Intestinal mucosal barrier dysfunction participates in the progress of nonalcoholic fatty liver disease

Int J Clin Exp Pathol. 2015 Apr 1;8(4):3648-58. eCollection 2015.


Intestinal mucosal barrier dysfunction is closely related to liver diseases, which implies impaired gut-liver axis may play a role in the pathogenesis of NAFLD. In our study, rats were divided into three groups: normal chow diet (NCD) group, high-fat diet (HFD) group and TNBS-induced colitis with high-fat diet (C-HFD) group. Liver tissues were obtained for histological observation and TNF-α, IL-6 mRNA determination and blood samples were collected for liver enzymes and LPS analysis. Ultrastructural changes of jejuna epithelium, SIBO and amounts of CD103(+)MHCII(+)DCs and CD4(+)CD25(+)FoxP3(+)T-regs in terms of percentage in mesenteric lymph nodes (MLN) were observed by electron microscope, bacterial cultivation and flow cytometry, respectively. The results demonstrated the pathological characteristics accorded with nonalcoholic simple fatty liver (NAFL) and NASH in HFD group by week 8 and 12, respectively. Besides, the degree of hepatic steatosis and steatohepatitis was more severe in C-HFD group compared with HFD-group at the same time point. NAFLD activity score (NAS), liver enzymes, concentration of LPS and mRNA expressions of TNF-α, IL-6 were higher significantly in C-HFD group compared with HFD and NCD group at week 4, 8 and 12, respectively. In HFD group, epithelium microvilli atrophy, disruptive tight junctions and SIBO were present, and these changes were more severe in NASH compared with NAFL. The percentage of CD103+MHCII+DCs and CD4+CD25+FoxP3+T-regs decreased significantly in NAFL and NASH compared with NCD group. Our conclusion was that gut-liver axis was impaired in NAFLD, which played crucial role in the pathogenesis of NAFLD.

Keywords: IL-6; Nonalcoholic fatty liver disease; TNF-α; dendritic cell; intestinal mucosal barrier; regulatory T cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colitis / chemically induced
  • Colitis / immunology
  • Colitis / pathology*
  • Dendritic Cells / immunology
  • Diet, High-Fat / adverse effects
  • Disease Models, Animal
  • Disease Progression
  • Humans
  • Interleukin-6 / genetics
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / pathology
  • Liver / immunology
  • Liver / pathology
  • Male
  • Non-alcoholic Fatty Liver Disease / chemically induced
  • Non-alcoholic Fatty Liver Disease / immunology
  • Non-alcoholic Fatty Liver Disease / pathology*
  • Rats
  • Rats, Wistar
  • Signal Transduction / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Tumor Necrosis Factor-alpha / genetics


  • Interleukin-6
  • Tumor Necrosis Factor-alpha