Changes in Gut Microbiota by Chronic Stress Impair the Efficacy of Fluoxetine.
5-Hydroxytryptophan
/ metabolism
Animals
Antidepressive Agents
/ pharmacology
Cell Differentiation
/ drug effects
Chronic Disease
Depression
/ drug therapy
Fluoxetine
/ pharmacology
Gastrointestinal Microbiome
/ drug effects
Hippocampus
/ drug effects
Male
Mice, Inbred C57BL
Neural Stem Cells
/ drug effects
Neurogenesis
/ drug effects
Serotonin
/ biosynthesis
Stress, Psychological
/ blood
Treatment Outcome
Tryptophan
/ metabolism
5-hydroxytryptophan
adult hippocampal neurogenesis
chronic stress
depression
fluoxetine
gut microbiota
serotonin
tryptophan
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
17 03 2020
17 03 2020
Historique:
received:
17
05
2019
revised:
25
11
2019
accepted:
26
02
2020
entrez:
19
3
2020
pubmed:
19
3
2020
medline:
24
3
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32187541
pii: S2211-1247(20)30273-4
doi: 10.1016/j.celrep.2020.02.099
pii:
doi:
Substances chimiques
Antidepressive Agents
0
Fluoxetine
01K63SUP8D
Serotonin
333DO1RDJY
Tryptophan
8DUH1N11BX
5-Hydroxytryptophan
C1LJO185Q9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3682-3690.e6Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.