Resistance Training Complements Anti-TNF Therapy in DSS-Induced Colitis by Improving Skeletal Muscle Inflammatory and Mitochondrial Gene Signatures

Inflammatory bowel disease (IBD) is associated with skeletal muscle loss and mitochondrial dysfunction, which may compromise therapeutic responsiveness. We investigated whether progressive resistance training could improve muscle oxidative phosphorylation gene expression and enhance the efficacy of anti-TNF-α therapy (infliximab) in a dextran sulfate sodium (DSS)-induced colitis mouse model. Male C57BL/6 mice with subacute DSS-induced colitis were assigned to control, DSS, DSS + resistance training, DSS + anti-TNF-α, and DSS + resistance training + anti-TNF-α groups (n = 6 each). Resistance training consisted of 8 weeks of progressive ladder climbing; anti-TNF-α was administered at weeks 0, 2, and 6. Outcomes included body weight, disease activity, muscle function, histology, serum cytokines, muscle transcriptomics, and qPCR. DSS caused weight loss, functional decline, elevated proinflammatory cytokines, suppressed mitochondrial gene expression, and muscle inflammation. Resistance training or anti-TNF-α alone partially restored performance and mitochondrial gene expression while reducing inflammation. Their combination yielded superior effects (p < 0.01), normalizing histology. These findings suggest that resistance training may improve muscle metabolic status and attenuate systemic inflammation, thereby contributing to enhanced anti-TNF-α therapy outcomes in this preclinical model. Further studies are warranted to elucidate the underlying mechanisms and evaluate the translational potential.