Ketamine interactions with gut-microbiota in rats: relevance to its antidepressant and anti-inflammatory properties
Abstract Background Appreciable evidence suggest that dysbiosis in microbiota, reflected in gut microbial imbalance plays a key role in the pathogenesis of neuropsychiatric disorders including depression and inflammatory diseases. Recently, the antidepressant properties of ketamine have gained promi...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-12-01
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| Series: | BMC Microbiology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12866-018-1373-7 |
| _version_ | 1818250443874107392 |
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| author | Bruk Getachew Joseph I. Aubee Richard S. Schottenfeld Antonei B. Csoka Karl M. Thompson Yousef Tizabi |
| author_facet | Bruk Getachew Joseph I. Aubee Richard S. Schottenfeld Antonei B. Csoka Karl M. Thompson Yousef Tizabi |
| author_sort | Bruk Getachew |
| collection | DOAJ |
| description | Abstract Background Appreciable evidence suggest that dysbiosis in microbiota, reflected in gut microbial imbalance plays a key role in the pathogenesis of neuropsychiatric disorders including depression and inflammatory diseases. Recently, the antidepressant properties of ketamine have gained prominence due to its fast and long lasting effects. Additional uses for ketamine in inflammatory disorders such as irritable bowel syndrome have been suggested. However, ketamine’s exact mechanism of action and potential effects on microbiome is not known. Here, we examined the effects of low dose ketamine, known to induce antidepressant effects, on stool microbiome profile in adult male Wistar rats. Animals (5/group) were injected intraperitoneally with ketamine (2.5 mg/kg) or saline, daily for 7 days and sacrificed on day 8 when intestinal stools were collected and stored at − 80 °C. DNA was extracted from the samples and the 16 S rRNA gene-based microbiota analysis was performed using 16S Metagenomics application. Results At genus–level, ketamine strikingly amplified Lactobacillus, Turicibacter and Sarcina by 3.3, 26 and 42 fold, respectively. Conversely, opportunistic pathogens Mucispirillum and Ruminococcus were reduced by approximately 2.6 and 26 fold, respectively, in ketamine group. Low levels of Lactobacillus and Turicibacter are associated with various disorders including depression and administration of certain species of Lactobacillus ameliorates depressive-like behavior in animal models. Hence, some of the antidepressant effects of ketamine might be mediated through its interaction with these gut bacteria. Additionally, high level of Ruminococcus is positively associated with the severity of irritable bowel syndrome (IBS), and some species of Mucispirillum have been associated with intestinal inflammation. Indirect evidence of anti-inflammatory role of Sarcina has been documented. Hence, some of the anti-inflammatory effects of ketamine and its usefulness in specific inflammatory diseases including IBS may be mediated through its interaction with these latter bacteria. Conclusion Our data suggest that at least some of the antidepressant and anti-inflammatory effects of daily ketamine treatment for 7 days may be mediated via its interaction with specific gut bacteria. These findings further validate the usefulness of microbiome as a target for therapeutic intervention and call for more detailed investigation of microbiome interaction with central mediators of mood and/or inflammatory disorders. |
| first_indexed | 2024-12-12T15:52:29Z |
| format | Article |
| id | doaj.art-80a5688b85b744b8b92d483b2c51d443 |
| institution | Directory Open Access Journal |
| issn | 1471-2180 |
| language | English |
| last_indexed | 2024-12-12T15:52:29Z |
| publishDate | 2018-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Microbiology |
| spelling | doaj.art-80a5688b85b744b8b92d483b2c51d4432022-12-22T00:19:35ZengBMCBMC Microbiology1471-21802018-12-0118111010.1186/s12866-018-1373-7Ketamine interactions with gut-microbiota in rats: relevance to its antidepressant and anti-inflammatory propertiesBruk Getachew0Joseph I. Aubee1Richard S. Schottenfeld2Antonei B. Csoka3Karl M. Thompson4Yousef Tizabi5Department of Pharmacology, Howard University College MedicineDepartment of Microbiology, Howard University College MedicineDepartment of Psychiatry and Behavioral Sciences, Howard University College MedicineDepartment of Anatomy, Howard University College MedicineDepartment of Microbiology, Howard University College MedicineDepartment of Pharmacology, Howard University College MedicineAbstract Background Appreciable evidence suggest that dysbiosis in microbiota, reflected in gut microbial imbalance plays a key role in the pathogenesis of neuropsychiatric disorders including depression and inflammatory diseases. Recently, the antidepressant properties of ketamine have gained prominence due to its fast and long lasting effects. Additional uses for ketamine in inflammatory disorders such as irritable bowel syndrome have been suggested. However, ketamine’s exact mechanism of action and potential effects on microbiome is not known. Here, we examined the effects of low dose ketamine, known to induce antidepressant effects, on stool microbiome profile in adult male Wistar rats. Animals (5/group) were injected intraperitoneally with ketamine (2.5 mg/kg) or saline, daily for 7 days and sacrificed on day 8 when intestinal stools were collected and stored at − 80 °C. DNA was extracted from the samples and the 16 S rRNA gene-based microbiota analysis was performed using 16S Metagenomics application. Results At genus–level, ketamine strikingly amplified Lactobacillus, Turicibacter and Sarcina by 3.3, 26 and 42 fold, respectively. Conversely, opportunistic pathogens Mucispirillum and Ruminococcus were reduced by approximately 2.6 and 26 fold, respectively, in ketamine group. Low levels of Lactobacillus and Turicibacter are associated with various disorders including depression and administration of certain species of Lactobacillus ameliorates depressive-like behavior in animal models. Hence, some of the antidepressant effects of ketamine might be mediated through its interaction with these gut bacteria. Additionally, high level of Ruminococcus is positively associated with the severity of irritable bowel syndrome (IBS), and some species of Mucispirillum have been associated with intestinal inflammation. Indirect evidence of anti-inflammatory role of Sarcina has been documented. Hence, some of the anti-inflammatory effects of ketamine and its usefulness in specific inflammatory diseases including IBS may be mediated through its interaction with these latter bacteria. Conclusion Our data suggest that at least some of the antidepressant and anti-inflammatory effects of daily ketamine treatment for 7 days may be mediated via its interaction with specific gut bacteria. These findings further validate the usefulness of microbiome as a target for therapeutic intervention and call for more detailed investigation of microbiome interaction with central mediators of mood and/or inflammatory disorders.http://link.springer.com/article/10.1186/s12866-018-1373-7NMDA receptorLactobacillusTuricibacterRuminococcusSarcinaMucispirillum |
| spellingShingle | Bruk Getachew Joseph I. Aubee Richard S. Schottenfeld Antonei B. Csoka Karl M. Thompson Yousef Tizabi Ketamine interactions with gut-microbiota in rats: relevance to its antidepressant and anti-inflammatory properties BMC Microbiology NMDA receptor Lactobacillus Turicibacter Ruminococcus Sarcina Mucispirillum |
| title | Ketamine interactions with gut-microbiota in rats: relevance to its antidepressant and anti-inflammatory properties |
| title_full | Ketamine interactions with gut-microbiota in rats: relevance to its antidepressant and anti-inflammatory properties |
| title_fullStr | Ketamine interactions with gut-microbiota in rats: relevance to its antidepressant and anti-inflammatory properties |
| title_full_unstemmed | Ketamine interactions with gut-microbiota in rats: relevance to its antidepressant and anti-inflammatory properties |
| title_short | Ketamine interactions with gut-microbiota in rats: relevance to its antidepressant and anti-inflammatory properties |
| title_sort | ketamine interactions with gut microbiota in rats relevance to its antidepressant and anti inflammatory properties |
| topic | NMDA receptor Lactobacillus Turicibacter Ruminococcus Sarcina Mucispirillum |
| url | http://link.springer.com/article/10.1186/s12866-018-1373-7 |
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