseases (NTDs) and non-NTD pathogens, highlighting its dual role in biomarker discovery and vaccine response evaluation. METHODS: A comprehensive literature-based synthesis was conducted to examine metabolomic studies in infectious diseases and vaccinology. Metabolic perturbations associated with specific pathogens, as well as vaccine-induced metabolic changes and correlates of immune responses, were systematically analyzed and compared across NTD and non-NTD contexts. RESULTS: Distinct pathogen- and vaccine-associated metabolic signatures were identified, reflecting alterations in glycolysis, amino acid metabolism, lipid remodeling, and immunoregulatory pathways. Comparative analysis revealed both shared and disease-specific metabolic biomarkers across NTDs and non-NTD infections. Importantly, vaccine-related metabolic correlates were shown to mirror immune activation states and, in some cases, predict immunogenicity and response durability. CONCLUSIONS: This review bridges metabolomics research in infectious disease pathogenesis and vaccine immunology across the NTD and non-NTD spectrum. By integrating these domains, it introduces the concept of "metabolic immuno-signatures" as predictive and translational tools for evaluating vaccine efficacy and immune response outcomes.