肠道菌群与冠心病发展过程中证候虚实差异的关联研究

Coronary heart disease (angina pectoris-myocardial infarction-heart failure) is a succession of extremely high incidence of progressive diseases, and it is urgent to find new targets of diagnosis and treatment that accord with the characteristics of sequential progression. Recent studies have shown that characteristics of intestinal flora complying with environmental changes are closely related to the development of coronary heart disease and TCM syndromes, but there is no study on characteristics of sequential change of intestinal microflora in coronary heart disease based on the combination of disease and syndrome. In view of the similar characteristics of intestinal flora and traditional Chinese medicine, 90 patients with deficiency of qi and yin or phlegm and blood stasis syndrome in CHD (angina pectoris or myocardial infarction or heart failure), 30 healthy controls, were selected in this project. By using the method of association study between metagenomics and metabolomics, and high-throughput sequencing technology to study the association characteristics of intestinal flora in the process of sequential development of CHD (angina pectoris or myocardial infarction or heart failure), to search for specific flora, gene and metabolic pathway with sequential characteristics, to screen the specific biomarkers of Qi and Yin deficiency syndrome, phlegm and blood stasis syndrome, to reveal the endogenous mechanism of sequential development of CHD, interpret the connotation of "different diseases with same syndrome" and “different syndromes in same disease”, and to enrich the objective basis of microcosmic differentiation in TCM. This project may provide new strategies and methods for the prevention and treatment of coronary heart disease, which has important theoretical significance and clinical application prospect.

冠心病心绞痛-心梗-心衰是一类极高发接续性疾病，亟需发掘符合其序贯性进展特征的新诊疗靶点。研究证明，肠道菌群顺应环境变化与冠心病发生发展及中医证候均关系密切，但尚未见基于病证结合的冠心病接续发展菌群特征研究。鉴于肠道菌群与中医相似的整体、系统、恒动特征，本项目拟在前期基础上，选取冠心病心绞痛-心梗-心衰气阴两虚证与痰瘀互结证患者共90例，健康对照30例，运用宏基因组学与代谢组学关联比较分析方法，利用高通量测序技术，从微生物群落物种、功能等角度，研究心绞痛-心梗-心衰接续进程肠道菌群与代谢标志物的关联特征，寻找具有序贯性特征的特异菌群、基因和代谢通路，筛选气阴两虚证、痰瘀互结证的特异性生物标志物，揭示冠心病接续发展的内源机制，诠释“异病同证”、“同病异证”的内涵，丰富中医微观辨证的客观依据。本项目有可能为冠心病的预防和诊疗提供新的策略和方法，具有重要的理论意义和应用前景。

冠心病心绞痛-心梗-心衰是一类极高发接续性疾病，亟需发掘符合其序贯性进展特征的新诊疗靶点。研究证明，肠道菌群顺应环境变化与冠心病发生发展及中医证候均关系密切，但尚未见基于病证结合的冠心病接续发展菌群特征研究。鉴于肠道菌群与中医相似的整体、系统、恒动特征，本项目拟在前期基础上，对120受试者进行了多组学联合分析均（宏基因测序和代谢组学），我们发现在冠心病发展过程中及虚实证候间肠道菌群和代谢物的组成不同程度的发生了变化，结果显示确定了32种与冠心病心绞痛-心梗-心衰续惯性发展呈正、负相关的代谢物模块。续惯性发展不同阶段特征性富集的细菌共丰度族包括乳杆菌、肠杆菌属等，这些细菌可能参与甘露醇、胆汁酸、氧化三甲胺等代谢途径，表明冠心病心绞痛-心梗-心衰续贯发展存在代谢紊乱、肠道菌群改变可能与其密切相关。同时发现冠心病心绞痛-心梗—心衰虚实证候间患者肠道菌群-TMA-TMAO 代谢紊乱，糖代谢紊乱、氨基酸代谢紊乱，脂质代谢紊乱，能量代谢紊乱等异常机制彼此呈正负关联。确定了包括丝氨酸、肌酸酐、烟酰胺等11种冠心病续惯性发展过程中虚实证候间呈正、负相关的代谢物模块，发现气阴两虚证、痰瘀互结证间厚壁菌门、阿克曼氏菌、乳杆菌、梭菌属、肠球菌等菌属可能作为提示虚实证候差异的特征性菌群。肠道菌群与代谢产物与冠心病心绞痛-心梗—心衰接续发展过程中的虚实证候差异关系密切，可能成为证候诊断的生物标志物。