Sofia Cussotto1,2, Conall R Strain1,3, Fiona Fouhy1,3, Ronan G Strain1,3, Veronica L Peterson1,2, Gerard Clarke1,4, Catherine Stanton1,3,4, Timothy G Dinan5,6, John F Cryan7,8. 1. APC Microbiome Ireland, University College Cork, Cork, Ireland. 2. Department of Anatomy and Neuroscience, University College Cork, Room 3.86, Western Gateway Building, Cork, Ireland. 3. Teagasc Food Research Centre, Moorepark, Fermoy, County Cork, Ireland. 4. Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland. 5. APC Microbiome Ireland, University College Cork, Cork, Ireland. t.dinan@ucc.ie. 6. Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland. t.dinan@ucc.ie. 7. APC Microbiome Ireland, University College Cork, Cork, Ireland. j.cryan@ucc.ie. 8. Department of Anatomy and Neuroscience, University College Cork, Room 3.86, Western Gateway Building, Cork, Ireland. j.cryan@ucc.ie.
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.
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.
Authors: Stephan C Bischoff; Reiner Mailer; Oliver Pabst; Gisela Weier; Wanda Sedlik; Zhishan Li; Jason J Chen; Dennis L Murphy; Michael D Gershon Journal: Am J Physiol Gastrointest Liver Physiol Date: 2008-12-18 Impact factor: 4.052
Authors: Thomaz F S Bastiaanssen; Sofia Cussotto; Marcus J Claesson; Gerard Clarke; Timothy G Dinan; John F Cryan Journal: Harv Rev Psychiatry Date: 2020 Jan/Feb Impact factor: 3.732
Authors: Q R Ducarmon; R D Zwittink; B V H Hornung; W van Schaik; V B Young; E J Kuijper Journal: Microbiol Mol Biol Rev Date: 2019-06-05 Impact factor: 11.056
Authors: Sara Vieira-Silva; Jeroen Raes; Mireia Valles-Colomer; Gwen Falony; Youssef Darzi; Ettje F Tigchelaar; Jun Wang; Raul Y Tito; Carmen Schiweck; Alexander Kurilshikov; Marie Joossens; Cisca Wijmenga; Stephan Claes; Lukas Van Oudenhove; Alexandra Zhernakova Journal: Nat Microbiol Date: 2019-02-04 Impact factor: 17.745