In this study, feces from 19 cases of major depressive disorder (MDD) and 20 healthy individuals were collected for 16S rRNA high-throughput sequencing, in order to investigate the gut microbiota profile of depression and whether gut microbiota can be a predictor of depression. Participants’ assessment scores for patient health questionnaire (PHQ-9) and generalized anxiety disorder (GAD-7) were analyzed in relation to the different microbiota between the two groups. No significant difference in alpha diversity was found in depressed compared to healthy individuals. Differential species analysis revealed a significant enrichment of six signature microorganisms in the depression group, including Finegoldia, Lactiaseibacillus, Enterobacterales, Enterobacteriaceae, Fusicatenilbacter, and Clostridia. Significant enrichment of Coprococcus in the healthy group was significantly and negatively correlated with levels of depression and anxiety. The structure and composition of the gut flora of patients with depression were resolved based on high-throughput sequencing of gut microbial 16SrRNA, which provided potential microbial markers for the alleviation of clinical symptoms of depression.