基于肠道菌群/5-HT/ENS调控的番茄红素改善肠动力作用机制研究

随着生活节奏加快及饮食结构改变，肠动力紊乱等肠健康问题日益凸显。通过调整膳食组分及结构改善肠动力和应激变化的策略已成为食品营养学领域关注的热点。申请者研究发现食源性功能成分番茄红素可有效改善肠转运功能、调节肠道中与肠神经递质5-HT产生相关菌群的丰度，但目前肠道菌群与肠神经系统在番茄红素改善肠功能中的参与作用及关联机制尚不清楚。因此，本项目以肠道菌群及肠神经系统（ENS）为靶点，通过构建慢性压力动物模型，结合高通量测序、免疫荧光等检测技术，评价番茄红素对小鼠肠转运功能的改善作用；明确番茄红素对肠道菌群结构、肠黏膜下和肠肌间神经丛中5-HT蛋白表达的调节作用；并利用抗生素构建无菌小鼠模型，结合5-HT产生限速酶TPH1阻断剂干预，多角度阐明肠道菌群/5-HT/ENS在番茄红素调节肠动力中的作用与介导机制。研究预期为食源性功能组分调节肠稳态的精准营养干预提供新策略。

With the accelerated pace of life and the change of diet structure, intestinal health problems such as intestinal motility disorder have become increasingly prominent. It has become a research hotspot in the field of food nutrition to improve intestinal stress and motility by adjusting dietary components and structure. The applicant's previous research found that lycopene, a functional component derived from food, can effectively improve the intestinal transport function and regulate the abundance of intestinal microbiome related to the production of 5-HT. However, the role and mechanism of intestinal microbiome and enteric nervous system in the improvement of intestinal function by lycopene are still unclear. Therefore, the present project takes intestinal microbiome and enteric nervous system (ENS) as the research target, and utilizes chronic stress mice model combined with high-throughput sequencing, immunofluorescence and other technologies to detect intestinal transport function, reveal the changes of intestinal microbiome and analyze the expression of 5-HT response protein in intestinal submucosal and intestinal myenteric plexus, so as to clarify the improvement effect of lycopene on enteric nervous system abnormalities and intestinal motility disorders. In addition, TPH1 inhibitor and germ-free mice models are established to illustrate the effect and mediating mechanism of intestinal microbiome/5-HT/ENS in the regulation of intestinal motility by lycopene from multiple perspectives. Above all, the project is expected to provide a new strategy for precise nutritional intervention of functional food components in regulating intestinal homeostasis.