Inhibition of microbial deconjugation of micellar bile acids protects against intestinal permeability and liver injury
Li D.K. et al. (BioRxiv) DOI: 10.1101/2021.03.24.436896
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.
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.
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.
Reviewed by India Brough as part of the cross-institutional journal club of the Immunology Institute of the Icahn School of Medicine, Mount Sinai, the Kennedy Institute of Rheumatology and the Oxford Centre for Immuno-Oncology (OXCIO) (University of Oxford, GB) and Karolinska Institute’s Center for Infectious Medicine (CIM) & Center for Molecular Medicine (CMM). Follow her on Twitter.