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; Cecilia Åkerlund; Krisztina Amrein; Nada Andelic; Lasse Andreassen; Audny 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

doi:10.1038/s41467-022-30227-5

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^*, 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

^*Corresponding author for this work

Research output: Contribution to journal › Article › Scientific › peer-review

54 Citations (Scopus)

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.

Original language	English
Article number	2545
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-30227-5
Publication status	Published - 10 May 2022
MoE publication type	A1 Journal article-refereed

Funding

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.

Keywords

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

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Thomas, I., Dickens, A. M., Posti, J. P., Czeiter, E., Duberg, D., Sinioja, T., Kråkström, M., Retel Helmrich, I. R. A., Wang, K. K. W., Maas, A. I. R., Steyerberg, E. W., Menon, D. K., Tenovuo, O., Hyötyläinen, T., Büki, A., Orešič, M., Åkerlund, C., Amrein, K., Andelic, N., ... CENTER-TBI investigators and participants (2022). Serum metabolome associated with severity of acute traumatic brain injury. Nature Communications, 13(1), Article 2545. https://doi.org/10.1038/s41467-022-30227-5

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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.",

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Thomas, I, Dickens, AM, Posti, JP, Czeiter, E, Duberg, D, Sinioja, T, Kråkström, M, Retel Helmrich, IRA, Wang, KKW, Maas, AIR, Steyerberg, EW, Menon, DK, Tenovuo, O, Hyötyläinen, T, Büki, A, Orešič, M, Åkerlund, C, Amrein, K, Andelic, N, Andreassen, L, Anke, A, Antoni, A, Audibert, G, Azouvi, P, Azzolini, ML, Bartels, R, Barzó, P, Beauvais, R, Beer, R, Bellander, BM, Belli, A, Benali, H, Berardino, M, Beretta, L, Blaabjerg, M, Bragge, P, Brazinova, A, Brinck, V, Brooker, J, Brorsson, C, Bullinger, M, Cabeleira, M, Caccioppola, A, Calappi, E, Calvi, MR, Cameron, P, Lozano, GC, Carbonara, M, Cavallo, S, Ylén, P & CENTER-TBI investigators and participants 2022, 'Serum metabolome associated with severity of acute traumatic brain injury', Nature Communications, vol. 13, no. 1, 2545. https://doi.org/10.1038/s41467-022-30227-5

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

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

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U2 - 10.1038/s41467-022-30227-5

DO - 10.1038/s41467-022-30227-5

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AN - SCOPUS:85130005214

SN - 2041-1723

VL - 13

JO - Nature Communications

JF - Nature Communications

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M1 - 2545

ER -

Serum metabolome associated with severity of acute traumatic brain injury

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