Brain–gut–microbiota axis in depression: A historical overview and future directions

Depression is the most common mental disorder and a leading cause of disability worldwide. Despite abundant research, the precise mechanisms underlying the pathophysiology of depression remain elusive. Accumulating evidence from preclinical and clinical studies suggests that alterations in the gut microbiota, microbe-derived short-chain fatty acids, D-amino acids and metabolites play a key role in the pathophysiology of depression via the brain–gut–microbiota axis, including the neural and immune systems. Notably, the brain–gut–microbiota axis might play a crucial role in susceptibility versus resilience in rodents exposed to stress. Vagotomy is reported to block depression-like phenotypes in rodents after fecal microbiota transplantation of "depression-related" microbiome, suggesting that the vagus nerve influences depression through the brain–gut–microbiota axis. In this article, we review recent findings regarding the brain–gut–microbiota axis in depression and discuss its potential as a therapeutic target for depression.