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Immune Response of an Oral Enterococcus faecalis Phage Cocktail in a Mouse Model of Ethanol-Induced Liver Disease

Cytolysin-positive Enterococcus faecalis (E. faecalis) cause more severe alcohol-associated hepatitis, and phages might be used to specifically target these bacteria in a clinical trial. Using a humanized mouse model of ethanol-induced liver disease, the effect of cytolytic E. faecalis phage treatme...

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Autores principales: Mendes, Beatriz Garcia, Duan, Yi, Schnabl, Bernd
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955932/
https://www.ncbi.nlm.nih.gov/pubmed/35336897
http://dx.doi.org/10.3390/v14030490
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author Mendes, Beatriz Garcia
Duan, Yi
Schnabl, Bernd
author_facet Mendes, Beatriz Garcia
Duan, Yi
Schnabl, Bernd
author_sort Mendes, Beatriz Garcia
collection PubMed
description Cytolysin-positive Enterococcus faecalis (E. faecalis) cause more severe alcohol-associated hepatitis, and phages might be used to specifically target these bacteria in a clinical trial. Using a humanized mouse model of ethanol-induced liver disease, the effect of cytolytic E. faecalis phage treatment on the intestinal and liver immune response was evaluated. The observed immune response was predominantly anti-inflammatory and tissue-restoring. Besides, live phages could be readily recovered from the serum, spleen, and liver following oral gavage in ethanol-fed mice. We also isolated 20 new phages from the sewage water; six of them exhibited a relatively broad host range. Taken together, the oral administration of cytolytic E. faecalis phages leads to the translocation of phages to the systemic circulation and appears to be safe, following chronic-binge ethanol administration. A cocktail of three phages covers the majority of tested cytolysin-positive E. faecalis strains and could be tested in a clinical trial.
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spelling pubmed-89559322022-03-26 Immune Response of an Oral Enterococcus faecalis Phage Cocktail in a Mouse Model of Ethanol-Induced Liver Disease Mendes, Beatriz Garcia Duan, Yi Schnabl, Bernd Viruses Article Cytolysin-positive Enterococcus faecalis (E. faecalis) cause more severe alcohol-associated hepatitis, and phages might be used to specifically target these bacteria in a clinical trial. Using a humanized mouse model of ethanol-induced liver disease, the effect of cytolytic E. faecalis phage treatment on the intestinal and liver immune response was evaluated. The observed immune response was predominantly anti-inflammatory and tissue-restoring. Besides, live phages could be readily recovered from the serum, spleen, and liver following oral gavage in ethanol-fed mice. We also isolated 20 new phages from the sewage water; six of them exhibited a relatively broad host range. Taken together, the oral administration of cytolytic E. faecalis phages leads to the translocation of phages to the systemic circulation and appears to be safe, following chronic-binge ethanol administration. A cocktail of three phages covers the majority of tested cytolysin-positive E. faecalis strains and could be tested in a clinical trial. MDPI 2022-02-27 /pmc/articles/PMC8955932/ /pubmed/35336897 http://dx.doi.org/10.3390/v14030490 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mendes, Beatriz Garcia
Duan, Yi
Schnabl, Bernd
Immune Response of an Oral Enterococcus faecalis Phage Cocktail in a Mouse Model of Ethanol-Induced Liver Disease
title Immune Response of an Oral Enterococcus faecalis Phage Cocktail in a Mouse Model of Ethanol-Induced Liver Disease
title_full Immune Response of an Oral Enterococcus faecalis Phage Cocktail in a Mouse Model of Ethanol-Induced Liver Disease
title_fullStr Immune Response of an Oral Enterococcus faecalis Phage Cocktail in a Mouse Model of Ethanol-Induced Liver Disease
title_full_unstemmed Immune Response of an Oral Enterococcus faecalis Phage Cocktail in a Mouse Model of Ethanol-Induced Liver Disease
title_short Immune Response of an Oral Enterococcus faecalis Phage Cocktail in a Mouse Model of Ethanol-Induced Liver Disease
title_sort immune response of an oral enterococcus faecalis phage cocktail in a mouse model of ethanol-induced liver disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8955932/
https://www.ncbi.nlm.nih.gov/pubmed/35336897
http://dx.doi.org/10.3390/v14030490
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