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Journal Articles Cell Reports Year : 2020

Changes in Gut Microbiota by Chronic Stress Impair the Efficacy of Fluoxetine

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Abstract

Major depressive disorders (MDDs) constitute a leading cause of disability worldwide and current pharmacological treatments are partially effective. The gut microbiota (GM) has recently emerged as a target of therapeutic interest for MDDs. In this study, we transfer GM from mice that sustained unpredictable chronic mild stress (UCMS) to healthy recipient mice. The fecal transfer induces despair-like behavior, decreases neurogenesis in the hippocampus (HpC), and impairs the antidepressant and neurogenic effects of a standard selective serotonin (5-HT) reuptake inhibitor, fluoxetine (FLX). These effects are paralleled by deficits in 5-HT bioavailability, biosynthesis, and reuptake in the HpC. Treatment with 5-hydroxytryptophan restores the levels of 5-HT and its precursors in the HpC, improves HpC neurogenesis, and alleviates despair-like symptoms. Our results reveal that stress-induced changes in GM are involved in the pathogenesis of depressive disorders and minimize FLX efficacy via alterations in the serotonergic pathway of Trp metabolism.
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Origin : Publication funded by an institution

Dates and versions

pasteur-03257987 , version 1 (11-06-2021)

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Attribution - NonCommercial - NoDerivatives - CC BY 4.0

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Eleni Siopi, Grégoire Chevalier, Lida Katsimpardi, Soham Saha, Mathilde Bigot, et al.. Changes in Gut Microbiota by Chronic Stress Impair the Efficacy of Fluoxetine. Cell Reports, 2020, 30 (11), pp.3682 - 3690.e6. ⟨10.1016/j.celrep.2020.02.099⟩. ⟨pasteur-03257987⟩
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