Serum metabolome associated with severity of acute traumatic brain injury

著者: Ilias Thomas, Alex M. Dickens, Jussi P. Posti, Endre Czeiter, Daniel Duberg, Tim Sinioja, Matilda Kråkström, Isabel R. A. Retel Helmrich, Kevin Wang, Andrew I.R. Maas, Ewout W. Steyerberg, David Menon, Olli Tenovuo, Tuulia Hyötyläinen, András Büki, Matej Orešič, Cecilia Åkerlund, Krisztina Amrein, Nada Anđelić, 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 Bražinová, 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, Giorgio Chevallard, Arturo Chieregato, Giuseppe Citerio, Hans Clusmann, Mark Coburn, Jonathan Coles, Jamie D. Cooper, Marta Correia, Amra Čović, Nicola Curry, Endre Czeiter, Marek Czosnyka, Claire Dahyot‐Fizelier, Paul Dark, Helen Dawes, Véronique De Keyser, Vincent Degos, Françesco Della Corte, Hugo den Boogert, Bart Depreitere, Đula Đilvesi, Abhishek Dixit, Emma Donoghue, Jens P. Dreier, Guy‐Loup Dulière, Ari Ercole, Patrick Esser, Erzsébet Ezer, Martin Fabricius, Valery L. Feigin, Kelly Foks, Shirin Frisvold, Alex Furmanov, Pablo Gagliardo, Damien Galanaud, Dashiell Gantner, Guoyi Gao, Pradeep George, Alexandre Ghuysen, Lelde Giga, Ben Glocker, Jagoš Golubović, Pedro A. Gómez, Johannes Gratz, Benjamin Gravesteijn, Francesca Grossi, Russell L. Gruen, Deepak Gupta, Juanita A. Haagsma, Iain Haitsma, Raimund Helbok, Eirik Helseth, Lindsay Horton, Jilske Huijben, Peter J. Hutchinson, Bram Jacobs, Stefan Jankowski, Mike Jarrett, Jiyao Jiang, Faye Johnson, Kelly Jones, Mladen Karan, Angelos G. Kolias, Erwin J. O. Kompanje, Daniel Kondziella, Evgenios Kornaropoulos, Lars‐Owe Koskinen, Noémi Kovács, Ana Kowark, Alfonso Lagares, Linda Lanyon, Steven Laureys, Fiona Lecky, Didier Ledoux, Rolf Lefering, Valérie Legrand, Aurélie Lejeune, Leon Levi, Roger Lightfoot, Hester F. Lingsma, Andrew I.R. Maas, Ana M. Castaño‐León, Marc Maegele, Marek Majdán, Alex Manara, Geoffrey T. Manley, Costanza Martino, Hugues Maréchal, Julia Mattern, Catherine McMahon, Béla Melegh, Tomas Menovsky, Ana Mikolić, Benoît Misset, Visakh Muraleedharan, Lynnette Murray, Ancuța Negru, David Nelson, Virginia Newcombe, Daan Nieboer, József Nyirádi, Otesile Olubukola, Fabrizio Ortolano, Aarno Palotie, Paul M. Parizel, Jean‐François Payen, Natascha Perera, Vincent Perlbarg, Paolo Persona, Wilco C. Peul, Anna Piippo-Karjalainen, Matti Pirinen, Horia Pleș, Suzanne Polinder, Iñigo Pomposo, Jussi P. Posti, Louis Puybasset, Andreea Rădoi, Arminas Ragauskas, Rahul Raj, Malinka Rambadagalla, Jonathan R. Rhodes, Sylvia Richardson, Sophie Richter, Samuli Ripatti, Saulius Ročka, Cecilie Røe, Olav Røise, Jonathan Rosand, Jeffrey V. Rosenfeld, Christina Rosenlund, Guy Rosenthal, Rolf Rossaint, Sandra Rossi, Daniel Rueckert, Martin Rusňák, Juan Sahuquillo, Oliver Sakowitz, Renán Sánchez-Porras, János Sándor, Nadine Schäfer, Silke Schmidt, Herbert Schöechl, Guus Schoonman, Rico Frederik Schou, Elisabeth Schwendenwein, Charlie Sewalt, Toril Skandsen, Peter Smielewski, Abayomi Sorinola, Emmanuel A. Stamatakis, Simon Stanworth, Robert D. Stevens, William Stewart, Nino Stocchetti, Nina Sundström, Riikka Takala, Viktória Tamás, Tomas Tamošuitis, Mark Taylor, Braden Te Ao, Alice Theadom, Matt Thomas, Dick Tibboel, Marjolein Timmers, Christos Tolias, Tony Trapani, Cristina Maria Tudora, Andreas Unterberg, Peter Vajkoczy, Shirley Vallance, Egils Valeinis, Zoltán Vámos, Mathieu van der Jagt, Gregory Van der Steen, Joukje van der Naalt, Jeroen T.J.M. van Dijck, Thomas A. van Essen, Wim Van Hecke, Caroline van Heugten, Dominique Van Praag, Thijs Vande Vyvere, Roel P. J. van Wijk, Alessia Vargiolu, Emmanuel Vega, Kimberley Velt, Jan Verheyden, Paul Vespa, Anne Vik, Rimantas Vilcinis, Victor Volovici, Nicole von Steinbüchel, Daphne Voormolen, Petar Vuleković, Eveline Wiegers, Guy Williams, Lindsay Wilson, Stefan Winzeck, Stefan Wolf, Zhihui Yang, Peter Ylén, Alexander Younsi, Frederick A. Zeiler, Veronika Zelinkova, Agate Ziverte, Tommaso Zoerle - Nature Communications 2022 被引用: 112

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.