Modeling dysbiosis of human NASH in mice: Loss of gut microbiome diversity and overgrowth of Erysipelotrichales.

<h4>Background & aim</h4>Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD) that is responsible for a growing fraction of cirrhosis and liver cancer cases worldwide. Changes in the gut microbiome have been implicated in NASH pathogenesi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	James K Carter, Dipankar Bhattacharya, Joshua N Borgerding, M Isabel Fiel, Jeremiah J Faith, Scott L Friedman
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/60b207e17bac473783c80497954c0aa0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:60b207e17bac473783c80497954c0aa0
record_format	dspace
spelling	oai:doaj.org-article:60b207e17bac473783c80497954c0aa02021-12-02T20:04:09ZModeling dysbiosis of human NASH in mice: Loss of gut microbiome diversity and overgrowth of Erysipelotrichales.1932-620310.1371/journal.pone.0244763https://doaj.org/article/60b207e17bac473783c80497954c0aa02021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0244763https://doaj.org/toc/1932-6203<h4>Background & aim</h4>Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD) that is responsible for a growing fraction of cirrhosis and liver cancer cases worldwide. Changes in the gut microbiome have been implicated in NASH pathogenesis, but the lack of suitable murine models has been a barrier to progress. We have therefore characterized the microbiome in a well-validated murine NASH model to establish its value in modeling human disease.<h4>Methods</h4>The composition of intestinal microbiota was monitored in mice on a 12- or 24-week NASH protocol consisting of high fat, high sugar Western Diet (WD) plus once weekly i.p injection of low-dose CCl4. Additional mice were subjected to WD-only or CCl4-only conditions to assess the independent effect of these variables on the microbiome.<h4>Results</h4>There was substantial remodeling of the intestinal microbiome in NASH mice, characterized by declines in both species diversity and bacterial abundance. Based on changes to beta diversity, microbiota from NASH mice clustered separately from controls in principal coordinate analyses. A comparison between WD-only and CCl4-only controls with the NASH model identified WD as the primary driver of early changes to the microbiome, resulting in loss of diversity within the 1st week. A NASH signature emerged progressively at weeks 6 and 12, including, most notably, a reproducible bloom of the Firmicute order Erysipelotrichales.<h4>Conclusions</h4>We have established a valuable model to study the role of gut microbes in NASH, enabling us to identify a new NASH gut microbiome signature.James K CarterDipankar BhattacharyaJoshua N BorgerdingM Isabel FielJeremiah J FaithScott L FriedmanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 1, p e0244763 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q James K Carter Dipankar Bhattacharya Joshua N Borgerding M Isabel Fiel Jeremiah J Faith Scott L Friedman Modeling dysbiosis of human NASH in mice: Loss of gut microbiome diversity and overgrowth of Erysipelotrichales.
description	<h4>Background & aim</h4>Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD) that is responsible for a growing fraction of cirrhosis and liver cancer cases worldwide. Changes in the gut microbiome have been implicated in NASH pathogenesis, but the lack of suitable murine models has been a barrier to progress. We have therefore characterized the microbiome in a well-validated murine NASH model to establish its value in modeling human disease.<h4>Methods</h4>The composition of intestinal microbiota was monitored in mice on a 12- or 24-week NASH protocol consisting of high fat, high sugar Western Diet (WD) plus once weekly i.p injection of low-dose CCl4. Additional mice were subjected to WD-only or CCl4-only conditions to assess the independent effect of these variables on the microbiome.<h4>Results</h4>There was substantial remodeling of the intestinal microbiome in NASH mice, characterized by declines in both species diversity and bacterial abundance. Based on changes to beta diversity, microbiota from NASH mice clustered separately from controls in principal coordinate analyses. A comparison between WD-only and CCl4-only controls with the NASH model identified WD as the primary driver of early changes to the microbiome, resulting in loss of diversity within the 1st week. A NASH signature emerged progressively at weeks 6 and 12, including, most notably, a reproducible bloom of the Firmicute order Erysipelotrichales.<h4>Conclusions</h4>We have established a valuable model to study the role of gut microbes in NASH, enabling us to identify a new NASH gut microbiome signature.
format	article
author	James K Carter Dipankar Bhattacharya Joshua N Borgerding M Isabel Fiel Jeremiah J Faith Scott L Friedman
author_facet	James K Carter Dipankar Bhattacharya Joshua N Borgerding M Isabel Fiel Jeremiah J Faith Scott L Friedman
author_sort	James K Carter
title	Modeling dysbiosis of human NASH in mice: Loss of gut microbiome diversity and overgrowth of Erysipelotrichales.
title_short	Modeling dysbiosis of human NASH in mice: Loss of gut microbiome diversity and overgrowth of Erysipelotrichales.
title_full	Modeling dysbiosis of human NASH in mice: Loss of gut microbiome diversity and overgrowth of Erysipelotrichales.
title_fullStr	Modeling dysbiosis of human NASH in mice: Loss of gut microbiome diversity and overgrowth of Erysipelotrichales.
title_full_unstemmed	Modeling dysbiosis of human NASH in mice: Loss of gut microbiome diversity and overgrowth of Erysipelotrichales.
title_sort	modeling dysbiosis of human nash in mice: loss of gut microbiome diversity and overgrowth of erysipelotrichales.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/60b207e17bac473783c80497954c0aa0
work_keys_str_mv	AT jameskcarter modelingdysbiosisofhumannashinmicelossofgutmicrobiomediversityandovergrowthoferysipelotrichales AT dipankarbhattacharya modelingdysbiosisofhumannashinmicelossofgutmicrobiomediversityandovergrowthoferysipelotrichales AT joshuanborgerding modelingdysbiosisofhumannashinmicelossofgutmicrobiomediversityandovergrowthoferysipelotrichales AT misabelfiel modelingdysbiosisofhumannashinmicelossofgutmicrobiomediversityandovergrowthoferysipelotrichales AT jeremiahjfaith modelingdysbiosisofhumannashinmicelossofgutmicrobiomediversityandovergrowthoferysipelotrichales AT scottlfriedman modelingdysbiosisofhumannashinmicelossofgutmicrobiomediversityandovergrowthoferysipelotrichales
_version_	1718375604831649792

Modeling dysbiosis of human NASH in mice: Loss of gut microbiome diversity and overgrowth of Erysipelotrichales.

Ejemplares similares