乳酸片球菌CCFM6432通过缓解大脑炎症改善小鼠抑郁行为  

Pediococcus acidilactici CCFM6432 improves depressive behavior in mice by alleviating brain inflammation

作　　者：杨红宇 蒋家豪 裴雨轩 钱鑫 田培郡 王刚[1] 赵建新[1] YANG Hongyu;JIANG Jiahao;PEI Yuxuan;QIAN Xin;TIAN Peijun;WANG Gang;ZHAO Jianxin(School of Food Science and Technology,Jiangnan University,Wuxi 214122,China)

机构地区：[1]江南大学食品学院,江苏无锡214122

出　　处：《食品与发酵工业》2024年第19期25-32,共8页Food and Fermentation Industries

基　　金：国家自然科学基金青年项目(32201988)。

摘　　要：乳酸片球菌(Pediococcus acidilactici)是一类高产乳酸的益生菌,该文旨在探究乳酸片球菌CCFM6432对小鼠抑郁症状的缓解作用及其作用机制。该研究通过为期4周的慢性不可预知温和刺激建立抑郁小鼠模型,并给予小鼠益生菌(乳酸片球菌CCFM6432和对照菌株FXJKS25M4)干预治疗。肠道菌群和代谢物分析结果显示,相比于模型组和对照组,CCFM6432干预后能显著调节肠道代谢物乳酸、鸟嘌呤和腺嘌呤等的含量,降低肠道致病菌的丰度,并提高了短链脂肪酸合成菌属毛螺菌科(Lachnospiraceae)的丰度,有助于恢复肠道屏障损伤,逆转血清中脂多糖(lipopolysaccharide,LPS)异常升高。此外,CCFM6432还能下调脑部TLR4/NF-kB信号通路的受体蛋白和促炎因子的异常表达,从而抑制海马中小胶质细胞的过度活化。该研究揭示了CCFM6432通过调节特定肠道代谢物来抑制肠道致病菌的生长,从而缓解神经炎症导致的抑郁症状,并为抑郁症治疗方法以及肠-脑轴信号通路探索提供新的见解。Pediococcus acidilactici is a group of probiotics known for its high lactate production.This study aims to investigate the alleviation of depressive symptoms in mice by P.acidilactici CCFM6432 and its underlying mechanisms.A Chronic Unpredictable Mild Stress(CUMS)model in mice was established for 4 weeks,followed by probiotic interventions with Lactobacillus strains(CCFM6432 and control strain FXJKS25M4).Results from the analysis of gut microbiota and metabolites revealed that,compared to both the model and control groups,CCFM6432 intervention significantly regulated the levels of gut metabolites such as lactate,uracil,and adenine.This intervention reduced the abundance of pathogenic gut bacteria and increased the abundance of Lachnospiraceae,a family associated with short-chain fatty acid synthesis,thereby assisting in the restoration of intestinal barrier integrity and the normalization of elevated lipopolysaccharide(LPS)levels in the serum.Additionally,CCFM6432 downregulated the expression of receptor proteins and pro-inflammatory factors involved in the TLR4/NF-kB signaling pathway in the brain.This inhibition contributed to the suppression of excessive microglial cell activation in the hippocampus.This study elucidates how CCFM6432 alleviates depressive symptoms by regulating specific gut metabolites to inhibit the growth of pathogenic gut bacteria,shedding light on novel insights for the treatment of depression and the exploration of the gut-brain axis signaling pathways.

关 键 词：乳酸片球菌 乳酸 抑郁 脂多糖 炎症 小胶质细胞 

分 类 号：TS201.4[轻工技术与工程—食品科学] TS201.3[轻工技术与工程—食品科学与工程] R749.4[医药卫生—神经病学与精神病学]