Major depressive disorder is the leading cause of disability worldwide, and its pathophysiology remains incompletely understood. The gut microbiome, acting through the gut–microbiota–brain axis, is an increasingly recognized environmental factor in depression. Available treatments are insufficient, as 30% of patients are treatment-resistant, creating a need for novel strategies. Ketamine is an effective antidepressant in treatment-resistant patients, and its effects may be partially mediated by modification of gut microbiota. This review examines data on gut microbiota in depression, focusing on ketamine's effects on the microbiome in animal models. Earlier reports are preliminary and insufficient for firm conclusions, but further studies could clarify the gut–brain axis's role in depression treatment and lead to new strategies.
In people with treatment-resistant depression, a single intravenous dose of ketamine (0.5 mg/kg) produces rapid, temporary shifts in immune markers. Within 4 hours, total T cells and certain helper T-cell subsets increased, while by 24 hours, activated T cells declined and the ratio of helper to cytotoxic T cells decreased. Blood levels of the anti-inflammatory cytokine IL-10 rose, while the pro-inflammatory cytokines IL-6 and IL-8 fell—IL-8 remained lower for at least 24 hours. In laboratory experiments, high-dose ketamine boosted the growth of helper T cells from depressed patients and increased secretion of IL-8 and IL-6 from activated immune cells. The sustained drop in IL-8 points to an anti-inflammatory effect and may serve as a biomarker for treatment response.