Urinary metabolomic signatures as indicators of injury severity following traumatic brain injury: A pilot study

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.

Identification of Serum Metabolites as Prognostic Biomarkers Following Spinal Cord Injury: A Pilot Study

“…Previous research from our group revealed potential urinary metabolomics biomarkers for SCI and traumatic brain injury [ 16 , 17 , 18 ]. While more metabolites are detectible in urine through nuclear magnetic resonance (NMR) spectroscopy, it is advantageous to investigate similarities and differences to blood-based biomarkers.…”

Non-invasive fluid biomarkers in the diagnosis of mild traumatic brain injury (mTBI): a systematic review

“…Additionally, this study demonstrated that there was a positive correlation between urinary 2-hydroxyisobutyrate concentrations and mTBI recovery as well as urinary lactose concentration and number of symptoms 28. Bykowski et al 31 reported a negative correlation between initial GCS taken within 7 days of TBI and three urinary metabolites (homovanillate, L-methionine and thymine) such that these urinary metabolites increased with lower GCS (ie, worse head injury).…”

“…However, 82.8% of studies included paediatric subjects. Eight studies specifically examined adult subjects17 22 23 29–33; 41.4% of studies specifically assessed youth, collegiate or professional sport populations.…”

“…Additional salivary biomarkers with reported diagnostic and disease monitoring value included BDNF and sEVs containing CDC2, capthepsin D and CSNK1A1 proteins 29 37. Urinary metabolic changes reported to have diagnostic value within the first week of injury included an upregulation of IGFBP5 and a downregulation of homovanillate, L-methionine and thymine 28 31 36. None of these non-RNA-based biomarkers have been further validated in follow-up studies.…”

Small molecule metabolites: discovery of biomarkers and therapeutic targets

“… 477 In a quantitative profiling study that focused on urinary metabolic signatures including homovanillate, L-methionine, and thymine as indicators of traumatic brain injury. 478 Concerning metabolic signatures of tumor growth stage, such as colorectal cancer, sporadic colorectal adenoma, and the potential metabolites such as D-mannose, sarcosine, 4,5-trimethoxybenzoic acid are found by serum metabolic screening. 479 By metabolic features of PCa analyses, Yu et al discovered a series of altered metabolites that were related to TCA, glycine cleavage system, fatty acid metabolism.…”