Precision Rehabilitation in Spinal Cord Injury: A Systematic Review of Omics Applications for Intervention Monitoring in Spinal Cord Injury

<h4>Objective</h4>To systematically evaluate the application and utility of omics technologies, high-throughput methods measuring the complete or targeted set of molecules inside a biological system at a certain timepoint, in monitoring and optimizing rehabilitation interventions in traumatic spinal cord injury.<h4>Data sources</h4>Embase, Medline/Ovid, and Web of Science were searched from inception to November 27, 2024.<h4>Study selection</h4>Eligible studies included adults (≥18 years) with spinal cord injury undergoing rehabilitation interventions assessed using omics technologies (genomics, epigenomics, transcriptomics, proteomics, metabolomics, or metagenomics).<h4>Data extraction</h4>Following PRISMA guidelines, independent screening, data extraction, and risk of bias (RoB) assessment (National Institutes of Health Quality Assessment Tools) were performed by 2 investigators. Based on RoB assessment, studies were classified from level 1 (most reliable) to level 4 (least reliable).<h4>Data synthesis</h4>Twenty-three trials were included: 8 randomized controlled trials, 5 non-randomized controlled trials, and 10 pre-post trials. Twenty-two studies (96%) exhibit a moderate RoB due to small sample size and heterogeneity. Omics technologies were primarily applied to exercise and electrical muscle stimulation interventions (65%), followed by hormonal and cellular therapies (22%), and diet (13%). Transcriptomic analyses revealed consistent molecular adaptations, including increased mitochondrial biogenesis (proliferator-activated receptor gamma coactivator 1-alpha) and reduced muscle atrophy gene expression (myostatin), correlating with enhanced insulin sensitivity and improved aerobic capacity. Metagenomics consistently identified microbiome shifts, such as decreased inflammatory taxa and increased beneficial taxa, associated with improved metabolic profiles and bowel function. Proteomics and metabolomics highlighted systemic changes related to neurorecovery, immune modulation, and sperm motility, linking molecular signatures directly to clinical outcomes.<h4>Conclusions</h4>Omics technologies enable early identification of molecular alterations. However, given small sample sizes and heterogeneity of the current studies, these findings should be interpreted with caution. Gradual integration of omics, particularly epigenomics which may capture long-term, injury-related changes holds promise for developing personalized rehabilitation protocols and monitoring clinical progression in spinal cord injury.