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

Author

Listed:
  • Grégoire Chevalier

    (Institut Pasteur)

  • Eleni Siopi

    (Institut Pasteur)

  • Laure Guenin-Macé

    (Institut Pasteur)

  • Maud Pascal

    (Institut Pasteur
    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)

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.

Suggested Citation

  • 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 , 2020. "Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19931-2
    DOI: 10.1038/s41467-020-19931-2
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    Cited by:

    1. Jordina Balaguer-Trias & Deepika Deepika & Marta Schuhmacher & Vikas Kumar, 2022. "Impact of Contaminants on Microbiota: Linking the Gut–Brain Axis with Neurotoxicity," IJERPH, MDPI, vol. 19(3), pages 1-24, January.

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