基于肠道菌群调节PI3K/Akt和NF-κB信号通路与抑郁症的关联研究

Depression has become one of the most important diseases that endanger people's mental and physical health, and even life. It is extremely urgent to clarify its pathological mechanism so as to effectively reduce the high incidence of this disease. The Microbiota-Gut-Brain axis hypothesis has the impressively potential to fully describe the pathological mechanism of depression, and providing the feasibility for finding its important risk factors. This study selected intestinal flora (Microbiota-Gut-Brain axis key component part) as the breakthrough point, through several methods including 16S rRNA sequencing analysis, animal model constructing and intervention experiments to identify whether the intestinal flora can be the one needs to be pay more attention as the important risk factor of depression, and try to explore the related mechanisms of intestinal flora to depression by detecting the regulating ability of intestinal flora to PI3K/Akt and NF-κB signaling pathways. Intestinal dysbacteriosis with the characteristic of abnormally increasing number of bacteria with LPS components once occurred, its abilities of regulating inflammatory reaction and protecting intestinal mucosa barrier may significantly decrease. This will lead to an abnormal function of Microbiota-Gut-Brain axis, then increase the risk of depression. The purpose of this study is to find reliable evidences for maintaining a good intestinal flora status can effectively prevent depression from becoming a susceptible population and provide valuable scientific basis for effective prevention and treatment of depression.

抑郁症已经成为危害人类心身健康甚至生命的最主要疾病之一，明确其病理机制以有效降低该疾病的高发病率迫在眉睫。菌-肠-脑轴假说存在可全面阐述抑郁症病理机制的潜力，为寻找引发抑郁症的重要风险因素提供了可行性。本研究以肠道菌群（菌-肠-脑轴中的关键组成部分）为切入点，通过16SrRNA测序分析、构建动物模型及干预实验等方法鉴定肠道菌群失调是否可以作为需要被重视的引发抑郁症的重要风险因素，并通过检测肠道菌群对PI3K/Akt和NF-κB信号通路的调控能力，尝试阐明肠道菌群对抑郁症的相关作用机制，即以含LPS成分的细菌数量异常增加为特点的肠道菌群失调一旦发生，其对炎性反应的调控及对肠黏膜屏障的保护能力可能将显著降低，从而导致菌-肠-脑轴功能异常，随之抑郁产生的风险性上升。该研究意在为强调维持肠道菌群良好状态可有效避免成为抑郁症易感人群寻找可靠证据，也为抑郁症的有效防治策略提供有价值的科学依据。

抑郁症已经成为危害人类心身健康甚至生命的最主要疾病之一，明确其病理机制以有效降低该疾病的高发病率迫在眉睫。微生物群-肠-脑轴假说存在可全面阐述抑郁症病理机制的潜力，为寻找引发抑郁症的重要风险因素提供了可行性。本研究以肠道菌群（微生物群-肠-脑轴中的关键组成部分）为切入点，通过构建动物模型及NovaSeq 测序平台高通量16S rRNA 扩增子测序分析方法鉴定肠道菌群失调是否可以作为需要被重视的引发抑郁症的重要风险因素，通过白细胞介素酶联免疫检测了解到健康对照组、抑郁组和抗抑郁组动物模型免疫因子表达关联性， 通过液质联用（LC-MS/MS）技术进行了非靶向代谢组学研究。研究结果鉴定了肠道菌群失调是引发抑郁症的重要风险因素，发现了在动物模型抑郁及抗抑郁过程中存在差异性的肠道菌群结构以及相关代谢产物，在强调维持肠道菌群良好状态可有效避免成为抑郁症易感群体中寻找到可靠证据，以及发现群体存在来自于肠道菌群及其代谢产物的抗抑郁保护因子提供了有价值的科学依据。