Immunometabolomics Applied to Physical Exercise: Accomplishments and New Directions for Health Improvement

Abstract

Immunometabolomics is a multidisciplinary field that explores how metabolic pathways regulate immune cell function, using metabolomics—the large-scale analysis of small molecules (metabolites)—to map these interactions in health and disease. Emerging evidence highlights that metabolic shifts are not merely by-products but key drivers of exercise-induced immune adaptations, with significant implications for performance, recovery, and disease prevention. This narrative review summarizes the latest findings on how exercise shapes immune responses through metabolic pathways. We discuss how key metabolites, such as succinate, itaconate, lactate, short-chain fatty acids, and kynurenine, act as molecular links between energy metabolism and immune regulation during and after exercise. We also investigate the effects of physical exercise on immunometabolic profiles within distinct tissues, elucidating their roles in promoting either proinflammatory or anti-inflammatory adaptations. Methodological advances in metabolomics and multi-omics are also addressed. Our review highlights robust evidence from human trials that physical exercise reprograms immunometabolic pathways in a time-, tissue-, and modality-specific manner, supporting its role in both health maintenance and clinical interventions.