Laboratory of Nutritional Psychiatry, Institute of Neuroscience, UCLouvain, Université catholique de Louvain, Brussels, Belgium
Hany Ahmed
Food Sciences Unit, Department of Life Technologies, University of Turku, Turku, Finland
Camille Amadieu
Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium
Géraldine Petit
Department of Adult Psychiatry, Cliniques Universitaires Saint-Luc and Institute of Neuroscience, UCLouvain, Université catholique de Louvain, Brussels, Belgium
Ville Koistinen
Food Sciences Unit, Department of Life Technologies, University of Turku, Turku, Finland; School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
Metabolism and Nutrition Research Group, Louvain Drug Research Institute, UCLouvain, Université catholique de Louvain, Brussels, Belgium; Université de Bordeaux, INRAE, Bordeaux INP, NutriNeurO, UMR 1286, Bordeaux, France
Marie Poncin
Department of Adult Psychiatry, Cliniques Universitaires Saint-Luc and Institute of Neuroscience, UCLouvain, Université catholique de Louvain, Brussels, Belgium
Peter Stärkel
Department of gastro-enterology, Cliniques Universitaires Saint Luc, Brussels, Belgium
Department of Pathology, University of Helsinki, Helsinki, Finland; Faculty of Medicine and Health Technology, Tampere University and Fimlab Laboratories, Tampere, Finland
Pekka J Karhunen
Faculty of Medicine and Health Technology, Tampere University and Fimlab Laboratories, Tampere, Finland
Philippe de Timary
Department of Adult Psychiatry, Cliniques Universitaires Saint-Luc and Institute of Neuroscience, UCLouvain, Université catholique de Louvain, Brussels, Belgium
Sophie Laye
Université de Bordeaux, INRAE, Bordeaux INP, NutriNeurO, UMR 1286, Bordeaux, France
School of Pharmacy, University of Eastern Finland, Kuopio, Finland
Kati Hanhineva
Food Sciences Unit, Department of Life Technologies, University of Turku, Turku, Finland; School of Medicine, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
Background: Alcohol use disorder (AUD) is a global health problem with limited therapeutic options. The biochemical mechanisms that lead to this disorder are not yet fully understood, and in this respect, metabolomics represents a promising approach to decipher metabolic events related to AUD. The plasma metabolome contains a plethora of bioactive molecules that reflects the functional changes in host metabolism but also the impact of the gut microbiome and nutritional habits. Methods: In this study, we investigated the impact of severe AUD (sAUD), and of a 3-week period of alcohol abstinence, on the blood metabolome (non-targeted LC-MS metabolomics analysis) in 96 sAUD patients hospitalized for alcohol withdrawal. Results: We found that the plasma levels of different lipids ((lyso)phosphatidylcholines, long-chain fatty acids), short-chain fatty acids (i.e. 3-hydroxyvaleric acid) and bile acids were altered in sAUD patients. In addition, several microbial metabolites, including indole-3-propionic acid, p-cresol sulfate, hippuric acid, pyrocatechol sulfate, and metabolites belonging to xanthine class (paraxanthine, theobromine and theophylline) were sensitive to alcohol exposure and alcohol withdrawal. 3-Hydroxyvaleric acid, caffeine metabolites (theobromine, paraxanthine, and theophylline) and microbial metabolites (hippuric acid and pyrocatechol sulfate) were correlated with anxiety, depression and alcohol craving. Metabolomics analysis in postmortem samples of frontal cortex and cerebrospinal fluid of those consuming a high level of alcohol revealed that those metabolites can be found also in brain tissue. Conclusions: Our data allow the identification of neuroactive metabolites, from interactions between food components and microbiota, which may represent new targets arising in the management of neuropsychiatric diseases such as sAUD. Funding: Gut2Behave project was initiated from ERA-NET NEURON network (Joint Transnational Call 2019) and was financed by Academy of Finland, French National Research Agency (ANR-19-NEUR-0003-03) and the Fonds de la Recherche Scientifique (FRS-FNRS; PINT-MULTI R.8013.19, Belgium). Metabolomics analysis of the TSDS samples was supported by grant from the Finnish Foundation for Alcohol Studies.
