Inter-Individual Variability in Exercise-Induced Metabolic Responses Revealed by Breath and Blood High-Resolution Mass Spectrometry-Based Metabolomics

Interindividual heterogeneity represents a major challenge for precise monitoring of exercise-induced physiological responses. In this study, a metabolomics-based framework was established to investigate individual variability in metabolic adaptations to exercise and its association with baseline breath profiles. Breath and blood samples were collected before and after a two-week training intervention. Blood metabolomic alterations were first evaluated through differential analysis to identify training-responsive features after training. The magnitude of change for each feature was then calculated to quantify individual metabolic responses. Correlation analysis was subsequently performed to assess the relationships between baseline breath metabolite intensities and the magnitude of blood metabolite changes. Hierarchical clustering and heatmap analysis were used to characterize global association patterns. The results showed that a subset of blood metabolites exhibited altered responses after training, potentially associated with energy metabolism, oxidative stress, and inflammatory processes. Importantly, the magnitude of these changes displayed pronounced interindividual heterogeneity under the same training conditions. Furthermore, multiple baseline breath metabolites were found to be significantly associated with the magnitude of blood metabolite changes, revealing structured relationships between breath profiles and systemic metabolic responses. In conclusion, exercise-induced metabolic alterations in blood are characterized by substantial individual variability, and baseline breath metabolome is associated with the magnitude of these changes, providing a methodological basis for further studies on noninvasive characterization of individual metabolic responses.