Abstract
BACKGROUND: Analysis of fluid metabolites has the potential to provide insight into the neuropathophysiology of injury in patients with traumatic brain injury (TBI). OBJECTIVE: Using a (1)H nuclear magnetic resonance (NMR)-based quantitative metabolic profiling approach, this study determined (1) if urinary metabolites change during recovery in patients with mild to severe TBI; (2) whether changes in urinary metabolites correlate to injury severity; (3) whether biological pathway analysis reflects mechanisms that mediate neural damage/repair throughout TBI recovery. METHODS: Urine samples were collected within 7 days and at 6-months post-injury in male participants (n = 8) with mild-severe TBI. Samples were analyzed with NMR-based quantitative spectroscopy for metabolomic profiles and analyzed with multivariate statistical and machine learning-based analyses. RESULTS: Lower levels of homovanillate (R = -0.74, p ≤ 0.001), L-methionine (R = -0.78, p < 0.001), and thymine (R = -0.85, p < 0.001) negatively correlated to injury severity. Pathway analysis revealed purine metabolism to be a primary pathway (p < 0.01) impacted by TBI. CONCLUSION: This study provides pilot data to support the use of urinary metabolites in clinical practice to better interpret biochemical changes underlying TBI severity and recovery. The discovery of urinary metabolites as biomarkers may assist in objective and rapid identification of TBI severity and prognosis. Thus, (1)H NMR metabolomics has the potential to facilitate the adaptation of treatment programs that are personalized to the patient's needs.