Co-exposure to different bacterial species’ lipopolysaccharides with the NASH diet exacerbates NASH and liver fibrosis progression in mice

Abstract

Background and aim

With the obesity epidemic, nonalcoholic fatty liver disease (NAFLD) has become a public health concern, but its progression mechanism remains unclear. Experimental models mimicking human NAFLD/steatohepatitis (NASH) are crucial. This study simulates gut microbiota imbalance effects on NASH and liver fibrosis.

Methods

We used different bacterial sources of lipopolysaccharide (LPS), including Escherichia coli (GEC) and Salmonella abortus equi (GSE), combined with a Gubra Amylin NASH (GAN) diet to induce NASH and liver fibrosis.

Results

The GSE group showed significantly higher serum alanine aminotransferase, hydroxyproline, CD68-positive cells, α-smooth muscle actin, glial fibrillary acidic protein, and TNF-α, COL1A1, TGF-β, and NLRP3 expressions compared to the the GAN group. The GSE group also had higher Erysipelotrichaceae, Akkermansiaceae, and Bacteroidaceae family numbers.

Conclusions

The GAN diet with LPS treatment successfully induced NASH and fibrosis making this model useful for preclinical NASH drug testing.