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; CENTER-TBI Participants and Investigators; Martin Fabricius; Daniel Kondziella

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, CENTER-TBI Participants and Investigators, Martin Fabricius (Member of study group), Daniel Kondziella (Member of study group)

^*Corresponding author for this work

10 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
ISSN	2041-1722
DOIs	https://doi.org/10.1038/s41467-022-30227-5
Publication status	Published - Dec 2022

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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., ... Kondziella, D. (2022). Serum metabolome associated with severity of acute traumatic brain injury. Nature Communications, 13(1), [2545]. https://doi.org/10.1038/s41467-022-30227-5

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, CENTER-TBI Participants and Investigators, Fabricius, M & Kondziella, D 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

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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.",

author = "Ilias Thomas and Dickens, {Alex M.} and Posti, {Jussi P.} and Endre Czeiter and Daniel Duberg and Tim Sinioja and Matilda Kr{\aa}kstr{\"o}m and {Retel Helmrich}, {Isabel R.A.} and Wang, {Kevin K.W.} and Maas, {Andrew I.R.} and Steyerberg, {Ewout W.} and Menon, {David K.} and Olli Tenovuo and Tuulia Hy{\"o}tyl{\"a}inen and Andr{\'a}s B{\"u}ki and Matej Ore{\v s}i{\v c} and Cecilia {\AA}kerlund and Krisztina Amrein and Nada Andelic and Lasse Andreassen and Audny Anke and Anna Antoni and G{\'e}rard Audibert and Philippe Azouvi and Azzolini, {Maria Luisa} and Ronald Bartels and P{\'a}l Barz{\'o} and Romuald Beauvais and Ronny Beer and Bellander, {Bo Michael} and Antonio Belli and Habib Benali and Maurizio Berardino and Luigi Beretta and Morten Blaabjerg and Peter Bragge and Alexandra Brazinova and Vibeke Brinck and Joanne Brooker and Camilla Brorsson and Monika Bullinger and Manuel Cabeleira and Alessio Caccioppola and Emiliana Calappi and Calvi, {Maria Rosa} and Peter Cameron and Lozano, {Guillermo Carbayo} and Marco Carbonara and {CENTER-TBI Participants and Investigators} and Martin Fabricius and Daniel Kondziella",

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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 - CENTER-TBI Participants and Investigators

A2 - Fabricius, Martin

A2 - Kondziella, Daniel

PY - 2022/12

Y1 - 2022/12

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.

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DO - 10.1038/s41467-022-30227-5

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VL - 13

JO - Nature Communications

JF - Nature Communications

SN - 2041-1722

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ER -

Serum metabolome associated with severity of acute traumatic brain injury

Abstract

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