Cargando…

Dietary Synbiotic Supplementation Protects Barrier Integrity of Hepatocytes and Liver Sinusoidal Endothelium in a Mouse Model of Chronic-Binge Ethanol Exposure

Alcohol overconsumption disrupts the gut microbiota and intestinal barrier, which decreases the production of beneficial microbial metabolic byproducts and allows for translocation of pathogenic bacterial-derived byproducts into the portal-hepatic circulation. As ethanol is known to damage liver sin...

Descripción completa

Detalles Bibliográficos
Autores principales: Han, Yingchun, Glueck, Bryan, Shapiro, David, Miller, Aaron, Roychowdhury, Sanjoy, Cresci, Gail A. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071303/
https://www.ncbi.nlm.nih.gov/pubmed/32023885
http://dx.doi.org/10.3390/nu12020373
_version_ 1783506170887012352
author Han, Yingchun
Glueck, Bryan
Shapiro, David
Miller, Aaron
Roychowdhury, Sanjoy
Cresci, Gail A. M.
author_facet Han, Yingchun
Glueck, Bryan
Shapiro, David
Miller, Aaron
Roychowdhury, Sanjoy
Cresci, Gail A. M.
author_sort Han, Yingchun
collection PubMed
description Alcohol overconsumption disrupts the gut microbiota and intestinal barrier, which decreases the production of beneficial microbial metabolic byproducts and allows for translocation of pathogenic bacterial-derived byproducts into the portal-hepatic circulation. As ethanol is known to damage liver sinusoidal endothelial cells (LSEC), here we evaluated dietary supplementation with a previously studied synbiotic on gut microbial composition, and hepatocyte and LSEC integrity in mice exposed to ethanol. We tested a chronic-binge ethanol feeding mouse model in which C57BL/6 female mice were fed ethanol (5% vol/vol) for 10 days and provided a single ethanol gavage (5 g/kg body weight) on day 11, 6 h before euthanasia. An ethanol-treatment group also received oral supplementation daily with a synbiotic; and an ethanol-control group received saline. Control mice were pair-fed and isocalorically substituted maltose dextran for ethanol over the entire exposure period; they received a saline gavage daily. Ethanol exposure decreased gut microbial abundance and diversity. This was linked with diminished expression of adherens junction proteins in hepatocytes and dysregulated expression of receptors for advanced glycation end-products; and this coincided with reduced expression of endothelial barrier proteins. Synbiotic supplementation mitigated these effects. These results demonstrate synbiotic supplementation, as a means to modulate ethanol-induced gut dysbiosis, is effective in attenuating injury to hepatocyte and liver endothelial barrier integrity, highlighting a link between the gut microbiome and early stages of acute liver injury in ethanol-exposed mice.
format Online
Article
Text
id pubmed-7071303
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-70713032020-03-19 Dietary Synbiotic Supplementation Protects Barrier Integrity of Hepatocytes and Liver Sinusoidal Endothelium in a Mouse Model of Chronic-Binge Ethanol Exposure Han, Yingchun Glueck, Bryan Shapiro, David Miller, Aaron Roychowdhury, Sanjoy Cresci, Gail A. M. Nutrients Article Alcohol overconsumption disrupts the gut microbiota and intestinal barrier, which decreases the production of beneficial microbial metabolic byproducts and allows for translocation of pathogenic bacterial-derived byproducts into the portal-hepatic circulation. As ethanol is known to damage liver sinusoidal endothelial cells (LSEC), here we evaluated dietary supplementation with a previously studied synbiotic on gut microbial composition, and hepatocyte and LSEC integrity in mice exposed to ethanol. We tested a chronic-binge ethanol feeding mouse model in which C57BL/6 female mice were fed ethanol (5% vol/vol) for 10 days and provided a single ethanol gavage (5 g/kg body weight) on day 11, 6 h before euthanasia. An ethanol-treatment group also received oral supplementation daily with a synbiotic; and an ethanol-control group received saline. Control mice were pair-fed and isocalorically substituted maltose dextran for ethanol over the entire exposure period; they received a saline gavage daily. Ethanol exposure decreased gut microbial abundance and diversity. This was linked with diminished expression of adherens junction proteins in hepatocytes and dysregulated expression of receptors for advanced glycation end-products; and this coincided with reduced expression of endothelial barrier proteins. Synbiotic supplementation mitigated these effects. These results demonstrate synbiotic supplementation, as a means to modulate ethanol-induced gut dysbiosis, is effective in attenuating injury to hepatocyte and liver endothelial barrier integrity, highlighting a link between the gut microbiome and early stages of acute liver injury in ethanol-exposed mice. MDPI 2020-01-31 /pmc/articles/PMC7071303/ /pubmed/32023885 http://dx.doi.org/10.3390/nu12020373 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Han, Yingchun
Glueck, Bryan
Shapiro, David
Miller, Aaron
Roychowdhury, Sanjoy
Cresci, Gail A. M.
Dietary Synbiotic Supplementation Protects Barrier Integrity of Hepatocytes and Liver Sinusoidal Endothelium in a Mouse Model of Chronic-Binge Ethanol Exposure
title Dietary Synbiotic Supplementation Protects Barrier Integrity of Hepatocytes and Liver Sinusoidal Endothelium in a Mouse Model of Chronic-Binge Ethanol Exposure
title_full Dietary Synbiotic Supplementation Protects Barrier Integrity of Hepatocytes and Liver Sinusoidal Endothelium in a Mouse Model of Chronic-Binge Ethanol Exposure
title_fullStr Dietary Synbiotic Supplementation Protects Barrier Integrity of Hepatocytes and Liver Sinusoidal Endothelium in a Mouse Model of Chronic-Binge Ethanol Exposure
title_full_unstemmed Dietary Synbiotic Supplementation Protects Barrier Integrity of Hepatocytes and Liver Sinusoidal Endothelium in a Mouse Model of Chronic-Binge Ethanol Exposure
title_short Dietary Synbiotic Supplementation Protects Barrier Integrity of Hepatocytes and Liver Sinusoidal Endothelium in a Mouse Model of Chronic-Binge Ethanol Exposure
title_sort dietary synbiotic supplementation protects barrier integrity of hepatocytes and liver sinusoidal endothelium in a mouse model of chronic-binge ethanol exposure
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071303/
https://www.ncbi.nlm.nih.gov/pubmed/32023885
http://dx.doi.org/10.3390/nu12020373
work_keys_str_mv AT hanyingchun dietarysynbioticsupplementationprotectsbarrierintegrityofhepatocytesandliversinusoidalendotheliuminamousemodelofchronicbingeethanolexposure
AT glueckbryan dietarysynbioticsupplementationprotectsbarrierintegrityofhepatocytesandliversinusoidalendotheliuminamousemodelofchronicbingeethanolexposure
AT shapirodavid dietarysynbioticsupplementationprotectsbarrierintegrityofhepatocytesandliversinusoidalendotheliuminamousemodelofchronicbingeethanolexposure
AT milleraaron dietarysynbioticsupplementationprotectsbarrierintegrityofhepatocytesandliversinusoidalendotheliuminamousemodelofchronicbingeethanolexposure
AT roychowdhurysanjoy dietarysynbioticsupplementationprotectsbarrierintegrityofhepatocytesandliversinusoidalendotheliuminamousemodelofchronicbingeethanolexposure
AT crescigailam dietarysynbioticsupplementationprotectsbarrierintegrityofhepatocytesandliversinusoidalendotheliuminamousemodelofchronicbingeethanolexposure