Objective To explore the differences in intestinal microbiota species between patients with depression and healthy controls， providing reference for the diagnosis and treatment of depression. Methods A total of 53 patients with depression who visited the psychiatric department of Zhuzhou Third Hospital from November 2020 to November 2022 were selected as the depression group. At the same time， 55 healthy volunteers matched in gender and age were publicly recruited as the health control group in Zhuzhou City. General data were collected. The fresh feces from subjects were collected. 16S rDNA metagene sequencing was applied to analyze the differences in intestinal microbiota diversity， abundance， structure and correlation with clinical symptoms. Results A total of 27 237 978 16s rDNA were collected. The α diversity analysis of the overall abundance of intestinal microbiota showed that there was no significant difference between the two groups （P ＞ 0.05）. In terms of species and structure， the β diversity analysis of four distances （Jaccard distance， Bray-Curtis distance， unweighted UniFrac distance， and weighted UniFrac distance） showed that the differences between the two groups were statistically significant （all P ＜ 0.05）. Compared with the healthy control group， the proportion of Bacteroidetes in the depression group increased （12.4% vs. 44.1%）， and the ratio of Firmicutes to Bacteroidetes （F/B） decreased （6.35 vs. 1.04）. Linear discriminant analysis effect size （LEfSe） analysis showed that， as many as 30 species of gut microbiota were statistically different between the two groups （P＜ 0.05， LDA＞ 2）. Conclusions There are differences in intestinal microbiota between patients with depression and healthy controls， and the different gut microbiota species may be used as potential objective markers and intervention targets.