TY - JOUR
T1 - Serum metabolome associated with severity of acute traumatic brain injury
AU - Thomas, Ilias
AU - Dickens, Alex M.
AU - Posti, Jussi P.
AU - Czeiter, Endre
AU - Duberg, Daniel
AU - Sinioja, Tim
AU - Kråkström, Matilda
AU - Retel Helmrich, Isabel R.A.
AU - Wang, Kevin K.W.
AU - Maas, Andrew I.R.
AU - Steyerberg, Ewout W.
AU - Menon, David K.
AU - Tenovuo, Olli
AU - Hyötyläinen, Tuulia
AU - Büki, András
AU - Orešič, Matej
AU - Åkerlund, Cecilia
AU - Amrein, Krisztina
AU - Andelic, Nada
AU - Andreassen, Lasse
AU - Anke, Audny
AU - Antoni, Anna
AU - Audibert, Gérard
AU - Azouvi, Philippe
AU - Azzolini, Maria Luisa
AU - Bartels, Ronald
AU - Barzó, Pál
AU - Beauvais, Romuald
AU - Beer, Ronny
AU - Bellander, Bo Michael
AU - Belli, Antonio
AU - Benali, Habib
AU - Berardino, Maurizio
AU - Beretta, Luigi
AU - Blaabjerg, Morten
AU - Bragge, Peter
AU - Brazinova, Alexandra
AU - Brinck, Vibeke
AU - Brooker, Joanne
AU - Brorsson, Camilla
AU - Bullinger, Monika
AU - Cabeleira, Manuel
AU - Caccioppola, Alessio
AU - Calappi, Emiliana
AU - Calvi, Maria Rosa
AU - Cameron, Peter
AU - Lozano, Guillermo Carbayo
AU - Carbonara, Marco
AU - Cavallo, Simona
AU - Ylén, Peter
AU - CENTER-TBI investigators and participants
N1 - Funding Information:
CENTER-TBI was supported by the European Union 7th Framework program (grant no. 602150), with additional project support from OneMind (US), the Hannelore Kohl Foundation (DE), NeuroTrauma Sciences (US), and Integra Neurosciences. The metabolomics study was supported by a grant from Swedish Research Council to M.O. (grant no. 2018-02629). The study was supported by funding from the Academy of Finland to J.P.P. (grant no. 17379), a grant from Government’s Special Financial Transfer tied to academic research in Health Sciences, Finland to J.P.P. (grant no. 11129) a grant from Maire Taponen Foundation to J.P.P. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors thank Daniel Duberg, Lisanna Sinisalu, and Vanja Stefanović for technical assistance in metabolomics analysis and to Dr. Aidan McGlinchey for assistance with language editing. The authors also thank Iftakher Hossain, Janek Frantzén, Mark van Gils, Peter J. Hutchinson, Ari J. Katila, Henna-Riikka Maanpää, Mehrbod Mohammadian, Virginia F. Newcombe, Jussi Tallus and Riikka S.K. Takala (The TBIcare study group).
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/5/10
Y1 - 2022/5/10
N2 - 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.
AB - 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.
KW - Brain Injuries
KW - Brain Injuries, Traumatic
KW - Cohort Studies
KW - Humans
KW - Metabolome
KW - Metabolomics/methods
UR - http://www.scopus.com/inward/record.url?scp=85130005214&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-30227-5
DO - 10.1038/s41467-022-30227-5
M3 - Article
C2 - 35538079
AN - SCOPUS:85130005214
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2545
ER -