Distinctly altered gut microbiota in the progression of liver disease

Oncotarget. 2016 Apr 12;7(15):19355-66. doi: 10.18632/oncotarget.8466.


Recent studies underscore important roles of intestinal microbiota and the bacterial lipopolysaccharides (LPS) production in the pathogenesis of liver disease. However, how gut microbiota alters in response to the development of steatosis and subsequent progression to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remains unclear. We aimed to study the gut microbial changes over liver disease progression using a streptozotocin-high fat diet (STZ-HFD) induced NASH-HCC C57BL/6J mouse model that is highly relevant to human liver disease. The fecal microbiota at various liver pathological stages was analyzed by 16S rDNA gene pyrosequencing. Both UniFrac analysis and partial least squares-discriminant analysis showed significant structural alterations in gut microbiota during the development of liver disease. Co-abundance network analysis highlighted relationships between genera. Spearman correlation analysis revealed that the bacterial species, Atopobium spp., Bacteroides spp., Bacteroides vulgatus, Bacteroides acidifaciens, Bacteroides uniformis, Clostridium cocleatum, Clostridium xylanolyticum and Desulfovibrio spp., markedly increased in model mice, were positively correlated with LPS levels and pathophysiological features. Taken together, the results showed that the gut microbiota was altered significantly in the progression of liver disease. The connection between the gut microbial ecology and the liver pathology may represent potential targets for the prevention and treatment of chronic liver disease and HCC.

Keywords: Immune response; Immunity; Immunology and Microbiology Section; gut microbiota; lipopolysaccharides; liver disease; pathogenesis.

MeSH terms

  • Animals
  • Animals, Newborn
  • Bacteria / classification
  • Bacteria / genetics
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / physiopathology*
  • Disease Models, Animal
  • Disease Progression
  • Feces / microbiology
  • Gastrointestinal Microbiome / genetics
  • Gastrointestinal Microbiome / physiology*
  • Humans
  • Liver Diseases / pathology
  • Liver Diseases / physiopathology
  • Liver Neoplasms / pathology
  • Liver Neoplasms / physiopathology*
  • Male
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / pathology
  • Non-alcoholic Fatty Liver Disease / physiopathology*
  • RNA, Ribosomal, 16S / genetics
  • Sequence Analysis, DNA


  • RNA, Ribosomal, 16S