Urine metabolomics reveals key pathways supporting neuronal regeneration and consciousness recovery in disorders of consciousness

Disorders of consciousness (DoC) are debilitating conditions resulting from severe brain injury, requiring not only structural preservation but also active neuronal regeneration for recovery. These regenerative processes are metabolically demanding and can be tracked through systemic metabolic changes. Urine metabolomics provides a non-invasive approach to identifying metabolic signatures linked to neural recovery.

This study aimed to determine whether urinary metabolic profiles reflect clinical classifications in DoC and identify pathways associated with neuronal regeneration and consciousness recovery. Urine samples from 37 DoC patients were analyzed using untargeted metabolomics. Patients were categorized by etiology, diagnosis, and prognosis.

Statistical and pathway enrichment analyses identified group-specific metabolic alterations. Urine metabolomics revealed distinct metabolic patterns across etiologies, consciousness levels, and prognoses. Pyrimidine, nitrogen, and arginine metabolism were elevated in traumatic brain injury (TBI) patients, potentially reflecting sustained oxidative stress and regeneration.

Patients with improved outcomes exhibited alterations in amino acid and tryptophan metabolism, suggesting enhanced neuroplasticity. Several metabolites showed strong predictive value for recovery. Urinary metabolic profiles reflect both clinical classification and underlying regenerative activity in DoC.

TBI patients may benefit from chronic oxidative stress that influences neural remodeling, while patients with higher consciousness levels exhibit ascorbate-related dopaminergic metabolic patterns that may facilitate a positive feedback loop for recovery. Urine metabolomics is a practical, non-invasive approach to identify biomarkers and pathways associated with neuronal regeneration and consciousness recovery in DoC. Beyond prognostic utility, these metabolic signatures provide mechanistic clues to the metabolic–neurorepair processes that may enable large-scale network reactivation and the return of consciousness, warranting longitudinal validation and targeted pathway testing.

DA–Orthogonal partial least squares discriminant analysis MS–Ultra–performance liquid chromatography–mass spectrometry The authors thank all participants in this study. We would like to acknowledge the assistance of AI tools, specifically ChatGPT, for providing language editing and improving the clarity and readability of the manuscript text. After using this tool, the authors carefully reviewed and revised the content as needed and take full responsibility for the content of the published article.