Objective:To explore the pathogenesis of major depressive disorder(MDD) by comparing the serum glucose and lipid metabolism indicators, levels of glucagon-like peptide-1(GLP-1) in plasma and feces, and the content of specific intestinal flora ( Lactobacillus, Bifidobacterium) between patients with MDD who were diagnosed for the first time and healthy controls. Methods:Totally 80 MDD patients hospitalized from January 1, 2020 to March 30, 2021 and 80 healthy volunteers with normal physical examination in the same period were selected. Blood and fecal samples of patients with MDD and healthy controls were collected respectively. The indicators of serum glucose and lipid metabolism were detected by automatic biochemical analyzer, the concentrations of GLP-1 in plasma and feces were detected by ELISA, and the relative contents of Lactobacillus and Bifidobacterium in feces were detected by real-time PCR. The differences between two groups of glucose and lipid metabolism indicators, GLP-1 levels and the relative contents of Lactobacillus and Bifidobacterium in feces were analyzed. SPSS 22.0 software was used for statistical analysis. Independent sample t-test and analysis of variance were used for inter group comparison, and Pearson correlation analysis was used for correlation analysis. Results:Compared with the control group, the levels of serum TC, HDL, and LDL in the MDD group decreased ((3.99±0.85)mmol/L , (4.78±0.86)mmol/L; (1.18±0.29)mmol/L, (1.30±0.28)mmol/L; (2.64±0.70)mmol/L, (3.19±0.69)mmol/L; t=5.559, 2.371, 4.695, all P<0.05). The plasma and fecal GLP-1 levels of the MDD group were lower than those of the control group (plasma: (0.81±0.22)pmol/mL, (1.05±0.26)pmol/mL , t=4.509, P<0.01; feces: (2.23±0.46)pmol/mL , (2.47±0.37)pmol/mL, t=2.533, P<0.05). Compared with the control group, the relative contents of Lactobacillus(2.56±1.59, 3.51±2.21) and Bifidobacterium(2.24±1.89 , 3.17±2.08) in the MDD group decreased ( t=2.218, 2.082, both P<0.05). The level of plasma GLP-1 in the MDD group was negatively correlated with FPG, TG, and disease severity ( r=-0.281, -0.221, -0.437, P<0.05). The level of plasma GLP-1 in the control group was negatively correlated with FPG ( r=-0.580, P<0.01). The fecal GLP-1 level of the MDD group was negatively correlated with the severity of the disease ( r=-0.298, P<0.01), and the fecal GLP-1 level of the control group was positively correlated with fecal Lactobacillus and Bifidobacterium ( r=0.685, 0.428, P<0.01). Conclusion:MDD patients have abnormal glucose and lipid metabolism, decreased GLP-1 level and decreased relative content of intestinal Lactobacillus and Bifidobacterium. Changes in intestinal flora affect GLP-1 levels. GLP-1 can affect glucose and lipid metabolism and depressive symptoms in patients with MDD by binding to specific receptors in intestinal tract and central nervous system.