Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 27, 2021; 13(12): 2052-2070
Published online Dec 27, 2021. doi: 10.4254/wjh.v13.i12.2052
Gut dysbiosis and systemic inflammation promote cardiomyocyte abnormalities in an experimental model of steatohepatitis
Larisse Longo, Pabulo Henrique Rampelotto, Eduardo Filippi-Chiela, Valessa Emanoele Gabriel de Souza, Fernando Salvati, Carlos Thadeu Cerski, Themis Reverbel da Silveira, Cláudia P Oliveira, Carolina Uribe-Cruz, Mário Reis Álvares-da-Silva
Larisse Longo, Pabulo Henrique Rampelotto, Valessa Emanoele Gabriel de Souza, Themis Reverbel da Silveira, Carolina Uribe-Cruz, Mário Reis Álvares-da-Silva, Experimental Laboratory of Hepatology and Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Rio Grande do Sul, Brazil
Larisse Longo, Eduardo Filippi-Chiela, Carlos Thadeu Cerski, Carolina Uribe-Cruz, Mário Reis Álvares-da-Silva, Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-003, Rio Grande do Sul, Brazil
Pabulo Henrique Rampelotto, Graduate Program in Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Porto Alegre 90035-903, Rio Grande do Sul, Brazil
Eduardo Filippi-Chiela, Center of Biotechnology, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Rio Grande do Sul, Brazil
Eduardo Filippi-Chiela, Department of Morphological Sciences, Universidade Federal do Rio Grande do SulPorto Alegre 90050-170, Rio Grande do Sul, Brazil
Eduardo Filippi-Chiela, Experimental Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Rio Grande do Sul, Brazil
Fernando Salvati, School of Medicine, Instituto Meridional de Educação-IMED, Passo Fundo 99070-220, Rio Grande do Sul, Brazil
Carlos Thadeu Cerski, Unit of Surgical Pathology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Rio Grande do Sul, Brazil
Cláudia P Oliveira, Department of Gastroenterology (LIM07), Faculdade de Medicina da Universidade de São Paulo, São Paulo 01246903, Brazil
Mário Reis Álvares-da-Silva, Division of Gastroenterology, Hospital de Clínicas de Porto Alegre, Porto Alegre 90035-903, Rio Grande do Sul, Brazil
Author contributions: Longo L, Rampelotto PH, Filippi-Chiela E and Álvares-da-Silva MR performed the conceptualization, methodology, formal analysis, investigation, data curation, writing of the original draft, writing-review, and editing; de Souza VEG, Salvati F, and Cerski CT performed the conceptualization, methodology, and formal analysis; da Silveira TR, Oliveira CP and Uribe-Cruz C contributed to the conceptualization, data curation writing the original draft, writing-review and editing.
Institutional review board statement: IRB approval was obtained for this study from the Grupo de Pesquisa em Pós-Graduação – Comissão de Ética em Uso Animal do Hospital de Clínicas de Porto Alegre.
Institutional animal care and use committee statement: All experimental procedures were approved by the Ethics Committee for the Use of Animals (No. 17-0021 and No. 17-0531) in accordance with international guidelines for animal welfare and measures were taken to minimize animal pain and discomfort.
Conflict-of-interest statement: The authors declare that they have no competing interests.
Data sharing statement: If requested and after approval, the authors authorize data sharing.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Larisse Longo, PhD, Postdoc, Experimental Laboratory of Hepatology and Gastroenterology, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350/Sala 12214, 2° Andar, Porto Alegre 90035-903, Rio Grande do Sul, Brazil. larisselongo@hotmail.com
Received: April 1, 2021
Peer-review started: April 1, 2021
First decision: July 16, 2021
Revised: July 20, 2021
Accepted: October 18, 2021
Article in press: October 18, 2021
Published online: December 27, 2021
ARTICLE HIGHLIGHTS
Research background

Metabolic-associated fatty liver disease (MAFLD), in addition to being a progressive liver disease, is an independent and significant risk factor for the development of cardiovascular disease, and dysbiosis of the intestinal microbiota is associated with both.

Research motivation

The motivation was to explore the mechanisms whereby gut microbiota contribute to steatohepatitis-associated increased cardiovascular risk.

Research objectives

The objective was to assess the relationship between gut dysbiosis and cardiovascular risk in an experimental model of steatohepatitis.

Research methods

Adult male Sprague-Dawley rats were randomized to a control group given a standard diet or an intervention of a high-fat and choline-deficient diet for 16 wk of ten animals each. Biochemical, molecular, hepatic, and cardiac histopathology and gut microbiota variables were evaluated.

Research results

We reported significant correlations between the presence of atherogenic dyslipidemia, systemic inflammation, endothelial dysfunction, liver fibrogenesis and gut dysbiosis, all of which contributed to the progression of MAFLD and increased CVR.

Research conclusions

This study shows that there is a link between gut dysbiosis and significant cardiomyocyte abnormalities in animals with steatohepatitis.

Research perspectives

Metabolomic studies may aid in elucidating the association of gut microbial function with the development of cardiometabolic disorders related to steatohepatitis. The gut microbiota may be a potential therapeutic target for both clinical conditions.