肠道菌群可通过神经、内分泌、免疫等途径实现与大脑的交流，益生菌干预及其对肠道菌群的调节作用也成为目前实现中枢神经调节的新策略之一。然而，关于益生菌调节中枢神经活动的机制研究仍十分有限。申请人前期研究首次发现短双歧杆菌CCFM1025能够特异性地调节机体5-羟色氨酸（5-HTP）/5-羟色胺（5-HT）途径。本项目拟聚焦于该菌，研究其对肠道嗜铬细胞5-HTP合成的调控机制；通过宏基因组及代谢组学分析，阐明该菌介导的肠道菌群变化及对应代谢产物对肠道5-HTP水平的影响，以及肠源5-HTP参与脑内5-HT合成的转运及代谢动力学机制；通过比较基因组、代谢组等多组学手段，对该菌发挥功能的遗传学背景进行分析，以期发现短双歧杆菌发挥中枢神经调节功能的规律及物质基础。本项目拟建立益生菌参与肠-脑对话的5-HTP/5-HT途径，深入解析益生菌参与中枢神经系统调节的具体机制，具有重要的理论意义和应用价值。

Gut microbiota communicates with the brain through nerve, endocrine, and immune system. Therefore, probiotics intervention and its regulation on gut microbiota has become one of the new strategies for achieving regulation of neurological function. However, the underlying mechanisms are still unclear. Our preliminary study discovered for the first time that Bifidobacterium breve CCFM1025 could specifically regulate the biosynthesis of 5-hydroxytryptophan (5-HTP)/5-hydroxytryptamine (5-HT). This project aims to study the effect of CCFM1025 on 5-HTP synthesis in the intestinal enterochromaffin cells. Through meta-genomics and metabolomics analysis of gut microbiota, to elucidate the key gut flora changes and corresponding metabolites which affect the intestinal 5-HTP levels. Additionally, the transport and metabolic dynamics of 5-HTP derived from the gut to brain will also be investigated. Finally, we will clarify the genetic and material feature of CCFM1025 through comparative genomics, proteomics and metabolomics analysis. We tend to establish a 5-HTP/5-HT dependent pathway for probiotics to participate in the gut-brain interaction. This study has significant theoretical and application value, which can provide more new theoretical basis for development of new functional strains.