Differential effects of psychotropic drugs on microbiome composition and gastrointestinal function
Abstract
Rationale Growing evidence supports a role for the microbiota in regulating gut-brain interactions and, thus, psychiatric disorders. Despite substantial scientific efforts to delineate the mechanism of action of psychotropic medications at a central nervous system (CNS) level, there remains a critical lack of understanding on how these drugs might affect the microbiota and gut physiology. Objectives We investigated the antimicrobial activity of psychotropics against two bacterial strain residents in the human gut, Lactobacillus rhamnosus and Escherichia coli. In addition, we examined the impact of chronic treatment with these drugs on microbiota and intestinal parameters in the rat. Results In vitro fluoxetine and escitalopram showed differential antimicrobial effects. Lithium, valproate and aripiprazole administration significantly increased microbial species richness and diversity, while the other treatments were not significantly different from controls. At the genus level, several species belonging to Clostridium, Peptoclostridium, Intestinibacter and Christenellaceae were increased following treatment with lithium, valproate and aripiprazole when compared to the control group. Animals treated with escitalopram, venlafaxine, fluoxetine and aripiprazole exhibited an increased permeability in the ileum. Conclusions These data show that psychotropic medications differentially influence the composition of gut microbiota in vivo and that fluoxetine and escitalopram have specific antimicrobial activity in vitro. Interestingly, drugs that significantly altered gut microbial composition did not increase intestinal permeability, suggesting that the two factors are not causally linked. Overall, unravelling the impact of psychotropics on gastrointestinal and microbiota measures offers the potential to provide critical insight into the mechanism of action and side effects of these medications.
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- Authors
- Cussotto, S., Strain, C. R., Fouhy, F., Strain, R. G., Peterson, V. L., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F.
- Affiliations
- University College Cork (IE)
- Teagasc - The Irish Agriculture and Food Development Authority (IE)
- Corresponding author
- Dinan, Timothy G.
- Cryan, John F.
- ORCID
- Venue
- Psychopharmacology
- Published
- 2018-08-28
- Volume
- 236
- Issue
- 5
- Pages
- 1671-1685
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2889513832
- Cited by
- 266
- References
- 19
- Citations by year
- 2026: 21 · 2025: 24 · 2024: 40 · 2023: 38 · 2022: 40 · 2021: 23 · 2020: 30 · 2019: 44 · 2018: 5
- FWCI
- 9.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Science Foundation Ireland (12/RC/2273)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Keywords
- psychotropic drugs, gut microbiota, gut-brain axis, fluoxetine, escitalopram, lithium, valproic acid, aripiprazole, venlafaxine, antimicrobial activity, Lactobacillus rhamnosus, Escherichia coli, intestinal permeability, microbial diversity, Clostridium
- MeSH terms
- Gastrointestinal Microbiome, Animals, Anti-Bacterial Agents, Dose-Response Relationship, Drug, Escherichia coli, Humans, Male, Psychotropic Drugs, Rats, Sprague-Dawley, Gastrointestinal Tract, Rats, Lacticaseibacillus rhamnosus
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