Changes in Gut Microbiota by Chronic Stress Impair the Efficacy of Fluoxetine - PubMed (original) (raw)

. 2020 Mar 17;30(11):3682-3690.e6.

doi: 10.1016/j.celrep.2020.02.099.

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

Eleni Siopi et al. Cell Rep. 2020.

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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.

Keywords: 5-hydroxytryptophan; adult hippocampal neurogenesis; chronic stress; depression; fluoxetine; gut microbiota; serotonin; tryptophan.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

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Conflict of interest statement

Declaration of Interests The authors declare no competing interests.

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