Changes in Gut Microbiota by Chronic Stress Impair the Efficacy of Fluoxetine
Open accessAbstract
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.
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FMT from CUMS mice to germ-free mice resulted in increased anxiety and depression-like behaviour in three studies.
“When investigating the effects of FMT from CUMS mice to germ free mice, three studies found that the FMT resulted in increased anxiety and depression-like behaviour [21–23].”
From Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review (2020) · cites this paper as [23]
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References 36 · Cited by 116
- Authors
- Siopi, E., Chevalier, G., Katsimpardi, L., Saha, S., Bigot, M., Moigneu, C., Eberl, G., & Lledo, P.-M.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Corresponding author
- Siopi, Eleni
- Lledo, Pierre-Marie
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2020-03
- Volume
- 30
- Issue
- 11
- Pages
- 3682-3690.e6
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W3012313023
- Cited by
- 116
- References
- 36
- Citations by year
- 2026: 12 · 2025: 6 · 2024: 34 · 2023: 17 · 2022: 19 · 2021: 20 · 2020: 8
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fondation des Gueules Cassées
- Agence Nationale de la Recherche (ANR-11-IDEX-0004-02, ANR-10-LABX-73, ANR-15-CE37-0004-01)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- gut microbiota, chronic stress, fluoxetine, major depressive disorder, antidepressant efficacy, hippocampal neurogenesis, serotonin, 5-hydroxytryptophan, tryptophan metabolism, fecal microbiota transplantation, despair-like behavior, selective serotonin reuptake inhibitors
- MeSH terms
- Gastrointestinal Microbiome, Animals, Antidepressive Agents, Cell Differentiation, Chronic Disease, Depression, Fluoxetine, Hippocampus, 5-Hydroxytryptophan, Male, Mice, Inbred C57BL, Serotonin, Stress, Psychological, Tryptophan, Treatment Outcome, Neurogenesis, Neural Stem Cells
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