The role of gut vascular barrier in experimental alcoholic liver disease and A. muciniphila supplementation

Gut Microbes. 2020 Nov 9;12(1):1851986. doi: 10.1080/19490976.2020.1851986.

Abstract

The translocation of bacterial components from the intestinal lumen into the portal circulation is crucial in the pathogenesis of alcoholic liver disease (ALD). Recently the important role of the gut vascular barrier (GVB) was elucidated in alcoholic liver disease. Here we report about the influence of A. muciniphila supplementation in experimental ALD on the GVB. Ethanol feeding was associated with increased Pv-1, indicating altered endothelial barrier function, whereas A. muciniphila administration tended to restore GVB. To further investigate GVB in experimental ALD, β-catenin gain-of-function mice, which display an enhanced GVB, were ethanol-fed. β-catenin gain-of-function mice were not protected from ethanol-induced liver injury, suggest an alternative mechanism of ethanol-induced GVB disruption. The description of the GVB in ALD could pave the way for new therapeutic options in the future.

Keywords: Akkermansia muciniphila; Gut vascular barrier; alcoholic liver disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Akkermansia / physiology
  • Animals
  • Bacterial Translocation
  • Disease Models, Animal
  • Female
  • Gastrointestinal Microbiome*
  • Humans
  • Intestines / blood supply*
  • Intestines / microbiology
  • Liver Diseases, Alcoholic / drug therapy*
  • Liver Diseases, Alcoholic / microbiology
  • Mice
  • Probiotics / administration & dosage*

Supplementary concepts

  • Akkermansia muciniphila

Grants and funding

H.T. is supported by the excellence initiative VASCage (Centre for Promoting Vascular Health in the Ageing Community), an R&D K-Centre (COMET program - Competence Centers for Excellent Technologies) funded by the Austrian Ministry for Transport, Innovation and Technology, the Austrian Ministry for Digital and Economic Affairs and the federal states Tyrol, Salzburg and Vienna. M.R. is supported by the ERC (Grant agreement No. 615735 homeoGUT) AIRC (IG 22026 2018), AIRC 5 × 1000 (UniCanVax 22757).