Neuroinflammation through the vagus nerve-dependent gut-microbiota-brain axis in treatment-resistant depression.

Abstract

Neuroinflammation plays a key role in the pathogenesis of major depressive disorder (MDD), including treatment-resistant depression (TRD). Patients with TRD have higher levels of inflammatory biomarkers compared with responders to antidepressants. Multiple lines of evidence suggest that the gut-microbiota-brain axis via the vagus nerve plays a key role in neuroinflammation. Preclinical and clinical data suggest that fecal microbiota transplantation (FMT) from MDD patients or rodents with depression-like behaviors cause depression-like behaviors in rodents through systemic inflammation. Importantly, subdiaphragmatic vagotomy blocked these depression-like phenotypes and systemic inflammation in rodents after FMT of depression-related microbes. Subdiaphragmatic vagotomy also blocked the antidepressant-like effects of serotonergic antidepressants in rodents. Preclinical findings suggest that the new antidepressant, (R)-ketamine (or arketamine), may restore the altered composition of gut microbiota in rodents with depression-like behaviors, contributing to the beneficial effects of arketamine. In this chapter, the author reviews the role of the vagus nerve-dependent gut-microbiota-brain axis in depression (including TRD), and also discuss the potential of FMT, vagus nerve stimulation, and arketamine for the treatment of TRD.