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© Research
Publication : Cell reports

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Cell reports - 17 Mar 2020

Siopi E, Chevalier G, Katsimpardi L, Saha S, Bigot M, Moigneu C, Eberl G, Lledo PM,

Link to Pubmed [PMID] – 32187541

Link to DOI – S2211-1247(20)30273-410.1016/j.celrep.2020.02.099

Cell Rep 2020 03; 30(11): 3682-3690.e6

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.

https://pubmed.ncbi.nlm.nih.gov/32187541