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Paroxetine Administration Affects Microbiota and Bile Acid Levels in Mice
Frederik Dethloff1, Fernando Vargas2,3,4, Emmanuel Elijah2,3
1Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.
Abstract:
Recent interest in the role of microbiota in health and disease has implicated gut microbiota dysbiosis in psychiatric disorders including major depressive disorder. Several antidepressant drugs that belong to the class of selective serotonin reuptake inhibitors have been found to display antimicrobial activities. In fact, one of the first antidepressants discovered serendipitously in the 1950s, the monoamine-oxidase inhibitor Iproniazid, was a drug used for the treatment of tuberculosis. In the current study we chronically treated DBA/2J mice for 2 weeks with paroxetine, a selective serotonin reuptake inhibitor, and collected fecal pellets as a proxy for the gut microbiota from the animals after 7 and 14 days. Behavioral testing with the forced swim test revealed significant differences between paroxetine- and vehicle-treated mice. Untargeted mass spectrometry and 16S rRNA profiling of fecal pellet extracts showed several primary and secondary bile acid level, and microbiota alpha diversity differences, respectively between paroxetine- and vehicle-treated mice, suggesting that microbiota functions are altered by the drug. In addition to their lipid absorbing activities bile acids have important signaling activities and have been associated with gastrointestinal diseases and colorectal cancer. Antidepressant drugs like paroxetine should therefore be used with caution to prevent undesirable side effects.
Insights
Selective serotonin reuptake inhibitor (SSRI) antidepressants like paroxetine alter gut microbiota and bile acid profiles in mice. These findings suggest potential side effects impacting gut health and warrant cautious use of SSRIs.
Area of Science:
- Neuroscience
- Microbiology
- Pharmacology
Background:
- Gut microbiota dysbiosis is linked to psychiatric disorders like major depressive disorder.
- Some antidepressants, including SSRIs, exhibit antimicrobial properties.
- The historical link between tuberculosis treatment and early antidepressants highlights drug-microbe interactions.
Purpose of the Study:
- To investigate the effects of chronic paroxetine treatment on gut microbiota composition and function in mice.
- To assess behavioral changes associated with paroxetine administration.
- To explore alterations in bile acid metabolism due to paroxetine exposure.
Main Methods:
- DBA/2J mice were treated with paroxetine or vehicle for two weeks.
- Fecal samples were collected at 7 and 14 days for analysis.
- Behavioral testing (forced swim test), untargeted mass spectrometry (bile acids), and 16S rRNA profiling (microbiota diversity) were performed.
Main Results:
- Paroxetine treatment induced significant behavioral differences compared to controls.
- Alterations in primary and secondary bile acid levels were observed.
- Significant differences in gut microbiota alpha diversity were detected between treated and untreated groups.
Conclusions:
- Chronic paroxetine administration impacts gut microbiota composition and function, including bile acid profiles.
- These drug-induced changes suggest potential mechanisms for side effects.
- Caution is advised when using SSRIs due to potential undesirable effects on gut health.
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