Different bacteria species lipopolysaccharide co-exposure with NASH diet exacerbate NASH and liver fibrosis progress in mice.

Abstract

Background and aim: Given the obesity epidemic, nonalcoholic fatty liver disease has become a public health concern; however, the progression mechanism remains obscure. Therefore, experimental nonalcoholic fatty liver disease/steatohepatitis (NASH) animal models that reflect human disease are necessary. In this study, we simulated the effects of gut microbiota imbalance on NASH and liver fibrosis.

Methods: Different bacterial sources of lipopolysaccharide, including Escherichia coli (GEC) and Salmonella abortus equi (GSE), were combined with a Gubra Amylin NASH (GAN) diet to induce NASH and liver fibrosis.

Results: Serum levels of alanine aminotransferase, hydroxyproline, CD68-positive cells, α-smooth muscle actin, and glial fibrillary acidic protein as well as TNF-α, COL1A1, TGF-β, and NLRP3 expressions in the livers of the GSE group were markedly increased compared to those in the GAN group. The GAN diet with lipopolysaccharide (LPS) treatment resulted in a marked difference in microbiota α-diversity. The GSE group had higher numbers ofincreased Erysipelotrichaceae, Akkermansiaceae, and Bacteroidaceae families than the other groups.

Conclusions: Based on these results, the GAN diet combined with LPS treatment successfully induced the progression of liver disease to NASH and fibrosis. With consistent histologically proven fibrosis, this obese NASH mouse model has relatively good clinical translatability and is highly applicable for preclinical drug testing for NASH.