The role of the microbiome in  NAFLD  and  NASH

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Nonalcoholic fatty liver disease ( NAFLD) is the hepatic manifestation of cardiometabolic syndrome, which often also includes obesity, diabetes, and dyslipidemia. It is rapidly becoming the most prevalent liver disease worldwide. A sizable minority of NAFLD patients develop nonalcoholic steatohepatitis ( NASH), which is characterized by inflammatory changes that can lead to progressive liver damage, cirrhosis, and hepatocellular carcinoma. Recent studies have shown that in addition to genetic predisposition and diet, the gut microbiota affects hepatic carbohydrate and lipid metabolism as well as influences the balance between pro‐inflammatory and anti‐inflammatory effectors in the liver, thereby impacting NAFLD and its progression to NASH. In this review, we will explore the impact of gut microbiota and microbiota‐derived compounds on the development and progression of NAFLD and NASH, and the unexplored factors related to potential microbiome contributions to this common liver disease.

Related collections

Most cited references 62

Record: found
Abstract: found
Article: not found

Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis.

Christopher J Sinal, Masahiro Tohkin, Masaaki Miyata … (2000)

Mice lacking the nuclear bile acid receptor FXR/BAR developed normally and were outwardly identical to wild-type littermates. FXR/BAR null mice were distinguished from wild-type mice by elevated serum bile acid, cholesterol, and triglycerides, increased hepatic cholesterol and triglycerides, and a proatherogenic serum lipoprotein profile. FXR/BAR null mice also had reduced bile acid pools and reduced fecal bile acid excretion due to decreased expression of the major hepatic canalicular bile acid transport protein. Bile acid repression and induction of cholesterol 7alpha-hydroxylase and the ileal bile acid binding protein, respectively, did not occur in FXR/BAR null mice, establishing the regulatory role of FXR/BAR for the expression of these genes in vivo. These data demonstrate that FXR/BAR is critical for bile acid and lipid homeostasis by virtue of its role as an intracellular bile acid sensor.

0 comments Cited 391 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide

Kymberleigh A. Romano, Eugenio I. Vivas, Daniel Amador-Noguez … (2015)

ABSTRACT Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which upon absorption by the host is converted in the liver to trimethylamine-N-oxide (TMAO). Recent studies revealed that TMAO exacerbates atherosclerosis in mice and positively correlates with the severity of this disease in humans. However, which microbes contribute to TMA production in the human gut, the extent to which host factors (e.g., genotype) and diet affect TMA production and colonization of these microbes, and the effects TMA-producing microbes have on the bioavailability of dietary choline remain largely unknown. We screened a collection of 79 sequenced human intestinal isolates encompassing the major phyla found in the human gut and identified nine strains capable of producing TMA from choline in vitro. Gnotobiotic mouse studies showed that TMAO accumulates in the serum of animals colonized with TMA-producing species, but not in the serum of animals colonized with intestinal isolates that do not generate TMA from choline in vitro. Remarkably, low levels of colonization by TMA-producing bacteria significantly reduced choline levels available to the host. This effect was more pronounced as the abundance of TMA-producing bacteria increased. Our findings provide a framework for designing strategies aimed at changing the representation or activity of TMA-producing bacteria in the human gut and suggest that the TMA-producing status of the gut microbiota should be considered when making recommendations about choline intake requirements for humans.

0 comments Cited 294 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Bile acids and nonalcoholic fatty liver disease: Molecular insights and therapeutic perspectives

Juan Arab, Saul J Karpen, Paul Dawson … (2016)

Nonalcoholic fatty liver disease (NAFLD) is a burgeoning health problem worldwide and an important risk factor for both hepatic and cardiometabolic mortality. The rapidly increasing prevalence of this disease and of its aggressive form nonalcoholic steatohepatitis (NASH) will require novel therapeutic approaches to prevent disease progression to advanced fibrosis or cirrhosis and cancer. In recent years, bile acids have emerged as relevant signaling molecules that act at both hepatic and extrahepatic tissues to regulate lipid and carbohydrate metabolic pathways as well as energy homeostasis. Activation or modulation of bile acid receptors, such as the farnesoid X receptor and TGR5, and transporters, such as the ileal apical sodium‐dependent bile acid transporter, appear to affect both insulin sensitivity and NAFLD/NASH pathogenesis at multiple levels, and these approaches hold promise as novel therapies. In the present review, we summarize current available data on the relationships of bile acids to NAFLD and the potential for therapeutically targeting bile‐acid‐related pathways to address this growing world‐wide disease. (Hepatology 2017;65:350‐362)

0 comments Cited 252 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Eran Elinav:

ORCID: https://orcid.org/0000-0002-5775-2110

eran.elinav@weizmann.ac.il

Journal

Journal ID (nlm-ta): EMBO Mol Med

Journal ID (iso-abbrev): EMBO Mol Med

Journal ID (doi): 10.1002/(ISSN)1757-4684

Journal ID (publisher-id): EMMM

Journal ID (hwp): embomm

Title: EMBO Molecular Medicine

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 1757-4676

ISSN (Electronic): 1757-4684

Publication date (Electronic): 27 December 2018

Publication date (Print): February 2019

Volume: 11

Issue: 2 ( doiID: 10.1002/emmm.v11.2 )

Electronic Location Identifier: e9302

Affiliations

[ ¹ ] Immunology Department Weizmann Institute of Science Rehovot Israel

[ ² ] Department of Gastroenterology The First Affiliated Hospital Sun Yat‐sen University Guangzhou China

[ ³ ] Department of Gastroenterology and Liver Disease Tel Aviv Sourasky Medical Center Tel Aviv Israel

[ ⁴ ] Sackler Faculty of Medicine Tel Aviv Sourasky Medical Center Tel Aviv Israel

Author notes

[*] [* ]Corresponding author. Tel: +972 08 934 4014; E‐mail: eran.elinav@ 123456weizmann.ac.il

[†]

These authors contributed equally to this work

Author information

Eran Elinav https://orcid.org/0000-0002-5775-2110

Article

Publisher ID: EMMM201809302

DOI: 10.15252/emmm.201809302

PMC ID: 6365925

PubMed ID: 30591521

SO-VID: 00f857db-4e36-4613-8434-326c5b9a2467

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

History

Date received : 17 September 2018

Date revision received : 14 November 2018

Date accepted : 03 December 2018

Page count

Figures: 2, Tables: 0, Pages: 13, Words: 11702

Funding

Funded by: European Union's Horizon 2020

Award ID: 747114

Funded by: European Crohn's and Colitis Organization (ECCO) Fellowship

Funded by: Ke Lin Program of the First Affiliated Hospital of Sun Yat‐sen University

Funded by: Alexander Grass foundation

Funded by: Y. and R. Ungar

Funded by: Gurwin Family Fund for Scientific Research

Funded by: Crown Endowment Fund for Immunological Research

Funded by: Else Kroener‐Fresenius Foundation

Funded by: Benoziyo Endowment Fund for the Advancement of Science

Funded by: Adelis Foundation

Funded by: French National Center for Scientific Research (CNRS)

Funded by: European Research Council

Funded by: Marie Curie Integration grant

Funded by: Rising Tide Foundation

Funded by: Helmholtz Foundation

Funded by: Canadian Institute of Advanced Research (CIFAR)

Funded by: The Bill & Melinda Gates Foundation & Howard Hughes Medical Institute (HHMI)

Funded by: Abisch‐Frenkel Foundation for the Promotion of Life Sciences

Funded by: Leona M. and Harry B. Helmsley Charitable Trust

Funded by: German–Israeli Foundation for Scientific Research and Development

Funded by: Israel Science Foundation

Funded by: Minerva Foundation

Funded by: European Foundation for the Study of Diabetes

Custom metadata

source-schema-version-number 2.0

component-id emmm201809302

cover-date February 2019

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_NLMPMC version:5.5.8 mode:remove_FC converted:07.02.2019

ScienceOpen disciplines: Molecular medicine

Keywords: microbiome/microbiota,nonalcoholic fatty liver disease,nonalcoholic steatohepatitis,digestive system,microbiology, virology & host pathogen interaction

Data availability:

ScienceOpen disciplines: Molecular medicine

Keywords: microbiome/microbiota, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, digestive system, microbiology, virology & host pathogen interaction

The role of the microbiome in NAFLD and NASH

Read this article at

Abstract

Related collections

Bacterial extracellular vesicles

Most cited references 62

Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis.

Intestinal Microbiota Composition Modulates Choline Bioavailability from Diet and Accumulation of the Proatherogenic Metabolite Trimethylamine-N-Oxide

Bile acids and nonalcoholic fatty liver disease: Molecular insights and therapeutic perspectives

Author and article information

Contributors

Journal

Affiliations

Author notes

Author information

Article

History

Page count

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 488

Cited by 182

Most referenced authors 2,167