BACKGROUND: Growing attention has been paid to the field of gut microbiota for mental disorders over the last decade. However, to our knowledge, no studies have conducted systematic reviews on the association between gut microbiota and major depressive disorder (MDD) in both interventional and non-interventional studies. METHODS: We conducted a systematic review and meta-analysis of 16 studies (10 observational [701 participants] and six interventional trials [302 participants]) examining gut microbiota in patients with MDD. The primary outcome measures were differences in the profile of microbiota in the observational studies, and symptom changes for depression between pre- and post-intervention with probiotics in the interventional trials. RESULTS: In the observational studies, significant reductions in several taxa at the family and genus levels were observed in patients with MDD compared to non-depressed controls. In the interventional studies with probiotics, a significant improvement was found in depressive symptomatology compared to controls (SMD = -1.62, 95% CI = -2.73 to -0.51, p< 0.01). LIMITATIONS: Lack of consideration of the effects of diet and pharmacotherapy was a possible limitation. CONCLUSIONS: Our results indicate that several taxa at the family and genus levels, specifically family Prevotellaceae, genus Corprococcus, and Faecalibacterium, were decreased in MDD compared to non-depressed controls in observational studies, and depressive symptoms were improved compared to controls in interventional studies with probiotics. Due to the limited number of studies, further studies considering diet and pharmacotherapy are needed to explore the relationships between gut microbiota and MDD in humans.