Depression and antidepressant effects of ketamine and its metabolites: The pivotal role of gut microbiota.
Hao-Ming Hua, Chao Huang, Hanyu Liu, Xiangyang Xu, Xiangqing Xu, Zifeng Wu, Cunming Liu, Yuanyuan Wang, Chun Yang
Neuropharmacology September 1, 2022 DOI: 10.1016/j.neuropharm.2022.109272 via Semantic Scholar
Summary
Ketamine's rapid antidepressant effects, a major advance in depression treatment, may involve the gut-brain axis. This review examines how ketamine and its metabolites interact with the gut microbiome and microbiota-derived molecules. The proposed mechanisms include modulation of the stress response, promotion of brain-derived neurotrophic factor (BDNF)-mediated neurogenesis, anti-inflammatory effects, and regulation of neurotransmitters. However, the exact mechanisms remain unclear.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Keywords | Medicine Biology |
| Citations | 35 |
| Key finding | Ketamine's antidepressant mechanisms may involve bidirectional regulation via the microbiota-gut-brain axis, including stress response, BDNF-mediated neurogenesis, anti-inflammatory effects, and neurotransmitter modulation. |
Abstract
The discovery of the robust antidepressant actions of ketamine is regarded as one of the greatest advancements in depression treatment in the past 60 years. Recent findings have provided strong evidence for the presence of bidirectional communication networks between the gastrointestinal tract and the brain in depression. Moreover, increasing evidence supports the antidepressant role of ketamine in regulating the gut microbiome and microbiota-derived molecules; however, the mechanisms underpinning such effects are still ambiguous. This review summarizes the current understanding of the anti-depressant mechanisms of ketamine and its metabolites regarding the bidirectional regulation by microbiota-gut-brain axis. We review the relationship between gut microbiota and the antidepressant mechanisms of ketamine, and discuss the role of stress response, brain-derived neurotrophic factor (BDNF)-mediated neurogenesis, anti-inflammatory effect and neurotransmitters.