Major depressive disorder (MDD) is one of the severe mental illness caused by genetic and environmental interactions.There are several hypotheses that sought to account for this disorder.However,none of them is widely recognized.Gut microbiome,the largest and most direct external environment for human body,is considered as a new focus in the research of MDD.Based on the new development,we will summarize the following aspects of MDD in this article:(1) How the gut microbiome shapes the brain neurochemistry and behaviors through microbiota-gut-brain axis?(2) Association between disturbances of gut microbiome and MDD;(3) The potential pathogenesis of gut microbiome in the onset of MDD;(4) The prospects of developing new diagnosis and treatment for MDD by targeting microbiota-gut-brain axis.