Colesevelam Reduces Ethanol-Induced Liver Steatosis in Humanized Gnotobiotic Mice

  • Cells. 2021 Jun 14;10(6):1496. doi: 10.3390/cells10061496.
Noemí Cabré  1 ,  Yi Duan  1 ,  Cristina Llorente  1 ,  Mary Conrad  2 ,  Patrick Stern  2 ,  Dennis Yamashita  2 ,  Bernd Schnabl  1  3
Affiliations
  • 1. Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
  • 2. Axial Therapeutics, Woburn, MA 01801, USA.
  • 3. Department of Medicine, VA San Diego Healthcare System, San Diego, CA 92161, USA.
PMID: 34198609 DOI: 10.3390/cells10061496
Abstract

Alcohol-related liver disease is associated with intestinal dysbiosis. Functional changes in the microbiota affect bile acid metabolism and result in elevated serum bile acids in patients with alcohol-related liver disease. The aim of this study was to identify the potential role of the bile acid sequestrant colesevelam in a humanized mouse model of ethanol-induced liver disease. We colonized germ-free (GF) C57BL/6 mice with feces from patients with alcoholic hepatitis and subjected humanized mice to the chronic-binge ethanol feeding model. Ethanol-fed gnotobiotic mice treated with colesevelam showed reduced hepatic levels of triglycerides and Cholesterol, but liver injury and inflammation were not decreased as compared with non-treated mice. Colesevelam reduced hepatic Cytochrome P450, family 7, subfamily a, polypeptide 1 (Cyp7a1) protein expression, although serum bile acids were not lowered. In conclusion, our findings indicate that colesevelam treatment mitigates ethanol-induced liver steatosis in mice.

Keywords
CYP7A1; alcoholic liver disease; bile acids; microbiome.
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