Integrated Multi-omics Analysis Identifies Molecular Signatures of Regular Physical Activity in Human Peripheral Blood

Abstract

Regular physical activity is well established to protect against metabolic disorders and bolster immunity; yet, the underlying molecular and cellular mechanisms remain incompletely understood. Here, leveraging the Chinese Immune Multi-omics Atlas (CIMA), we integrated plasma metabolomics and lipidomics with single-cell transcriptomic and chromatin accessibility profiles (scRNA-seq and scATAC-seq) to decode the systemic impact of physical activity on human immunity and metabolism. Our data reveal that regular physical activity is linked to a coordinated metabolic signature marked by enhanced fatty acid oxidation and antioxidant defense. In circulating immune cells, it reprograms myeloid chromatin accessibility, activating antigen-presentation pathways while dampening inflammatory programs. Concurrently, effector functional programs in T cells and natural killer cells show extensive enhancement. Moreover, cellular communication analysis highlights a coordinated reinforcement of antigen presentation and chemotaxis signaling. Together, these findings elucidate molecular mechanisms underlying exercise-induced health benefits and offer a theoretical basis for enhancing public health and preventing chronic diseases.