Fig. 1: Gut microbial composition, short chain fatty acids (SCFAs) and inflammatory indicators of patients with MDD.

A Alpha-diversity analysis exposed that the Chao index, Faith’s Phylogenetic Diversity (PD), Observed species were higher in MDD patients (n = 85) than in HCs (n = 85), The Good’s coverage was lower in MDD patients (P < 0.05). Two-sample T test was used. Data are presented as mean values with SD. Box plots indicate median and interquartile range. B Beta diversity analysis uncovered that the difference between MDD patients (n = 85) and in HCs (n = 85) was larger than the difference within group by the permanova analysis based on Jaccard dissimilarity (P = 0.0006). Permutation test was used. Data are presented as mean values with SD. Box plots indicate median and interquartile range. The upper and lower whiskers indicate minima and maxima. C A linear discriminant analysis (LDA) effect size (LEfSe) showed that at the family level, the relative abundance of Micromonosporaceae and Rhodospirillaceae was significantly higher in MDD patients, however, the amount of Clostridiaceae, Peptostreptococcaceae, Pasteurellaceaewas and Turicibacteraceae significantly higher in HCs. At the genus level, the relative abundance of Adlercreutzia was significantly higher in MDD patients, however, the abundance of Clostridium, Roseburia, Haemophilus, SMB53, and Turicibacter were much higher in HCs. Blue and red colors represent HCs and MDD, respectively. D The correlation analysis were performed among different genus of gut bacteria, short chain fatty acids (SCFAs), hs-CRP and severity of depression and anxiety. It was found the relative abundance of Clostridium, Roseburia, Haemophilus, SMB53, and Turicibacter were the level of Acetic acid, Propionic acid and Butyric acid were positively correlated with Propionic acid and Butyric acid, and negatively correlated with hs-CRP and the total score HAMD-17 in all subjects (P < 0.05). The hs-CRP was positively correlated with the total score HAMD-17 and HAMA (P < 0.05). Pearson correlation analyses were implemented with FDR correction. The red and blue of the table represent positive and negative correlations respectively. P-value is marked as follows: ***P ≤ 0.001; **P ≤ 0.01; *P ≤ 0.05. E Different cytokine in intestinal mucosa between MDD (n = 6) and HCs (n = 6). The antibody cytokine array consisting of 80 inflammatory factors was used to screen for differential intestinal mucosal inflammatory factors between MDD and HCs. The heatmap shows that tumor necrosis factor alpha-R1 (TNF-R1), TNF-R2, Macrophage Colony Stimulating Factor (MCSF) and interleukin 12 (IL-12) are overexpressed, however, Growth Hormone (GH), Fibroblast Growth Factors 4 (FGF-4), Transforming Growth Factor 1β (TGF-1β) and Endocrine Gland-derived Vascular Endothelial Growth Factor (EG-VEGF) that involved in intestinal mucosal repair are underexpressed in MDD patients compared to HCs. The data was analyzed by moderated t-statistics and corrected by the Benjamini–Hochberg method. All statistical tests are two-sided. Source data are provided as a Source Data file.