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Semin Liver Dis 2021; 41(02): 191-205
DOI: 10.1055/s-0041-1723752
Review Article

Gut–Liver Axis in Nonalcoholic Fatty Liver Disease: the Impact of the Metagenome, End Products, and the Epithelial and Vascular Barriers

Antonio Gil-Gómez
1   SeLiver Group at Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital/CSIC/University of Seville, Seville, Spain
2   Hepatic and Digestive Diseases Networking Biomedical Research Centre (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
,
Paola Brescia
3   Humanitas Clinical and Research Center – IRCCS, Rozzano, Milan, Italy
,
Maria Rescigno
3   Humanitas Clinical and Research Center – IRCCS, Rozzano, Milan, Italy
,
Manuel Romero-Gómez
1   SeLiver Group at Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital/CSIC/University of Seville, Seville, Spain
2   Hepatic and Digestive Diseases Networking Biomedical Research Centre (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
4   UCM Digestive Diseases, Virgen del Rocío University Hospital, Seville, Spain
› Author Affiliations Funding This project has been partially funded by the “Asociación Española para el Estudio del Hígado” (Beca de Aprendizaje de Nuevas Tecnologías) and the “Spanish Ministry of Economy, Innovation, and Competition, Instituto de Salud Carlos III” (PI19/00589). The funders have not had any role in the design, writing, or interpretation of this project.
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Abstract

Nonalcoholic fatty liver disease (NAFLD) is a systemic, dynamic, heterogeneous, and multiaxis entity, the pathogenesis of which is still uncertain. The gut–liver axis is regulated and stabilized by a complex network encompassing a metabolic, immune, and neuroendocrine cross-talk between the gut, the microbiota, and the liver. Changes in the gut–liver axis affect the metabolism of lipids and carbohydrates in the hepatocytes, and they impact the balance of inflammatory mediators and cause metabolic deregulation, promoting NAFLD and its progression to nonalcoholic steatohepatitis. Moreover, the microbiota and its metabolites can play direct and indirect roles in gut barrier function and fibrosis development. In this review, we will highlight findings from the recent literature focusing on the gut–liver axis and its relation to NAFLD. Finally, we will discuss the impact of technical issues, design bias, and other limitations on current knowledge of the gut microbiota in the context of NAFLD.

Keywords

Microbiota - Microbiome - NAFLD - NASH - Gut–Liver axis


Publication History

Article published online:
08 March 2021

© 2021. Thieme. All rights reserved.

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