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 and Matej Orešič ()
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Ilias Thomas: Örebro University
Alex M. Dickens: University of Turku and Åbo Akademi University
Jussi P. Posti: Turku University Hospital and University of Turku
Endre Czeiter: University of Pécs
Daniel Duberg: Örebro University
Tim Sinioja: Örebro University
Matilda Kråkström: University of Turku and Åbo Akademi University
Isabel R. A. Retel Helmrich: Erasmus MC-University Medical Center
Kevin K. W. Wang: McKnight Brin Institute of the University of Florida
Andrew I. R. Maas: Antwerp University Hospital and University of Antwerp
Ewout W. Steyerberg: Erasmus MC-University Medical Center
David K. Menon: University of Cambridge, Addenbrooke’s Hospital
Olli Tenovuo: Turku University Hospital and University of Turku
Tuulia Hyötyläinen: Örebro University
András Büki: Örebro University
Matej Orešič: Örebro University

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41467-022-30227-5

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