“肠道菌群-microRNAs轴”介导藻蓝色素干预糖代谢的分子机制研究

随着我国居民生活质量的不断提高，“营养过剩”引起的糖代谢失调已成为威胁我国人民健康的重要问题之一。藻蓝色素是一种源于海洋藻类的天然食品活性因子，有研究表明藻蓝色素能够通过调节肠道菌群和microRNA的表达改善机体的糖代谢稳态，但它们之间的具体互作机制尚不清楚。本项目以“肠道菌群-miRNAs轴”互作体系为研究模型，借助miRNA转录组、肠道菌群多样性以及非靶向代谢组的多组学联合分析技术为研究手段，考察糖代谢调控过程中miRNA、肠道菌群及其代谢物的变化规律；通过靶点预测和突变技术探究miRNA的靶基因；利用粪菌移植和体内转染技术解析肠道菌群与miRNA的互作关系；最终结合Metacore分析软件解析藻蓝色素改善糖代谢的分子机制。研究成果将从机体水平阐明“肠道菌群-miRNAs轴”参与调控糖代谢的途径，为我国居民“营养膳食”改善糖代谢稳态提供指导依据，具有重要的理论研究意义和实际应用价值。

With the continuous improvement of nutrition intake level and quality of life, the imbalance of glycometabolism caused by “overnutrition” has become one of the important problems threatening our health. Phycocyanin is a type of food active factor which derived from marine algae. Studies have shown that phycocyanin can improve the body’s glycometabolism homeostasis through regulating gut microbiota and microRNA expression, but the specific regulatory mechanism between them is still unclear. In this project, the “gut microbiota-miRNA axis” interaction system was used as the research model, and the multi-omics combined analysis technology including miRNA transcriptome, gut microbiota diversity and non-targeted metabolome was employed to investigate the change patterns of miRNA, gut microbiota and their metabolites in regulating glycometabolism. The target genes of miRNA were investigated by target mutation technique. Fecal microbiota transplantation and in vivo transfection techniques were used to analyze the interaction relationship between gut microbiota and miRNA. Finally, the molecular mechanism of phycocytanin-regulated improving glycometabolism process was analyzed by Metacore analysis software. The research results will elucidate the regulatory pathway of “gut microbiota-miRNA axis”-invloved regulation process of glycometabolism, and provide guidance for Chinese residents to improve the homeostasis of glycometabolism through “nutritious diet”, which has important theoretical significance and practical application value.