膳食丝氨酸基于“营养-肠道菌群-肠道黏膜屏障”轴抵御炎症性肠病的作用机制

我们发现膳食丝氨酸可通过限制黏液降解菌的扩繁，维持肠粘膜屏障功能，抵御炎症性肠病，但其作用机制尚不清楚。本项目拟建立黏液降解菌定植的无菌小鼠结肠炎模型，利用病理学、qPCR、葡聚糖示踪等技术，分析缺乏膳食丝氨酸诱发的黏液降解菌对黏液屏障造成的损伤，探讨膳食丝氨酸调节黏液降解菌保护黏液屏障的直接作用机制；利用细菌16S rRNA和RNA-Seq测序技术，研究缺乏膳食丝氨酸对丝氨酸利用和黏液降解有关的肠道菌群组成和功能的影响，探讨膳食丝氨酸调节肠道菌群对维持肠黏液屏障完整性的影响；建立黏液降解菌和丝氨酸利用菌共定植的无菌小鼠结肠炎模型，利用病理学、qPCR、葡聚糖示踪等技术，研究缺乏膳食丝氨酸诱发的黏液降解菌和丝氨酸利用菌之间的营养互作，探讨膳食丝氨酸调节肠道菌群互作保护肠粘膜屏障的间接作用机制。本项目将阐明膳食丝氨酸-肠道菌群-肠道黏液屏障之间的复杂关系，为开发新的IBD营养疗法提供科学依据

We found that dietary serine can maintain the integrity of the intestinal mucus barrier and resist inflammatory bowel disease by limiting the proliferation of mucus-degradation bacteria, but the mechanism of dietary serine is still unclear. This project intends to establish a mucus-degradation bacteria colonized gnotobiotic mice model in colitis, using pathology, qPCR, and dextran tracer to analyze the dietary serine-induced mucus barrier damage caused by mucus-degradation bacteria and explore the direct mechanism of dietary serine in the regulation of mucus-degradation bacteria to protect the mucus barrier; Using bacterial 16S rRNA and RNA-Seq sequencing technology to study the effect of dietary serine deficiency on the composition and function of intestinal flora related to serine utilization and mucolysis, and analyze the effects of dietary serine regulation of intestinal flora on the maintenance the integrity of intestinal mucus barrier. Establish mucus-degradation bacteria and serine-utilizing bacteria co-colonized gnotobiotic mice model in colitis, using pathology, qPCR, and dextran tracer to analyze the lack of dietary serine induced nutritional interactions between mucus-degradation bacteria and serine-utilizing bacteria, and to explore the indirect mechanism of dietary serine regulating intestinal flora interactions to protect the intestinal mucus barrier. This project will clarify the complex relationship between dietary serine-intestinal flora-intestinal mucus barrier, provide a strong scientific basis for the development of new nutritional treatment methods for IBD.