Multiomics Study Identifies Distinct Metabolic and Immune Signatures in Regular Exercisers

On September 18, 2026, investigators from BGI-Research and partner institutes published a comprehensive multiomics atlas demonstrating that regular exercise fundamentally rewires the human immune system at the epigenetic level.[1][3][5]

The study, detailed in the journal Science Advances, analyzed blood samples from 86 healthy young adults to map the precise molecular and cellular differences between active and sedentary lifestyles.[1][2]

Drawing from the Chinese Immune Multi-Omics Atlas (CIMA), researchers compared 40 individuals who met World Health Organization physical activity guidelines—accumulating at least 150 minutes of moderate or 75 minutes of vigorous exercise weekly—against 46 participants who reported no purposeful exercise.[2][3]

To capture a high-resolution picture of exercise adaptation, the team ran four separate technologies on the participants' blood: targeted metabolomics on 321 small molecules, lipidomics on 718 lipid species, single-cell RNA sequencing on 1.3 million immune cells, and single-cell chromatin accessibility sequencing on another 644,000 cells.[3]

The resulting metabolic profile aligned with physiological expectations for active individuals. The exercising cohort showed elevated levels of fat-burning intermediates, including acylcarnitines, ketone bodies, and acetic acid, signaling a body that routinely pulls fat into mitochondria for oxidation.[2][3]

Regular exercisers also exhibited significantly lower fasting blood glucose and triglyceride levels, alongside higher concentrations of high-density lipoprotein (HDL) cholesterol and antioxidant-related metabolites like 3-hydroxyanthranilic acid.[2]

Beyond these metabolic shifts, the study uncovered a striking epigenetic reprogramming within the circulating immune cells of the active group.[1][3][4]

Antigen-presenting cells, specifically classical monocytes and B cells, had physically opened the DNA around their antigen presentation genes. This structural change in chromatin accessibility indicates a state of primed alertness, allowing the immune system to respond more rapidly to pathogens.[1][3]

Similarly, CD8+ cytotoxic T cells and mature natural killer (NK) cells in the exercising group sat pre-loaded with effector machinery, showing epigenetic preactivation of their defensive functions.[1][3]

Intercellular communication models further predicted stronger major histocompatibility complex (MHC-I/II) signaling between these immune cells, coupled with damped-down inflammatory signaling through pathways like interleukin-6 (IL-6) and resistin.[1][2][3]

Investigators from BGI-Research noted that the findings demonstrate how the benefits of physical activity "extend far beyond caloric expenditure, encompassing metabolic reprogramming and multidimensional, coordinated epigenetic alterations in the immune system."[5]

While the study relied on a relatively small sample of non-obese adults aged 20 to 40, the findings provide the field with a concrete set of chromatin-level biomarkers to measure how the human body actually adapts to regular physical activity.[2][3]