NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; School of Basic Medical Sciences, Department of Pathology, Chongqing Medical University, Chongqing 400016, China.
NHC Key Laboratory of Diagnosis and Treatment on Brain Functional Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Gene. 2024 Nov 15;927:148633. doi: 10.1016/j.gene.2024.148633. Epub 2024 Jun 3.
Depression, which is a disease of heterogeneous etiology, is characterized by high disability and mortality rates. Gut microbiota are associated with the development of depression. To further explore any differences in the mechanisms of depression induced by gut microbiota and traditional stresses, as well as facilitate the development of microbiota-based interventions, a fecal microbiota transplantation (FMT) depression model was made. This was achieved by transplanting feces from major depressive disorder (MDD) patients into germ-free mice. Second, the mechanisms of the depression induced by gut microbiota were analyzed in comparison with those of the depression caused by different forms of stress. It turned out that mice exhibited depressive-like behavior after FMT. Then, PCR array analysis was performed on the hippocampus of the depressed mice to identify differentially expressed genes (DEGs). The KEGG analysis revealed that the pathways of depression induced by gut microbes are closely associated with immuno-inflammation. To determine the pathogenic pathways of physiological stress and psychological stress-induced depression, raw data was extracted from several databases and KEGG analysis was performed. The results from the analysis revealed that the mechanisms of depression induced by physiological and psychological stress are closely related to the regulation of neurotransmitters and energy metabolism. Interestingly, the immunoinflammatory response was distinct across different etiologies that induced depression. The findings showed that gut microbiota dysbiosis-induced depression was mainly associated with adaptive immunity, while physiological stress-induced depression was more linked to innate immunity. This study compared the pathogenesis of depression caused by gut microbiota dysbiosis, and physiological and psychological stress. We explored new intervention methods for depression and laid the foundation for precise treatment.
抑郁症是一种病因复杂的疾病，其特点是高残疾率和死亡率。肠道微生物群与抑郁症的发展有关。为了进一步探讨肠道微生物群和传统应激引起的抑郁症机制的差异，并促进基于微生物群的干预措施的发展，建立了粪便微生物群移植（FMT）抑郁症模型。这是通过将重度抑郁症（MDD）患者的粪便移植到无菌小鼠中来实现的。其次，分析了肠道微生物群引起的抑郁症的机制，并与不同形式应激引起的抑郁症的机制进行了比较。结果表明，FMT 后小鼠表现出抑郁样行为。然后，对抑郁小鼠的海马体进行 PCR 阵列分析，以鉴定差异表达基因（DEGs）。KEGG 分析表明，肠道微生物群引起的抑郁症的途径与免疫炎症密切相关。为了确定生理应激和心理应激引起的抑郁症的致病途径，从几个数据库中提取原始数据并进行 KEGG 分析。分析结果表明，生理和心理应激引起的抑郁症的机制与神经递质和能量代谢的调节密切相关。有趣的是，不同病因引起的抑郁症的免疫炎症反应明显不同。研究结果表明，肠道微生物群失调引起的抑郁症主要与适应性免疫有关，而生理应激引起的抑郁症与先天免疫的关系更为密切。本研究比较了肠道微生物群失调、生理和心理应激引起的抑郁症的发病机制。我们探讨了抑郁症的新干预方法，并为精准治疗奠定了基础。
