基于宏基因组学的中医气虚质代谢紊乱的机制研究

The formation of the constitution has become one of the focuses on the field of medicine. However, its mechanism has not yet been clarified. Our previous study found that the people in qi-deficiency constitution of Traditional Chinese Medicine have metabolic disorders. The intestinal flora disorder may result in some of the metabolic disease. By means of the metabonomics and microbiomics methods, we will get into the influence and mechanism how the qi-deficiency constitution affects the disorder of the body. Firstly, we will carry out a survey on the outward manifestation and of the selected people-- the qi-deficiency group, and gentle constitution group, as well as their feces metabonomics and microbiomics by means of NMR, HPLC/MS, GC-MS, ERIC-PCR. Secondly, we will establish a database of metabonomics and microbiomics differences metabolic map. We will analyze the inner relationship among the clinical phenotype, metabonomics and microbiomics by ways of bioinformatics method. We will also perfuse the fecal microbes of the qi-deficiency and gentle constitution into the sterile mouse intestines, to find the same point of the plasma metabolomics between human and the mice. Through the above methods, we can throw light on the mechanism how the qi-deficiency constitution affects the disorder of the body. It is very useful not only in preventing disease, but also in promoting the development of TCM constitution.

体质形成的原因已成为目前医学界研究的热点之一，然而其机制至今尚未阐明。我们前期研究发现中医气虚质的人存在明显的代谢紊乱。目前研究发现，肠道菌群紊乱是多种代谢性疾病的重要原因之一，因此，我们推测肠道菌群紊乱是引起气虚质代谢紊乱的原因之一。本项目拟应用宏基因组学结合代谢组学方法，对健康人气虚质、平和质人群粪便进行代谢组学、肠道微生物研究，对气虚质人群的肠道菌群结构和组成变化与其代谢产物的代谢谱进行分析，同时将气虚质、平和质人群的粪便微生物灌注于无菌鼠肠中，对比人类与无菌鼠血浆代谢组学，以探讨气虚质代谢紊乱的可能原因。这不仅对改善体质、防治疾病有重要意义，还将促进中医体质学说的发展。

体质形成的原因已成为目前医学界研究的热点之一，然而其机制至今尚未阐明。我们前期研究发现中医气虚质的人存在明显的代谢紊乱。目前研究发现，肠道菌群紊乱是多种代谢性疾病的重要原因之一，因此，我们推测肠道菌群紊乱是引起气虚质代谢紊乱的原因之一。本项目将肠道微生物与代谢组学结合，对健康人气虚质、平和质人群粪便进行代谢组学、肠道微生物研究发现:①气虚体质肠道菌群构成显著区别于平和体质。气虚体质有益菌与具有抗炎作用的菌群丰度下降；气虚体质菌群多样性小于平和质。具有促炎作用的菌群丰度上升。②气虚体质人群代谢通路偏向于氨基糖和核苷酸糖代谢、其他离子耦合转运蛋白、丙氨酸-天冬氨酸-谷氨酸的代谢、RNA 降解方面。气虚体质和平和体质两组尿液代谢产物具有显著差异。气虚体质中升高的代谢产物影响半胱氨酸和蛋氨酸代谢、酪氨酸代谢、柠檬酸循环、色氨酸代谢、乙醛酸和二羧酸代谢、苯丙氨酸代谢、嘧啶代谢、嘌呤代谢、缬氨酸，亮氨酸和异亮氨酸的生物合成等代谢通路。③应用补中益气丸干预气虚体质志愿者发现:补中益气丸的干预提高了气虚体质人群菌群的菌群多样性，可使气虚体质的菌群向平和质的菌群转化。补中益气丸干预前后尿液代谢产物具有显著差异。④将气虚质、平和质人群的粪便灌注于抗生素清除鼠的胃中，对比两组小鼠血浆代谢组学，发现两组间的代谢产物有明显差异。这些代谢产物影响脂肪酸代谢、三羧酸循环、鸟氨酸循环、氨基酸代谢、丙酮酸代谢、糖异生、嘌呤嘧啶代谢、氨回收、甘氨酸和丝氨酸代谢、神经递质传导、精氨酸和脯氨酸代谢、亮氨酸和异亮氨酸的生物合成、烟酸和烟酰胺代谢等。