Serum metabolome associated with severity of acute traumatic brain injury

Ilias Thomas, Alex M. Dickens, the CENTER-TBI Participants and Investigators, 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*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Article number2545
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - 10 May 2022

Bibliographical note

Acknowledgements
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).

Funding
Open access funding provided by Örebro University.

Publisher Copyright:
© 2022, The Author(s).

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