动脉粥样硬化（Atherosclerosis, AS）是心血管疾病的主要病理基础，慢性炎症是AS的主要病理特征。最近研究显示高脂饮食、肠道菌群及其代谢物引发的一系列炎症反应与AS形成有关，寻找合适的动物模型对AS疾病靶向菌群治疗策略和抗炎靶点的研究具有重要意义。小型猪是研究AS和肠道微生物的合适模型。我们前期研究发现高脂诱导AS西藏小型猪模型呈现慢性的系统性炎症，与人类AS的炎症病理极为类似，并初步发现该模型存在肠道菌群失调现象。我们推测高脂诱导AS西藏小型猪模型的慢性炎症与肠道菌群及其代谢产物有关。本项目用宏基因组学和代谢组学研究高脂诱导西藏小型猪AS进程中肠道菌群和代谢物的变化，关联分析并验证与AS炎症相关的肠道菌群、代谢物及其代谢通路，探讨高脂诱导AS西藏小型猪模型的慢性炎症机制，为在心血管代谢性疾病研究中的应用提供参考，为靶向调节肠道菌群和抗炎靶点药物的研究提供一个理想的动物模型。

Atherosclerosis (AS) is the main pathological basis of cardiovascular disease, of which the main pathological feature is chronic inflammation. Recent studies have shown that a series of systemic inflammation triggered by high-fat diet, gut microbiota and their metabolites is related to AS. Finding the right animal model is of great importance for the research of targeted microbiome therapy strategies and anti-inflammatory targets in AS diseases. The minipig is a suitable model for studying AS and gut microbes. Our previous study found that the high-fat diet induced AS Tibetan minipig model showed chronic systemic inflammation, which was extremely similar to the inflammatory pathology of human AS, and preliminarily found that the model had intestinal flora imbalance. Thus, we hypothesized that chronic inflammation of AS Tibetan minipig model induced by high-fat diet is associated with intestinal flora and their metabolites. This project uses metagenomics and metabolomics techniques to study the changes of intestinal flora and metabolites in the process of AS in high-fat diet induced Tibetan minipigs, followed by analyzing and verifying the relevance of intestinal flora and metabolites and their metabolic pathways associated with AS inflammation, and explore the inflammatory mechanism of high-fat diet induced AS Tibetan minipig model, providing references for the application in cardiovascular metabolic disease research, and supplying an ideal animal model for the study of targeted modulation of intestinal flora and anti-inflammatory target drugs.