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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Acknowledgments

The authors gratefully acknowledge Pat Fitzgerald, Gonzalo Rabasa, Karen Scott, Gilliard Lach, Gerry Moloney, Anna Golubeva and Kieran Rea for their invaluable support. We would also like to acknowledge Wiley Barton for his assistance in R scripts and the Teagasc Sequencing Facility, Dr. Paul Cotter, Dr. Fiona Crispie and Ms. Laura Finnegan.

Funding

APC Microbiome Ireland is a research centre funded by Science Foundation Ireland (SFI), through the Irish Government’s National Development Plan (grant no. 12/RC/2273). JFC, TGD and CS have research funding from Dupont Nutrition Biosciences APS, Cremo SA, Alkermes Inc., 4D Pharma PLC, Mead Johnson Nutrition, Nutricia Danone, Suntory Wellness. JFC, TGD, CS and GC have spoken at meetings sponsored by food and pharmaceutical companies.

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Correspondence to Timothy G. Dinan or John F. Cryan.

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Experiments were conducted in accordance with the European Directive 2010/63/EU. Approval by the Animal Experimentation Ethics Committee of University College Cork was obtained before commencement of all animal-related experiments.

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All other authors declare that they have no conflict of interest.

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This article belongs to a Special Issue on Microbiome in Psychiatry & Psychopharmacology.

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Cussotto, S., Strain, C.R., Fouhy, F. et al. Differential effects of psychotropic drugs on microbiome composition and gastrointestinal function. Psychopharmacology 236, 1671–1685 (2019). https://doi.org/10.1007/s00213-018-5006-5

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Keywords

  • Psychotropics
  • Intestinal permeability
  • Gut microbiota
  • Diversity
  • Richness
  • Short-chain fatty acids
  • Antimicrobial