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Human Serum Metabolites Associate With Severity and Patient Outcomes in Traumatic Brain Injury

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  • Matej Orešič
  • Jussi P Posti
  • Maja Hermann Kamstrup-Nielsen
  • Riikka S K Takala
  • Hester F Lingsma
  • Ismo Mattila
  • Sirkku Jäntti
  • Ari J Katila
  • Keri L H Carpenter
  • Henna Ala-Seppälä
  • Anna Kyllönen
  • Henna-Riikka Maanpää
  • Jussi Tallus
  • Jonathan P Coles
  • Iiro Heino
  • Janek Frantzén
  • Peter J Hutchinson
  • David K Menon
  • Olli Tenovuo
  • Tuulia Hyotylainen
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Traumatic brain injury (TBI) is a major cause of death and disability worldwide, especially in children and young adults. TBI is an example of a medical condition where there are still major lacks in diagnostics and outcome prediction. Here we apply comprehensive metabolic profiling of serum samples from TBI patients and controls in two independent cohorts. The discovery study included 144 TBI patients, with the samples taken at the time of hospitalization. The patients were diagnosed as severe (sTBI; n=22), moderate (moTBI; n=14) or mild TBI (mTBI; n=108) according to Glasgow Coma Scale. The control group (n=28) comprised of acute orthopedic non-brain injuries. The validation study included sTBI (n=23), moTBI (n=7), mTBI (n=37) patients and controls (n=27). We show that two medium-chain fatty acids (decanoic and octanoic acids) and sugar derivatives including 2,3-bisphosphoglyceric acid are strongly associated with severity of TBI, and most of them are also detected at high concentrations in brain microdialysates of TBI patients. Based on metabolite concentrations from TBI patients at the time of hospitalization, an algorithm was developed that accurately predicted the patient outcomes (AUC=0.84 in validation cohort). Addition of the metabolites to the established clinical model (CRASH), comprising clinical and computed tomography data, significantly improved prediction of patient outcomes. The identified 'TBI metabotype' in serum, that may be indicative of disrupted blood-brain barrier, of protective physiological response and altered metabolism due to head trauma, offers a new avenue for the development of diagnostic and prognostic markers of broad spectrum of TBIs.

Original languageEnglish
JournalEBioMedicine
Volume12
Pages (from-to)118-126
Number of pages9
DOIs
Publication statusPublished - Oct 2016
Externally publishedYes

    Research areas

  • Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers, Brain Injuries, Traumatic, Female, Glasgow Coma Scale, Humans, Male, Metabolome, Metabolomics, Middle Aged, Patient Outcome Assessment, Prognosis, Prospective Studies, ROC Curve, Reproducibility of Results, Severity of Illness Index, Tomography, X-Ray Computed, Workflow, Young Adult, Journal Article, Multicenter Study

ID: 51480439