Related Experiment Video
Updated: Dec 26, 2025
The Unpredictable Chronic Mild Stress Protocol for Inducing Anhedonia in Mice
Published on: October 24, 2018
Changes in Gut Microbiota by Chronic Stress Impair the Efficacy of Fluoxetine
Eleni Siopi1, Grégoire Chevalier2, Lida Katsimpardi1
1Institut Pasteur, Perception and Memory Unit, 75015 Paris, France; Centre National de la Recherche Scientifique (CNRS), Unité Mixte de Recherche 3571, 75015 Paris, France.
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.
Insights
Stress-induced changes in gut microbiota (GM) can cause depression-like behaviors and reduce the effectiveness of antidepressants like fluoxetine (FLX). Restoring serotonin levels with 5-hydroxytryptophan can reverse these effects.
Area of Science:
- Neuroscience
- Microbiology
- Pharmacology
Background:
- Major depressive disorders (MDDs) are a leading cause of global disability with limited treatment efficacy.
- The gut microbiota (GM) is a novel therapeutic target for MDDs.
- Stress significantly impacts both GM composition and mental health.
Purpose of the Study:
- To investigate the causal role of stress-induced GM alterations in MDD pathogenesis.
- To determine the impact of GM transfer on depressive behaviors and neurogenesis.
- To elucidate the mechanisms by which GM affects antidepressant efficacy.
Main Methods:
- Fecal microbiota transplantation from stress-exposed mice to healthy recipients.
- Assessment of despair-like behavior and hippocampal neurogenesis.
- Analysis of serotonin (5-HT) metabolism and bioavailability in the hippocampus.
- Evaluation of 5-hydroxytryptophan (5-HTP) treatment efficacy.
Main Results:
- Microbiota transfer induced despair-like behavior and reduced hippocampal neurogenesis.
- Stress-induced GM impaired fluoxetine's antidepressant and neurogenic effects.
- Serotonergic pathway deficits (5-HT bioavailability, biosynthesis, reuptake) were observed.
- 5-HTP treatment restored 5-HT levels, improved neurogenesis, and alleviated depressive symptoms.
Conclusions:
- Stress-induced gut microbiota alterations contribute to MDD development.
- GM modulates the efficacy of selective serotonin reuptake inhibitors (SSRIs) by affecting the serotonergic pathway.
- Targeting the gut microbiota and serotonin metabolism offers a potential therapeutic strategy for MDDs.
More Related Videos
Related Concept Videos
01:30Stress and Mental Health
Individuals with depression often experience challenges in both their personal and professional...
01:17Irritable Bowel Syndrome I: Introduction
IBS is a chronic condition that can persist over a long period or recur frequently.
The pathogenesis of IBS involves a complex interplay of the following factors:
Altered...
01:23Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists