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.

Keywords: Fibrosis; Gut microbiota; Hepatic inflammatory; LPS; Nonalcoholic steatohepatitis.