Serum metabolome associated with severity of acute traumatic brain injury

CENTER-TBI Participants and Investigators

doi:10.1038/s41467-022-30227-5

Serum metabolome associated with severity of acute traumatic brain injury

CENTER-TBI Participants and Investigators

Örebro University
University of Turku and Turku University Hospital
Turku University Hospital
University of Pecs Medical School
University of Pécs
Erasmus University Medical Center
University of Florida College of Medicine
Antwerp University Hospital
Leiden University Medical Centre
University of Cambridge
Karolinska Institutet
Oslo University Hospital
University Hospital of North Norway
Medical University of Vienna
Hôpital Central
Raymond Poincaré Hospital
IRCCS San Raffaele Scientific Institute
Amalia Children's Hospital
University of Szeged
ARTTIC Innovation GmbH
Medical University Innsbruck
Karolinska Institutet at Karolinska University Hospital
NIHR Surgical Reconstruction and Microbiology Research Centre
AP-HP Sorbonne Université
Azienda Ospedaliera Città della Salute e della Scienza di Torino
Odense University Hospital
Monash University
Trnava University
Quesgen Systems Inc.
Umeå University
University Medical Center Hamburg-Eppendorf
Department of Clinical Neurosciences
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Hospital de Cruces
Imperial College London
Ospedale Niguarda Ca' Granda
Universit̀ Degli Studi di Milano-Bicocca
ASST di Monza
RWTH Aachen University
University of Bonn and University Hospital Bonn
Cambridge University Hospitals NHS Foundation Trust
Medical Research Council Cognition and Brain Sciences Unit
University Medical Center
Oxford University Hospitals NHS Trust
University Hospital
University of Manchester
Oxford Brookes University
AOU Maggiore della Carità
Leuven University Center for Metabolic Bone Diseases
Faculty of Medicine, University of Novi Sad
Charite Universitätsmedizin Berlin
CHR Citadelle
Rigshospitalet
Auckland University of Technology
Hadassah Hebrew University Medical Center
Fundación Instituto Valenciano de Neurorrehabilitación (FIVAN)
Jiao Tong University School of Medicine
Centre Hospitalier Universitaire de Liege
Pauls Stradins Clinical University Hospital
Hospital Universitario 12 de Octubre
Australian National University
All India Institute of Medical Sciences (AIIMS)
University of Sterling
University Medical Center Groningen
Sheffield Teaching Hospitals NHS Foundation Trust
Hope Hospital
University Hospital
University of Liège
University of Sheffield
University Witten-Herdecke
ICON
CHRU Roger Salengro
Rambam Medical Center
University Hospital Southampton NHS Foundation Trust
Southmead Hospital Bristol
University of California San Francisco
M. Bufalini Hospital
University Hospital Heidelberg
Walton Centre NHS Trust
Emergency County Hospital Timisoara
University of Helsinki
Massachusetts General Hospital
The Broad Institute of MIT and Harvard
University of Antwerp
CHU Grenoble 38043Grenoble
University Hospital Padua
Helsinki University Central Hospital
AP-HP
Vall d’Hebron University Hospital
Kaunas University of Technology
Rezekne Hospital
The University of Edinburgh Medical School
University of Cambridge
Biotechnology Centre of Oslo
International Neurotrauma Research Organisation (INRO)
Klinikum Ludwigsburg
University of Debrecen
Ernst-Moritz-Arndt Universität Greifswald
AUVA Trauma Hospital
Tweesteden Ziekenhuis Tilburg
Norwegian University of Science and Technology
St. Olavs Hospital
Johns Hopkins School of Medicine
Queen Elizabeth University Hospital, Glasgow
University of Milan
Lithuanian University of Health Sciences
University Medical Center Rotterdam
King's College London
Charité – Universitätsmedizin Berlin
Icometrix NV
School for Mental Health and Neuroscience
University of California at Los Angeles
VTT Technical Research Centre of Finland
Rady Faculty of Health Sciences

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

84 Scopus citations

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
State	Published - Dec 2022
Externally published	Yes

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10.1038/s41467-022-30227-5

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@article{43877261d1cf492285e81a1736417f14,

title = "Serum metabolome associated with severity of acute traumatic brain injury",

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 = "\{CENTER-TBI Participants and Investigators\} and 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 Simona Cavallo and Daniel Rueckert",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41467-022-30227-5",

language = "English",

volume = "13",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

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TY - JOUR

T1 - Serum metabolome associated with severity of acute traumatic brain injury

AU - CENTER-TBI Participants and Investigators

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 - Rueckert, 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.

UR - https://www.scopus.com/pages/publications/85130005214

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 -

Serum metabolome associated with severity of acute traumatic brain injury

Abstract

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