抑郁症作为一种神经心理疾病，具有高发病率和高死亡率，肠腔菌群-肠道-大脑轴与行为、认知密切相关。研究发现派伊尔结是菌群与免疫细胞发生接触，并实现肠粘膜免疫应答的关键部位；我们前期发现抑郁样肥胖小鼠派伊尔结内菌群结构紊乱。然而，派伊尔结内生菌群能否通过调节肠粘膜免疫而影响抑郁尚缺乏全局性和机理性的认识。本项目拟以慢性社会挫败应激导致的抑郁样小鼠为模型，通过靶向派伊尔结免疫应答的抗炎性内生Lactobacillus reuteri L3对其干预，借助Illumina高通量检测、流式细胞术、代谢组学、RT-PCR、免疫印迹等技术系统阐明派伊尔结内生菌群通过诱导粘膜免疫应答，导致肠通透性改变，引起神经炎症，继而通过吲哚胺-2,3-双加氧酶等表达影响神经递质的合成，以调节抑郁行为。研究结果将为高效微生态制剂的研究提供新思路，并对临床合理开展抑郁症的预防及治疗提供重要理论依据。

Depression is one major causes of morbidity and mortality and is associated with impaired health-related quality of life. The microbiota–gut–brain axis is associated with alterations in behaviour and cognition. Peyer’s patches (PP) is entry site for bacteria. PP contain immunocompetent cells and is thought to be the key inductive sites for mucosal immune responses. Our previous study observed that the changes in the composition of indigenous opportunistic bacteria in the PP were associated with obesity. However, the role of PP indigenous opportunistic bacteria in neuronal immune system and depression has received little attention to date. In this study, we will use an depression animal model induced by chronic social defeat stress (CSDS) to prove the hypothesis that the changes in the composition of indigenous opportunistic bacteria in the PP are associated with depression. Lactobacillus reuteri L3 isolated from the PP is used to modulate mucosal immune responses. Illumina high-throughput sequencing is used to describe gut flora structures, while Flow cytometry is used to analysis the composition of T lymphocyte in PP. RT-PCR and Western blot are also used to estimate the expression of gene and protein, respectively. The data predict novel pathways that might underlie microbiota-mediated effects on brain and behavior, thus presenting targets for investigations into mechanisms and potential therapy.