Ketamine enantiomers and the gut microbiota: mechanisms, clinical implications, and future directions.
Jin-Xi Xie, Li-Wen Zhou
Molecular Biology Reports December 10, 2025 DOI: 10.1007/s11033-025-11357-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression Esketamine Ketamine |
| Keywords | Gut brain axis Gut microbiota |
| Key findings | Proposes that esketamine's rapid antidepressant effect may involve modulation of gut microbiota, and that ketamine isomers and racemic mixtures may affect gut bacteria via anti-inflammatory effects, neurotransmitter metabolism regulation, and intestinal barrier repair. The authors outline clinical implications and future research directions for this gut-brain axis interaction. |
Abstract
There is a complex, bidirectional interaction between the gut microbiota and the central nervous system, known as the gut-brain axis. Esketamine, as the right-handed isomer of ketamine, has been approved by the US FDA for the treatment of treatment-resistant depression (TRD), and its rapid antidepressant effect may involve modulation of gut microbiota. In addition, other ketamine isomers (such as R-ketamine) and racemic mixtures (R, S-ketamine) may also affect the gut microbiota through different pathways. This article reviews the potential regulatory mechanisms of ketamine and its isomers on gut microbiota, including anti-inflammatory effects, regulation of neurotransmitter metabolism, and intestinal barrier repair. It discusses, their clinical implications and future research directions.
Comparable studies
Other narrative reviews on esketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Long-term safety of ketamine and esketamine in treatment of depression | 2022 | Review | |
| Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. | 2024 | Review | |
| Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review. Patients with depression | 2024 | Narrative review | |
| The Possible Application of Ketamine in the Treatment of Depression in Alzheimer’s Disease | 2022 | Review |
Citations in the library
Cites 25
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- NMDAR inhibition-independent antidepressant actions of ketamine metabolites Nature April 24, 2016
- Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms Pharmacological Reviews June 26, 2018
- Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression JAMA Psychiatry June 5, 2019
and 20 more in the library