高脂饮食HFA-小鼠肠道菌群结构和NF-κB炎症通路研究

Gut flora composition and NF-κB inflammatory pathway of high-fat diet HFA-mice

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Turicibacter 5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。

The change of gut flora composition under the high fat diet and NF-KB 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 fi＇om 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 PPAR＇y 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 PPAR＇y genes.