动物模型移植人源肠道菌群在中医药防治糖脂代谢病中的关键技术和挑战

Key Technology and Challenges in The Transplantation of Human Fecal Microflora into Animal Models for the Investigation of Therapeutic Effect of Chinese Medicine on Glucolipid Metabolic Disorders

糖脂代谢病是影响和危害全球公共健康的一类重大疾病。近年来,越来越多的证据指向糖脂代谢病和肠道菌群结构和功能改变密切相关。但是,临床研究很难在人群进行干预试验揭示肠道菌群改变与疾病核心机理的因果关系。因此,动物模型移植人源肠道菌群成为揭示中医药等干预策略或临床特征与肠道菌群改变因果关系的关键研究策略之一。动物模型移植人源肠道菌群研究方法主要包括4个主要步骤:1)采集观察组和对照人群的的粪便,进行移植菌液制备; 2)广谱抗生素诱导的条件性无菌小鼠诱导; 3)运用整体菌群或经宏基因组学分析鉴定出的特异性菌属,移植到条件性无菌小鼠后,进行代谢性疾病动物模型诱导; 4)比较分别接受干预组和对照组人源肠道菌群移植小鼠的糖脂代谢表型。作为肠道菌群研究领域的前沿方法之一,动物模型移植人源肠道菌群为中医药防治糖脂代谢病提供了新思路和线索。

Glucolipid metabolic Disease (GLMD) is one of leading chronic diseases results in serious problems in public health worldwide.A growing body of evidence strongly indicate the close association between the pathogenesis of GLMD and the altered composition and function of intestinal microbiota.However,it is difficult to dissect the causative relationship between GLMD and intestinal microbiota in humans via clinical study.Therefore,the transplantation of human donor feces microbiota to animal models has been recognized as one of key approaches to reveal the cause-effect relationship between intervention therapies of Chinese Medicine or clinical characteristics and altered intestinal microbiota.This approach includes four major steps.Firstly,the intestinal microbiota should be isolated from human feces samples to prepare feces microbiota solution.Secondly,conditional germ-free mice will be induced by oral gavage of broad-spectrum antibiotic.Thirdly,conditional sterile mice was transplanted into specific bacterial species identified by whole flora or by metagenomic analysis,then was induced by animal models of metabolic diseases.Fourthly,the glucose and lipid metabolism phenotypes of the transplanted human intestinal flora were compared between the intervention group and the control group.As one of the frontier methods in the research of intestinal flora,the transplantation of human fecal microflora to animal models is of significant importance to the exploration of the mechanism underlying the therapeutic effect of Chinese medicine on GLMD.