高热能膳食模式下Muc2黏蛋白介导的肠道菌群与宿主生物节律的交互机制研究

高热能膳食摄入过多会导致机体营养物质代谢失衡及肥胖等继发性健康问题。最新研究表明，肠道菌群可经由宿主生物钟基因调控高脂膳食下机体的脂肪酸氧化分解过程，而肠道菌群与宿主生物节律交互作用的分子机制尚不清楚。黏液糖蛋白2（Muc2）作为肠上皮黏液层的主要成分，在宿主与肠道菌群的信号交互中起重要作用。申请者前期研究发现Muc2具有节律性表达的特征，并且在高脂膳食的作用下受到显著抑制。本项目拟建立高脂膳食模型，以肠道菌群节律、生物钟基因、Muc2分子信号为研究靶点，运用多学科交叉技术手段，研究高脂膳食对肠道菌群特征代谢物、肠道Bmal1生物钟基因及Muc2分子节律震荡的影响，探讨肠道菌群节律、Bmal1生物钟基因对Muc2分子信号的调控作用，阐明高脂膳食模式下Muc2分子信号在肠道菌群节律与生物钟基因交互作用中的参与机制。研究结果预期为揭示高热能膳食健康问题机制及其营养学干预研究提供理论依据。

High calorie diet will cause disorder of nutrient metabolism, obesity, and other secondary health problems. Recent studies have found that the gut microbiomepotently regulates the oxidation and decomposition of fatty acids via host circadian rhythm. While the molecular mechanism of the interaction between the gut microbiome and host circadian rhythm system is still unclear. Muc2, which is the main component of the mucous layer in intestinal epithelium, plays a critical role in the interaction between host and gut microbiome. Our previous studies have found that Muc2 mucin exhibited drastic fluctuations in a 24-h period, and high-fat diet dampened the cyclical fluctuation of Muc2. With the gut microbiome circadian, clock gene and Muc2 molecular signal as the target, the project intends to adapt multidisciplinary cross-disciplinary techniques to clarify the influence of high-fat diet on gut microbiome characteristic metabolites, intestinal Bmal1 biological clock gene and the Muc2 molecular rhythm oscillation. This project is also aimed at the effects of gut microbiome rhythm and Bmal1 clock gene on Muc2 molecular signals. Furthermore, the project attempts to reveal the involvement of Muc2 molecular signals in the interaction between gut microbiome rhythm and clock genes. This research is expected to provide a new strategy and theoretical basis for the disorder of glucose and lipid metabolism caused by excessive nutrition.