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Intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans

BACKGROUND: Animal data suggest a role of the gut-liver axis in progression of alcoholic liver disease (ALD), but human data are scarce especially for early disease stages. METHODS: We included patients with alcohol use disorder (AUD) who follow a rehabilitation program and matched healthy controls....

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Autores principales: Maccioni, Luca, Gao, Bei, Leclercq, Sophie, Pirlot, Boris, Horsmans, Yves, De Timary, Philippe, Leclercq, Isabelle, Fouts, Derrick, Schnabl, Bernd, Stärkel, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524402/
https://www.ncbi.nlm.nih.gov/pubmed/32588725
http://dx.doi.org/10.1080/19490976.2020.1782157
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author Maccioni, Luca
Gao, Bei
Leclercq, Sophie
Pirlot, Boris
Horsmans, Yves
De Timary, Philippe
Leclercq, Isabelle
Fouts, Derrick
Schnabl, Bernd
Stärkel, Peter
author_facet Maccioni, Luca
Gao, Bei
Leclercq, Sophie
Pirlot, Boris
Horsmans, Yves
De Timary, Philippe
Leclercq, Isabelle
Fouts, Derrick
Schnabl, Bernd
Stärkel, Peter
author_sort Maccioni, Luca
collection PubMed
description BACKGROUND: Animal data suggest a role of the gut-liver axis in progression of alcoholic liver disease (ALD), but human data are scarce especially for early disease stages. METHODS: We included patients with alcohol use disorder (AUD) who follow a rehabilitation program and matched healthy controls. We determined intestinal epithelial and vascular permeability (IP) (using urinary excretion of (51)Cr-EDTA, fecal albumin content, and immunohistochemistry in distal duodenal biopsies), epithelial damage (histology, serum iFABP, and intestinal gene expression), and microbial translocation (Gram – and Gram + serum markers by ELISA). Duodenal mucosa-associated microbiota and fecal microbiota were analyzed by 16 S rRNA sequencing. ALD was staged by Fibroscan® (liver stiffness, controlled attenuation parameter) in combination with serum AST, ALT, and CK18-M65. RESULTS: Only a subset of AUD patients had increased (51)Cr-EDTA and fecal albumin together with disrupted tight junctions and vasculature expression of plasmalemma Vesicle-Associated Protein-1. The so-defined increased intestinal permeability was not related to changes of the duodenal microbiota or alterations of the intestinal epithelium but associated with compositional changes of the fecal microbiota. Leaky gut alone did not explain increased microbial translocation in AUD patients. By contrast, duodenal dysbiosis with a dominance shift toward specific potential pathogenic bacteria genera (Streptococcus, Shuttleworthia, Rothia), increased IP and elevated markers of microbial translocation characterized AUD patients with progressive ALD (steato-hepatitis, steato-fibrosis). CONCLUSION: Progressive ALD already at early disease stages is associated with duodenal mucosa-associated dysbiosis and elevated microbial translocation. Surprisingly, such modifications were not linked with increased IP. Rather, increased IP appears related to fecal microbiota dysbiosis.
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spelling pubmed-75244022020-10-06 Intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans Maccioni, Luca Gao, Bei Leclercq, Sophie Pirlot, Boris Horsmans, Yves De Timary, Philippe Leclercq, Isabelle Fouts, Derrick Schnabl, Bernd Stärkel, Peter Gut Microbes Research Paper BACKGROUND: Animal data suggest a role of the gut-liver axis in progression of alcoholic liver disease (ALD), but human data are scarce especially for early disease stages. METHODS: We included patients with alcohol use disorder (AUD) who follow a rehabilitation program and matched healthy controls. We determined intestinal epithelial and vascular permeability (IP) (using urinary excretion of (51)Cr-EDTA, fecal albumin content, and immunohistochemistry in distal duodenal biopsies), epithelial damage (histology, serum iFABP, and intestinal gene expression), and microbial translocation (Gram – and Gram + serum markers by ELISA). Duodenal mucosa-associated microbiota and fecal microbiota were analyzed by 16 S rRNA sequencing. ALD was staged by Fibroscan® (liver stiffness, controlled attenuation parameter) in combination with serum AST, ALT, and CK18-M65. RESULTS: Only a subset of AUD patients had increased (51)Cr-EDTA and fecal albumin together with disrupted tight junctions and vasculature expression of plasmalemma Vesicle-Associated Protein-1. The so-defined increased intestinal permeability was not related to changes of the duodenal microbiota or alterations of the intestinal epithelium but associated with compositional changes of the fecal microbiota. Leaky gut alone did not explain increased microbial translocation in AUD patients. By contrast, duodenal dysbiosis with a dominance shift toward specific potential pathogenic bacteria genera (Streptococcus, Shuttleworthia, Rothia), increased IP and elevated markers of microbial translocation characterized AUD patients with progressive ALD (steato-hepatitis, steato-fibrosis). CONCLUSION: Progressive ALD already at early disease stages is associated with duodenal mucosa-associated dysbiosis and elevated microbial translocation. Surprisingly, such modifications were not linked with increased IP. Rather, increased IP appears related to fecal microbiota dysbiosis. Taylor & Francis 2020-06-26 /pmc/articles/PMC7524402/ /pubmed/32588725 http://dx.doi.org/10.1080/19490976.2020.1782157 Text en © 2020 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
spellingShingle Research Paper
Maccioni, Luca
Gao, Bei
Leclercq, Sophie
Pirlot, Boris
Horsmans, Yves
De Timary, Philippe
Leclercq, Isabelle
Fouts, Derrick
Schnabl, Bernd
Stärkel, Peter
Intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans
title Intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans
title_full Intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans
title_fullStr Intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans
title_full_unstemmed Intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans
title_short Intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans
title_sort intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524402/
https://www.ncbi.nlm.nih.gov/pubmed/32588725
http://dx.doi.org/10.1080/19490976.2020.1782157
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