School of Pharmacy, Naval Medical University, Shanghai 200433, China.
School of Pharmacy, Naval Medical University, Shanghai 200433, China; School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
J Affect Disord. 2024 Jan 1;344:563-576. doi: 10.1016/j.jad.2023.10.104. Epub 2023 Oct 18.
Depression is a chronic, relapsing mental illness, often accompanied by loss of appetite, increased fatigue, insomnia and poor concentration. Here, we performed serum and urine metabolomics and fecal 16S rDNA sequencing studies on 57 unmedicated patients with major depressive disorder (MDD) and 57 healthy controls to characterize the metabolic and flora profile of MDD patients. We observed significant differences in serum and urinary metabolome between MDD patients and healthy individuals. Specifically, glycerophospholipid metabolism, primary bile acid biosynthesis and linoleic acid metabolism were significantly disordered in serum, and aminoacyl-tRNA biosynthesis, arginine biosynthesis, purine metabolism, phenylalanine metabolism, alanine, aspartate and glutamate metabolism, and pyrimidine metabolism were significantly impaired in urine. On this basis, we identified four potential diagnostic biomarkers for carnitine and four fatty acid classes in serum and urine, respectively. In addition, we observed significant disturbances of the gut microbiota in MDD patients. Spearman correlation analysis showed that imbalances in the gut microbiota were associated with metabolic disturbances, suggesting an important role of the gut microbiota in the pathogenesis of MDD. Our study provides a theoretical basis for further understanding of the pathogenesis of depression and for future clinical diagnosis and screening, as well as a basis for targeting the gut flora to optimize its structure for the prevention and treatment of depression.
抑郁症是一种慢性、复发性精神疾病，常伴有食欲不振、疲劳增加、失眠和注意力不集中。在这里，我们对 57 名未经药物治疗的重度抑郁症（MDD）患者和 57 名健康对照者进行了血清和尿液代谢组学以及粪便 16S rDNA 测序研究，以描述 MDD 患者的代谢和菌群特征。我们观察到 MDD 患者与健康个体的血清和尿液代谢组之间存在显著差异。具体而言，甘油磷脂代谢、初级胆汁酸生物合成和亚油酸代谢在血清中明显失调，而氨基酸酰基-tRNA 合成、精氨酸生物合成、嘌呤代谢、苯丙氨酸代谢、丙氨酸、天冬氨酸和谷氨酸代谢以及嘧啶代谢在尿液中明显受损。在此基础上，我们分别在血清和尿液中鉴定出了四个潜在的诊断生物标志物，即肉碱和四种脂肪酸类。此外，我们观察到 MDD 患者的肠道微生物群存在显著紊乱。Spearman 相关分析显示，肠道微生物群的失衡与代谢紊乱有关，这表明肠道微生物群在 MDD 的发病机制中起着重要作用。我们的研究为进一步了解抑郁症的发病机制以及未来的临床诊断和筛查提供了理论依据，并为靶向肠道菌群优化其结构以预防和治疗抑郁症提供了依据。
