The impact of gut microbiota on depressive-like behaviors and adult hippocampal neurogenesis requires the endocannabinoid system - Archive ouverte HAL Access content directly
Preprints, Working Papers, ... Year :

The impact of gut microbiota on depressive-like behaviors and adult hippocampal neurogenesis requires the endocannabinoid system

(1) , (2) , (3) , (1, 2) , (3) , (4) , (4) , (3) , (5) , (2) , (1) , (2)
1
2
3
4
5

Abstract

Depression is the leading cause of disability worldwide. Recent observations have revealed an association between mood disorders and alterations of the intestinal microbiota, but causality remains yet to be established. Here, using unpredictable chronic mild stress (UCMS) as a mouse model of depression, we show that the UCMS mice display phenotypic alterations — characterized by an altered gut microbiota composition, a reduced adult hippocampal neurogenesis and a depressive-like behaviors — 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 on adult neurogenesis and behavior in naïve recipient mice were alleviated by selectively enhancing the central eCB tone or by adding arachidonic acid, a fatty acid precursor of eCB ligands, to the diet. In the gut of both UCMS donors and recipients, the microbiota composition was characterized by a relative decrease in Lactobacilli abundance, and complementation of the UCMS recipient microbiota with a strain of the Lactobacilli genus was sufficient to restore normal eCB brain levels, hippocampal neurogenesis and to alleviate depressive-like behaviors. Our findings provide a mechanistic scenario for how chronic stress, diet and gut microbiota dysbiosis generate a pathological feed-forward loop that contributes to despair behavior via the central eCB system.
Fichier principal
Vignette du fichier
718288.full.pdf (8.33 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

pasteur-02873657 , version 1 (11-06-2021)

Licence

Attribution - NonCommercial - NoDerivatives - CC BY 4.0

Identifiers

Cite

Grégoire Chevalier, Eleni Siopi, Laure Guenin-Macé, Maud Pascal, Thomas Laval, et al.. The impact of gut microbiota on depressive-like behaviors and adult hippocampal neurogenesis requires the endocannabinoid system. 2021. ⟨pasteur-02873657⟩
154 View
37 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More