目的:通过比较首发未治疗的抑郁障碍(major depressive disorder，MDD)患者和健康对照血清糖脂代谢指标、血浆和粪便中胰高血糖素样肽-1(glucagon-like peptide-1，GLP-1)水平及肠道特定菌群(乳酸杆菌、双歧杆菌)含量，探讨MDD的发病机制。方法:选取2020年1月1日至2021年3月30日住院治疗的MDD患者和同一时期体检正常的健康志愿者各80例。分别采集MDD患者和健康对照的血液、粪便样本，采用全自动生化仪检测血清糖脂代谢相关指标，使用ELISA方法检测血浆和粪便中GLP-1水平，使用实时荧光定量PCR检测肠道乳酸杆菌、双歧杆菌相对含量，分析组间糖脂代谢指标、GLP-1水平及肠道乳酸杆菌、双歧杆菌相对含量差异。采用SPSS 22.0软件进行统计分析，组间比较采用独立样本n t检验、方差分析，相关性分析采用Pearson相关分析。n 结果:MDD组TC、HDL、LDL水平低于健康对照组[(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; n t＝5.559，2.371，4.695，均n P<0.05]。MDD组血浆、粪便GLP-1水平均低于对照组[血浆：(0.81±0.22)pmol/mL，(1.05±0.26)pmol/mL，n t＝4.509，n P<0.01；粪便：(2.23±0.46)pmol/mL ，(2.47±0.37)pmol/mL，n t＝2.533，n P<0.05]。MDD组粪便中乳酸杆菌(2.56±1.59，3.51±2.21)、双歧杆菌(2.24±1.89 ，3.17±2.08)相对含量低于健康对照组(n t＝2.218，2.082，均n P<0.05)。MDD组血浆GLP-1水平与FPG、TG、疾病严重程度呈负相关(n r＝-0.281、-0.221、-0.437，n P<0.05)，对照组血浆GLP-1水平与FPG呈负相关(n r＝-0.580，n P<0.01)；MDD组粪便GLP-1水平与疾病严重程度呈负相关(n r＝-0.298，n P<0.01)，健康对照组粪便GLP-1水平与肠道乳酸杆菌、双歧杆菌呈正相关(n r＝0.685、0.428，n P<0.01)。n 结论:MDD患者存在糖脂代谢异常、GLP-1水平降低及肠道乳酸杆菌、双歧杆菌相对含量下降，肠道菌群的改变影响了GLP-1水平，GLP-1可通过和肠道及中枢神经系统的特异性受体结合对MDD患者糖脂代谢和抑郁症状产生作用。“,”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 (n Lactobacillus, n Bifidobacterium) between patients with MDD who were diagnosed for the first time and healthy controls.n 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 n Lactobacillus and n 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 n Lactobacillus and n Bifidobacterium in feces were analyzed. SPSS 22.0 software was used for statistical analysis. Independent sample n t-test and analysis of variance were used for inter group comparison, and Pearson correlation analysis was used for correlation analysis.n 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; n t=5.559, 2.371, 4.695, all n 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 ,n t=4.509, n P<0.01; feces: (2.23±0.46)pmol/mL , (2.47±0.37)pmol/mL,n t=2.533, n P<0.05). Compared with the control group, the relative contents ofn Lactobacillus(2.56±1.59, 3.51±2.21) and n Bifidobacterium(2.24±1.89 , 3.17±2.08) in the MDD group decreased (n t=2.218, 2.082, both n P<0.05). The level of plasma GLP-1 in the MDD group was negatively correlated with FPG, TG, and disease severity (n r=-0.281, -0.221, -0.437, n P<0.05). The level of plasma GLP-1 in the control group was negatively correlated with FPG (n r=-0.580, n P<0.01). The fecal GLP-1 level of the MDD group was negatively correlated with the severity of the disease (n r=-0.298, n P<0.01), and the fecal GLP-1 level of the control group was positively correlated with fecaln Lactobacillus and n Bifidobacterium (n r=0.685, 0.428, n P<0.01).n Conclusion:MDD patients have abnormal glucose and lipid metabolism, decreased GLP-1 level and decreased relative content of intestinal n Lactobacillus and n 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.n