Serum metabolome associated with severity of acute traumatic brain injury
Authors: Thomas Ilias , Dickens Alex M. , Posti Jussi P. , Czeiter Endre , Duberg Daniel , Sinioja Tim , Kråkström Matilda , Retel Helmrich Isabel R. A. , Wang Kevin K. W. , Maas Andrew I. R. , Steyerberg Ewout W. , Menon David K. , Tenovuo Olli , Hyötyläinen Tuulia , Büki András , Orešič Matej ,   CENTER-TBI Participants and Investigators, Åkerlund Cecilia , Amrein Krisztina , Andelic Nada , Andreassen Lasse , Anke Audny , Antoni Anna , Audibert Gérard , Azouvi Philippe , Azzolini Maria Luisa , Bartels Ronald , Barzó Pál , Beauvais Romuald , Beer Ronny , Bellander Bo-Michael , Belli Antonio , Benali Habib , Berardino Maurizio , Beretta Luigi , Blaabjerg Morten , Bragge Peter , Brazinova Alexandra , Brinck Vibeke , Brooker Joanne , Brorsson Camilla , Bullinger Monika , Cabeleira Manuel , Caccioppola Alessio , Calappi Emiliana , Calvi Maria Rosa , Cameron Peter , Lozano Guillermo Carbayo , Carbonara Marco , Cavallo Simona , Chevallard Giorgio , Chieregato Arturo , Citerio Giuseppe , Clusmann Hans , Coburn Mark , Coles Jonathan , Cooper Jamie D. , Correia Marta , Čović Amra , Curry Nicola , Czeiter Endre , Czosnyka Marek , Dahyot-Fizelier Claire , Dark Paul , Dawes Helen , De Keyser Véronique , Degos Vincent , Corte Francesco Della , den Boogert Hugo , Depreitere Bart , Đilvesi Đula , Dixit Abhishek , Donoghue Emma , Dreier Jens , Dulière Guy-Loup , Ercole Ari , Esser Patrick , Ezer Erzsébet , Fabricius Martin , Feigin Valery L. , Foks Kelly , Frisvold Shirin , Furmanov Alex , Gagliardo Pablo , Galanaud Damien , Gantner Dashiell , Gao Guoyi , George Pradeep , Ghuysen Alexandre , Giga Lelde , Glocker Ben , Golubovic Jagoš , Gomez Pedro A. , Gratz Johannes , Gravesteijn Benjamin , Grossi Francesca , Gruen Russell L. , Gupta Deepak , Haagsma Juanita A. , Haitsma Iain , Helbok Raimund , Helseth Eirik , Horton Lindsay , Huijben Jilske , Hutchinson Peter J. , Jacobs Bram , Jankowski Stefan , Jarrett Mike , Jiang Ji-yao , Johnson Faye , Jones Kelly , Karan Mladen , Kolias Angelos G. , Kompanje Erwin , Kondziella Daniel , Kornaropoulos Evgenios , Koskinen Lars-Owe , Kovács Noémi , Kowark Ana , Lagares Alfonso , Lanyon Linda , Laureys Steven , Lecky Fiona , Ledoux Didier , Lefering Rolf , Legrand Valerie , Lejeune Aurelie , Levi Leon , Lightfoot Roger , Lingsma Hester , Maas Andrew I. R. , Castaño-León Ana M. , Maegele Marc , Majdan Marek , Manara Alex , Manley Geoffrey , Martino Costanza , Maréchal Hugues , Mattern Julia , McMahon Catherine , Melegh Béla , Menovsky Tomas , Mikolic Ana , Misset Benoit , Muraleedharan Visakh , Murray Lynnette , Negru Ancuta , Nelson David , Newcombe Virginia , Nieboer Daan , Nyirádi József , Olubukola Otesile , Ortolano Fabrizio , Palotie Aarno , Parizel Paul M. , Payen Jean-François , Perera Natascha , Perlbarg Vincent , Persona Paolo , Peul Wilco , Piippo-Karjalainen Anna , Pirinen Matti , Ples Horia , Polinder Suzanne , Pomposo Inigo , Posti Jussi P. , Puybasset Louis , Radoi Andreea , Ragauskas Arminas , Raj Rahul , Rambadagalla Malinka , Rhodes Jonathan , Richardson Sylvia , Richter Sophie , Ripatti Samuli , Rocka Saulius , Roe Cecilie , Roise Olav , Rosand Jonathan , Rosenfeld Jeffrey V. , Rosenlund Christina , Rosenthal Guy , Rossaint Rolf , Rossi Sandra , Rueckert Daniel , Rusnák Martin , Sahuquillo Juan , Sakowitz Oliver , Sanchez-Porras Renan , Sandor Janos , Schäfer Nadine , Schmidt Silke , Schoechl Herbert , Schoonman Guus , Schou Rico Frederik , Schwendenwein Elisabeth , Sewalt Charlie , Skandsen Toril , Smielewski Peter , Sorinola Abayomi , Stamatakis Emmanuel , Stanworth Simon , Stevens Robert , Stewart William , Stocchetti Nino , Sundström Nina , Takala Riikka , Tamás Viktória , Tamosuitis Tomas , Taylor Mark Steven , Te Ao Braden , Theadom Alice , Thomas Matt , Tibboel Dick , Timmers Marjolein , Tolias Christos , Trapani Tony , Tudora Cristina Maria , Unterberg Andreas , Vajkoczy Peter , Vallance Shirley , Valeinis Egils , Vámos Zoltán , van der Jagt Mathieu , Van der Steen Gregory , van der Naalt Joukje , van Dijck Jeroen T. J. M. , van Essen Thomas A. , Van Hecke Wim , van Heugten Caroline , Van Praag Dominique , Vyvere Thijs Vande , van Wijk Roel P. J. , Vargiolu Alessia , Vega Emmanuel , Velt Kimberley , Verheyden Jan , Vespa Paul M. , Vik Anne , Vilcinis Rimantas , Volovici Victor , von Steinbüchel Nicole , Voormolen Daphne , Vulekovic Petar , Wiegers Eveline , Williams Guy , Wilson Lindsay , Winzeck Stefan , Wolf Stefan , Yang Zhihui , Ylén Peter , Younsi Alexander , Zeiler Frederick A. , Zelinkova Veronika , Ziverte Agate , Zoerle Tommaso 
Published: May 2022

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.