Rifaximin Protects Against Inflammation and Fibrosis in MASH: Any Role for Ethanol-Producing Bacteria?

Area of Science:

• Hepatology and Gastroenterology
• Microbiology and Immunology

Background:

• Metabolic Dysfunction-Associated Steato-Hepatitis (MASH) is a complex liver disease exacerbated by gut microbiota metabolites like endotoxins and ethanol.
• Rifaximin, an antibiotic, is being investigated for its potential to modulate gut microbiota and impact MASH progression.

Purpose of the Study:

• To investigate the efficacy of rifaximin in ameliorating MASH progression in a Western diet-induced mouse model.
• To determine if rifaximin's protective effects are mediated by reducing ethanol-producing colonic bacteria.

Main Methods:

• Thirty mice were divided into three groups: normal diet, Western diet, and Western diet with rifaximin.
• After 12 weeks, liver function, serum inflammatory markers (TNF-α, IL-1β, IL-6, LPS), and liver pathology were assessed.
• Faecal ethanol content, gut bacteria composition, and bacterial sensitivity to rifaximin were evaluated.

Main Results:

• Rifaximin treatment significantly improved liver function, reduced serum inflammatory markers, and attenuated liver steatosis, inflammation, and fibrosis.
• Expressions of liver injury markers (p53, GFAP, CD68, TLR-4) were reduced by rifaximin.
• Rifaximin did not decrease faecal ethanol or ethanol-producing bacteria; isolated bacteria showed rifaximin resistance.

Conclusions:

• Rifaximin demonstrates a protective effect in a MASH mouse model, likely through reducing endotoxemia and liver inflammation.
• The protective mechanism is not mediated by altering ethanol-producing colonic bacteria due to acquired rifaximin resistance.
• Further research is needed to understand the precise mechanisms of rifaximin's benefits in MASH.