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

38 Pages Posted: 30 May 2019 Sneak Peek Status: Review Complete

See all articles by Eleni Siopi

Eleni Siopi

Institut Pasteur, Perception and Memory Unit; Unité Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique

Grégoire Chevalier

Institut Pasteur, Microenvironment and Immunity Unit; French Institute of Health and Medical Research (INSERM), INSERM U1224

Mathilde Bigot

Institut Pasteur, Perception and Memory Unit; Unité Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique

Lida Katsimpardi

Institut Pasteur, Perception and Memory Unit; Unité Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique

Soham Saha

Institut Pasteur, Perception and Memory Unit; Unité Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique

Carine Moigneu

Institut Pasteur, Perception and Memory Unit; Unité Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique

Gerard Eberl

Institut Pasteur, Microenvironment and Immunity Unit; French Institute of Health and Medical Research (INSERM), INSERM U1224

Pierre-Marie Lledo

Institut Pasteur, Perception and Memory Unit; Unité Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique

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Abstract

Major depressive disorders (MDD) constitute a leading cause of disability worldwide and current pharmacological treatments are partially effective with high relapse rates. The gut microbiota has recently emerged as a potential target of therapeutic interest for MDD, yet the precise mechanisms remain unknown. In the present study, we transferred fecal microbiota from chronically stressed mice to non-stressed recipient mice. We found that chronic stress resulted in gut dysbiosis that was transferable to the recipient mice. The transmitted dysbiosis induced despair-like behavior, decreased hippocampal neurogenesis and weakened the antidepressant and neurogenic effects of a standard selective serotonin reuptake inhibitor, fluoxetine (FLX). These effects were paralleled by a substantial perturbation of key metabolic processes, namely tryptophan metabolism. Supplementation with 5-hydroxytryptophan, the immediate serotonin precursor, restored FLX efficacy and exerted antidepressant effects. Our results reveal that stress-induced changes in gut microbiota are involved in the pathogenesis of depressive disorders and minimize FLX efficacy via perturbations in tryptophan catabolism.

Keywords: gut microbiota, Depression, chronic stress, adult hippocampal neurogenesis, Fluoxetine, tryptophan, metabolism, 5-hydroxytryptophan, serotonin

Suggested Citation

Siopi, Eleni and Chevalier, Grégoire and Bigot, Mathilde and Katsimpardi, Lida and Saha, Soham and Moigneu, Carine and Eberl, Gerard and Lledo, Pierre-Marie, Changes in Gut Microbiota by Chronic Stress Affect the Efficacy of Fluoxetine (May 30, 2019). CELL-REPORTS-D-19-01985. Available at SSRN: https://ssrn.com/abstract=3396132 or http://dx.doi.org/10.2139/ssrn.3396132
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Eleni Siopi (Contact Author)

Institut Pasteur, Perception and Memory Unit ( email )

Paris
France

Unité Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique ( email )

Paris
France

Grégoire Chevalier

Institut Pasteur, Microenvironment and Immunity Unit ( email )

Paris
France

French Institute of Health and Medical Research (INSERM), INSERM U1224 ( email )

Paris
France

Mathilde Bigot

Institut Pasteur, Perception and Memory Unit ( email )

Paris
France

Unité Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique ( email )

Paris
France

Lida Katsimpardi

Institut Pasteur, Perception and Memory Unit ( email )

Paris
France

Unité Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique ( email )

Paris
France

Soham Saha

Institut Pasteur, Perception and Memory Unit ( email )

Paris
France

Unité Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique ( email )

Paris
France

Carine Moigneu

Institut Pasteur, Perception and Memory Unit ( email )

Paris
France

Unité Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique ( email )

Paris
France

Gerard Eberl

Institut Pasteur, Microenvironment and Immunity Unit ( email )

Paris
France

French Institute of Health and Medical Research (INSERM), INSERM U1224 ( email )

Paris
France

Pierre-Marie Lledo

Institut Pasteur, Perception and Memory Unit ( email )

Paris
France

Unité Mixte de Recherche (UMR) MITOVASC, Centre National de la Recherche Scientifique ( email )

Paris
France

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