Bacterial translocation and changes in the intestinal microbiome in mouse models of liver disease

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• 作者：Derrick E. Fouts¹ ; Manolito Torralba¹ ; Karen E. Nelson¹ ; David A. Brenner² ; Bernd Schnabl² ; ^{beschnabl@ucsd.edu}
• 关键词：ALT ; alanine aminotransferase ; BDL ; bile duct ligation ; CCl4 ; carbon tetrachloride ; CFU ; colony-forming unit ; LBP ; lipopolysaccharide-binding protein ; PCoA ; Principal Coordinates Analysis ; LPS ; lipopolysaccharide ; OTU ; Operational Taxonomic Unit ; TLR ; Tol
• 刊名：Journal of Hepatology
• 出版年：2012
• 期刊代码：162_01688278
• 类别：med
• 出版时间：June, 2012
• 卷：56
• 期：6
• 页码：1283-1292
• 文件大小：858 K

摘要

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Background & Aims

Intestinal dysbiosis and bacterial translocation are 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.

Methods

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.

Results

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.

Conclusions

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.