6) Br J Pharmacol. 2018 Feb;175(3):469-484.

Tauroursodeoxycholic acid inhibits intestinal inflammation and barrier disruption in mice with non-alcoholic fatty liver disease

Weijun Wang ¹, Jinfang Zhao ¹, Wenfang Gui ¹, Dan Sun ², Haijiang Dai ³, Li Xiao ¹, Huikuan Chu ¹, Fan Du ¹, Qingjing Zhu ⁴, Bernd Schnabl ⁵, Kai Huang ², Ling Yang ¹, Xiaohua Hou ¹

Abstract

Background and purpose: The gut-liver axis is associated with the progression of non-alcoholic fatty liver disease (NAFLD). Targeting the gut-liver axis and bile acid-based pharmaceuticals are potential therapies for NAFLD. The effect of tauroursodeoxycholic acid (TUDCA), a candidate drug for NAFLD, on intestinal barrier function, intestinal inflammation, gut lipid transport and microbiota composition was analysed in a murine model of NAFLD.

Experimental approach: The NAFLD mouse model was established by feeding mice a high-fat diet (HFD) for 16 weeks. TUDCA was administered p.o. during the last 4 weeks. The expression levels of intestinal tight junction genes, lipid metabolic and inflammatory genes were determined by quantitative PCR. Tissue inflammation was evaluated by haematoxylin and eosin staining. The gut microbiota was analysed by 16S rRNA gene sequencing.

Key results: TUDCA administration attenuated HFD-induced hepatic steatosis, inflammatory responses, obesity and insulin resistance in mice. Moreover, TUDCA attenuated gut inflammatory responses as manifested by decreased intestinal histopathology scores and inflammatory cytokine levels. In addition, TUDCA improved intestinal barrier function by increasing levels of tight junction molecules and the solid chemical barrier. The components involved in ileum lipid transport were also reduced by TUDCA administration in HFD-fed mice. Finally, the TUDCA-treated mice showed a different gut microbiota composition compared with that in HFD-fed mice but similar to that in normal chow diet-fed mice.

Conclusions and implications: TUDCA attenuates the progression of HFD-induced NAFLD in mice by ameliorating gut inflammation, improving intestinal barrier function, decreasing intestinal fat transport and modulating intestinal microbiota composition.