Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system

Grégoire Chevalier, Eleni Siopi, Laure Guenin-Macé, Maud Pascal, Thomas Laval, Aline Rifflet, Ivo Gomperts Boneca, Caroline Demangel, Benoit Colsch, Alain Pruvost, Emeline Chu- Van, Aurélie Messager, François Leulier, Gabriel Lepousez, Gérard Eberl () and Pierre-Marie Lledo ()
Additional contact information
Grégoire Chevalier: Institut Pasteur
Eleni Siopi: Institut Pasteur
Laure Guenin-Macé: Institut Pasteur
Maud Pascal: Institut Pasteur
Thomas Laval: Institut Pasteur
Aline Rifflet: Institut Pasteur
Ivo Gomperts Boneca: Institut Pasteur
Caroline Demangel: Institut Pasteur
Benoit Colsch: Université Paris Saclay, CEA, INRAE, Médicaments et Technologie pour la Santé (MTS)
Alain Pruvost: Université Paris Saclay, CEA, INRAE, Médicaments et Technologie pour la Santé (MTS)
Emeline Chu- Van: Université Paris Saclay, CEA, INRAE, Médicaments et Technologie pour la Santé (MTS)
Aurélie Messager: Université Paris Saclay, CEA, INRAE, Médicaments et Technologie pour la Santé (MTS)
François Leulier: Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Ecole Normale Supérieure de Lyon, CNRS UMR 5242
Gabriel Lepousez: Institut Pasteur
Gérard Eberl: Institut Pasteur
Pierre-Marie Lledo: Institut Pasteur

Nature Communications, 2020, vol. 11, issue 1, 1-15

Abstract: Abstract Depression is the leading cause of disability worldwide. Recent observations have revealed an association between mood disorders and alterations of the intestinal microbiota. Here, using unpredictable chronic mild stress (UCMS) as a mouse model of depression, we show that UCMS mice display phenotypic alterations, which could be transferred from UCMS donors to naïve recipient mice by fecal microbiota transplantation. The cellular and behavioral alterations observed in recipient mice were accompanied by a decrease in the endocannabinoid (eCB) signaling due to lower peripheral levels of fatty acid precursors of eCB ligands. The adverse effects of UCMS-transferred microbiota were alleviated by selectively enhancing the central eCB or by complementation with a strain of the Lactobacilli genus. Our findings provide a mechanistic scenario for how chronic stress, diet and gut microbiota generate a pathological feed-forward loop that contributes to despair behavior via the central eCB system.

Date: 2020
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DOI: 10.1038/s41467-020-19931-2

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