Serum metabolome associated with severity of acute traumatic brain injury

Ilias Thomas, Alex M. Dickens, Jussi P. Posti, Endre Czeiter, Daniel Duberg, Tim Sinioja, Matilda Kråkström, Isabel R.A. Retel Helmrich, Kevin K.W. Wang, Andrew I.R. Maas, Ewout W. Steyerberg, David K. Menon, Olli Tenovuo, Tuulia Hyötyläinen, András Büki, Matej Orešič (Corresponding Author), Cecilia Åkerlund, Krisztina Amrein, Nada Andelic, Lasse AndreassenAudny Anke, Anna Antoni, Gérard Audibert, Philippe Azouvi, Maria Luisa Azzolini, Ronald Bartels, Pál Barzó, Romuald Beauvais, Ronny Beer, Bo Michael Bellander, Antonio Belli, Habib Benali, Maurizio Berardino, Luigi Beretta, Morten Blaabjerg, Peter Bragge, Alexandra Brazinova, Vibeke Brinck, Joanne Brooker, Camilla Brorsson, Monika Bullinger, Manuel Cabeleira, Alessio Caccioppola, Emiliana Calappi, Maria Rosa Calvi, Peter Cameron, Guillermo Carbayo Lozano, Marco Carbonara, Simona Cavallo, Peter Ylén, CENTER-TBI investigators and participants

Research output: Contribution to journalArticleScientificpeer-review


Complex metabolic disruption is a crucial aspect of the pathophysiology of traumatic brain injury (TBI). Associations between this and systemic metabolism and their potential prognostic value are poorly understood. Here, we aimed to describe the serum metabolome (including lipidome) associated with acute TBI within 24 h post-injury, and its relationship to severity of injury and patient outcome. We performed a comprehensive metabolomics study in a cohort of 716 patients with TBI and non-TBI reference patients (orthopedic, internal medicine, and other neurological patients) from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) cohort. We identified panels of metabolites specifically associated with TBI severity and patient outcomes. Choline phospholipids (lysophosphatidylcholines, ether phosphatidylcholines and sphingomyelins) were inversely associated with TBI severity and were among the strongest predictors of TBI patient outcomes, which was further confirmed in a separate validation dataset of 558 patients. The observed metabolic patterns may reflect different pathophysiological mechanisms, including protective changes of systemic lipid metabolism aiming to maintain lipid homeostasis in the brain.

Original languageEnglish
Article number2545
JournalNature Communications
Issue number1
Publication statusPublished - 10 May 2022
MoE publication typeA1 Journal article-refereed


  • Brain Injuries
  • Brain Injuries, Traumatic
  • Cohort Studies
  • Humans
  • Metabolome
  • Metabolomics/methods


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