Bacterial translocation and changes in the intestinal microbiome in mouse models of liver disease.
Bacterial translocation and changes in the intestinal microbiome in mouse models of liver disease.
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DOI：
10.1016/j.jhep.2012.01.019
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发表时间：
2012-06
影响因子：
25.7
通讯作者：
Schnabl, Bernd
中科院分区：
文献类型：
--
作者：
Fouts, Derrick E.;Torralba, Manolito;Nelson, Karen E.;Brenner, David A.;Schnabl, Bernd
肠道微生物失调和细菌易位在晚期肝病患者中很常见，有强有力的证据表明，细菌及其产物跨越上皮屏障的易位推动了实验性肝病的进展。我们研究的目的是研究肝病早期肠道微生物群中细菌易位的动态变化。结扎胆总管(BDL)造成小鼠胆汁淤积性肝损伤，四氯化碳(CCl4)致小鼠中毒性肝损伤。在两种疾病模型中，肝损伤后一天，肠道通透性增加和细菌易位。伴随而来的是紧密连接蛋白occludin在肠道的表达减少。尽管BDL导致肠道细菌迅速过度生长，但在注射CCl4的小鼠中，只有在肝纤维化晚期才观察到细菌过度生长。为了进一步评估肠道微生物组的质量变化，对16S rRNA基因的大规模平行焦解测序显示，BDL后微生物发生了轻微变化，而与石油注射小鼠相比，CCl4注射导致了相对丰富的微生物和放线杆菌。四种不同的肝病模型(胆汁淤积、中毒、酒精、肥胖)在其肠道微生物群中显示出很少的相似之处。急性肝损伤与肠道通透性增加和细菌易位的早期发病有关，这些都先于微生物组的变化。肠道微生物群在肝病的病因方面是不同的。
Intestinal dysbiosis and bacterial translocation is common in patients with advanced liver disease, and there is strong evidence that the translocation of bacteria and their products across the epithelial barrier drives experimental liver disease progression. The aims of our study were to investigate dynamics of bacterial translocation and changes in the enteric microbiome in early stages of liver disease. Cholestatic liver injury was induced by ligation of the common bile duct (BDL) and toxic liver injury by injection of carbon tetrachloride (CCl4) in mice. Increased intestinal permeability and bacterial translocation occurred one day following liver injury in both disease models. This was accompanied by decreased intestinal expression of the tight junction protein occludin. Although BDL resulted in a rapid onset of intestinal bacterial overgrowth, bacterial overgrowth was observed in mice injected with CCl4 only in advanced stages of liver fibrosis. To further assess the qualitative changes in the intestinal microbiome, massively parallel pyrosequencing of 16S rRNA genes revealed minor microbial changes following BDL, while CCl4 administration resulted in a relative abundance of Firmicutes and Actinobacteria compared with oil injected mice. Four different liver disease models (cholestasis, toxic, alcohol, obesity) show few similarities in their intestinal microbiome. Acute liver injury is associated with an early onset of increased intestinal permeability and bacterial translocation that precede changes in the microbiome. The enteric microbiome differs with respect to the etiology of liver disease.
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影响因子：
64.8
作者：
Brandl, Katharina;Plitas, George;Mihu, Coralia N.;Ubeda, Carles;Jia, Ting;Fleisher, Martin;Schnabl, Bernd;DeMatteo, Ronald P.;Pamer, Eric G.
通讯作者：
Pamer, Eric G.
Toll样受体4的肝硬化预测单核苷酸多态性与肝星状细胞反应的功能联系。
影响因子：
13.5
作者：
Guo, Jinsheng;Loke, Johnny;Zheng, Feng;Hong, Feng;Yea, Steven;Fukata, Masayuki;Tarocchi, Mirko;Abar, Olivia T.;Huang, Hongjin;Sninsky, John J.;Friedman, Scott L.
通讯作者：
Friedman, Scott L.
影响因子：
13.5
作者：
Frances, Ruben;Zapater, Pedro;Such, Jose
通讯作者：
Such, Jose
影响因子：
9.8
作者：
Bauer, TM;Steinbrückner, B;Blum, HE
通讯作者：
Blum, HE
影响因子：
13.5
作者：
Chang, CS;Chen, GH;Yeh, HZ
通讯作者：
Yeh, HZ