Effects of rifaximin-α on liver phenotype in murine models of early stage alcohol-associated and metabolic-dysfunction associated steatotic liver disease

Background Alcohol-associated (ArLD) and metabolic dysfuncion-associated fatty liver disease (MASLD) are currently the leading causes for chronic liver diseases in the Western world. Rifaximin-α is a non-absorbable antibiotic and in clinical use in advanced chronic liver disease for the treatment of hepatic encephalopathy. In this study, we aim to investigate the effects of rifaximin-α on the liver phenotype in different murine models of early stage ArLD and MASLD.

Methods 12-week-old, C57Bl/6 mice were treated for 7 weeks with either a Methionine-Choline deficient diet (MCD), Western diet (WD), carbon tetrachloride (CCl4) inhalations or standard chow (n=20). Half of the mice were assigned to receive additionally ethanol. Every group was further divided whether to receive rifaximin-α (30 µg/mouse/day) or not. After sacrifice, livers were analyzed in order to determine fibrosis, inflammation, proliferation and steatosis through (immuno-)histochemistry, qPCR and photometric assays for hydroxyproline and triglycerides.

Results As expected, CCl4 treatment induced the strongest liver fibrosis. MCD treatment led to decreased body weight as well as liver steatosis and fibrosis. Additionally, ethanol increased fibrosis in MCD-treated animals, but decreased fibrosis in WD-fed mice. Rifaximin-α did not have any effect on liver fibrosis or steatosis, but a mild increase in proinflammatory transcripts were observed in MCD-based, WD+ethanol and ethanol-treated animals. In ethanol, MCD+ethanol and WD-treated mice, rifaximin-α treatment led to an increasing trend in hepatic proliferation.

Conclusion Liver fibrosis and steatosis of MCD- and WD-induced early murine MASLD and ArLD did not change during rifaximin-α treatment. However, mild changes in hepatic inflammation were observed.

Publication History

Article published online:
23 January 2024