Inhibition of microbial deconjugation of micellar bile acids protects against intestinal permeability and liver injury

Li et al. (BioRxiv) doi: 10.1101/2021.03.24.436896

Keywords

  • Intestinal barrier

  • Liver disease

  • Bile acid

 

Main Findings

Rats on a high-fat diet exhibit increased intestinal permeability and liver injury, as well as reduced levels of conjugated bile acids. In-vitro, conjugated bile acids are responsible for protection of the epithelial layer from damage induced by unconjugated bile acid formation of micelles. Inhibition of bile acid deconjugation led to reduced intestinal permeability and liver injury in high fat diet fed mice. 

Limitations

  • In-vitro assays using Caco-2 cells are not entirely relevant in-vivo, and use of mucusoids/organoids would have strengthened these experiments.

  • Micelle formation is identified as the mechanism of injury in-vitro, but isn’t show in-vivo. 

Significance/Novelty

  • The identification of a microbial-specific mechanism of bile acids driving damage to the intestinal barrier during liver injury is of therapeutic interest, and has advanced the field of liver disease.

Credit

Reviewed by India Brough as part of the cross-institutional journal club of the Immunology Institute of the Icahn School of Medicine, Mount Sinai and the Kennedy Institute of Rheumatology, University of Oxford and Karolinska Institute. Follow her on Twitter.