GPCS Stratification of Exercise-Induced Gut Microbiota and Metabolome Remodeling in IBS: An Exploratory Multi-Omics Study

Background/Objectives: Exercise is increasingly recognized as a modulator of host–microbiome interactions, yet its role in irritable bowel syndrome (IBS) remains poorly characterized. Methods: In this prospective, single-arm, before-and-after interventional study, we used an integrated multi-omics approach based on metataxonomics and metabolomics to assess the effects of a structured 12-week moderate aerobic exercise program in 80 patients with mild-to-moderate IBS, stratified by Global Physical Capacity Score (GPCS). Biochemical and inflammatory markers have been gathered. Results: Exercise did not alter overall microbial diversity but selectively enriched short-chain fatty acid (SCFA)-producing taxa and remodeled the volatile organic compound (VOC) profile toward a more efficient metabolic state. Notably, conventional biochemical and inflammatory markers failed to distinguish response subgroups, whereas GPCS stratification revealed distinct microbial and metabolomic trajectories. Individuals with higher baseline physical capacity had higher acetate levels and lower levels of VOCs associated with dysbiosis and oxidative stress. Conclusions: Our results suggest that baseline physical capacity is a primary determinant of the microbiome’s responsiveness to exercise, challenging the reliance on static biochemical profiling. Despite the lack of a control group and the exploratory nature of some metabolomic signals, this study provides a framework for precision exercise interventions in IBS. Our work identifies GPCS as a clinically relevant stratification tool. The full trial protocol is registered on ClinicalTrials.gov under the identifier NCT05453084.