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.
Ketamine acts as a rapid and long-lasting antidepressant, but its molecular mechanisms are unclear. In mice subjected to chronic social stress, microRNA miR-98-5p was downregulated in the prefrontal cortex and hippocampus. Overexpressing miR-98-5p with an agonist alleviated depression-like behaviors. Ketamine administration upregulated miR-98-5p, and inhibiting it with an antagonist blocked ketamine's antidepressant effect. This suggests a novel molecular mechanism for ketamine's action and that targeting miR-98-5p could be beneficial for depression treatment.