高脂饮食HFA-小鼠肠道菌群结构和NF-κB炎症通路研究

摘要

The change of gut flora composition under the high fat diet and NF-κB inflammatory pathway were investigated with a high-fat diet fed human flora-associated mice (HFA-mice) model.The results of high-throughput sequencing before and after the experiments were showed in group 1,the composition ratio of dominant bacteria Bacteroides reduced from 61.9％ to 40.5％,and non-dominant bacteria (such as Akkermansia,Blautia,Dorea,Escherichia and Turicibacter) were 70.4,3.9,13.3,4.5 and 311 times that of the original ones,respectively.While Alistipes and Lactobacillus ratio were 1/10 and 1/5 of the original ones,respectively.In group 2,the composition ratio of Bacteroides increased from 31.2％ to 39.4％,and Parabacteroides reduced from 18.9％ to 8.4％.The results of reverse transcript-polymerase chain reaction (RT-PCR) showed that there was no significant difference between inflammatory cytokine levels (P＞0.05),but the expression quantity of NF-κB and PPARγ in group 1 were significantly higher than that of group 2.So it could be deduced that gut flora composition of"obese flora" HFA-mice was liable to be changed by high-fat diet,and the gut flora composition of"thin flora" HFA-mic relatively stable.The gut flora may cause inflammation by regulating the expression of NF-κB and PPARy genes.%通过胖瘦HFA-小鼠模型研究肠道菌群结构在高脂饮食下的变化及宿主炎症反应.实验前后高通量测序结果显示,1组小鼠优势菌相拟杆菌属(Bacteroides)的组成比例由61.9％降低为40.5％;非优势菌相中Akkermansia、Blautia、Dorea、埃希氏菌属(Escherichia)及Turicibacter5个菌属分别增加为原来的70.4、3.9、13.3、4.5和311倍;Alistipes和乳杆菌属(Lactobacillus)2个菌属减少为原来的1/10和1/5;2组小鼠肠道菌群拟杆菌属(Bacteroides)由31.2％增加为39.4％,Parabacteroides由18.9％降低为8.4％.逆转录聚合酶链反应(RT-PCR)结果显示,各组小鼠炎症因子水平无差异(P＞0.05),而第1组的相关调控基因NF-κB和PPARγ的表达量显著高于第2组(P＜0.05).因此推断,在属水平上,“胖菌群”HFA-小鼠肠道菌群容易受到高脂饮食的改变,“瘦菌群”HFA-小鼠肠道菌群结构相对稳定;肠道菌群可能通过影响PPARγ和NF-κB两个基因的表达而引起炎症反应.