Hepatoprotective Effect of Probiotic Lactobacillus rhamnosus GG Through the Modulation of Gut Permeability and Inflammasomes in a Model of Alcoholic Liver Disease in Zebrafish

Abstract

Objective: Alcoholic liver disease (ALD) is among the leading causes of death from liver disease. Among the factors involved in its pathogenesis are inflammation and increased intestinal permeability. The aim of this study was to assess the effect of Lactobacillus rhamnosus GG (LGG) on hepatic lipid accumulation, activation of inflammasomes, and gut permeability markers in experimental model of ALD with zebrafish.

Methods: An experiment was conducted to assess the effective LGG dose capable of promoting intestinal colonization. Animals were divided into three groups (n = 64/group): ethanol group (E), ethanol + probiotic group (EP), and control group (C). Groups E and EP were exposed to 0.5% ethanol concentration for 28 days. At the end of this period, animals were euthanized, and livers were collected for Oil Red staining and assessment of the inflammasome system. Intestines were collected for evaluation of gut permeability markers.

Results: The dose of 1.55 × 10⁶ UFC LGG/fish/d promoted intestinal colonization. Group EP presented lower hepatic lipid accumulation, lower il-1β expression, and higher cldn15a expression when compared to group E.

Conclusions: Supplementation with LGG was protective for hepatic steatosis in ALD model. In addition, LGG influenced the modulation of the inflammatory response and markers of gut permeability, improving the gut barrier structure.

Keywords:

• probiotics
• Lactobacillus rhamnosus GG
• alcoholic liver disease
• inflammasomes
• zebrafish

Additional information

Funding

This study was supported by a grant from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), CHAMADA UNIVERSAL–MCTI/CNPq No. 14/2014 and Fundação Instituto de Pesquisas Econômicas (FIPE)/HCPA. The funders were not involved in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.