Probiotic Mixture Ameliorates a Diet-Induced MASLD/MASH Murine Model through the Regulation of Hepatic Lipid...

Area of Science:

• Hepatology
• Microbiology
• Metabolic Diseases

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition lacking effective treatments.
• MASLD is a significant risk factor for hepatocellular carcinoma (HCC).
• The therapeutic potential of probiotics for MASLD and its progression to MASH is largely unexplored.

Purpose of the Study:

• To investigate the efficacy of a proprietary probiotic mixture, Prohep, in ameliorating MASLD and preventing its progression to MASH.
• To explore Prohep's effects on liver lipid accumulation, gut microbiome, bile acid profiles, and short-chain fatty acid levels in a murine model.

Main Methods:

• A high-fat diet (HFD)-induced MASLD/MASH murine model was utilized.
• Prohep was administered via voluntary intake.
• Analyses included liver steatosis assessment, plasma lipid profiling, gene expression analysis, gut microbiome profiling, bile acid analysis, and fecal SCFA quantification.

Main Results:

• Prohep alleviated HFD-induced liver steatosis and hepatic lipid accumulation.
• Prohep improved plasma lipid profiles by suppressing hepatic de novo lipogenesis and cholesterol biosynthesis genes.
• Prohep modulated the gut microbiome, altered bile acid profiles, and increased fecal SCFA levels.
• Prohep prevented the transition from MASLD to MASH by ameliorating hepatic steatosis, inflammation, and fibrosis in a prolonged HFD model.

Conclusions:

• Prohep demonstrates significant potential in ameliorating diet-induced MASLD and controlling the progression to MASH in mice.
• These findings support the development of Prohep as a novel microbial therapy for MASLD and MASH management.
• Prohep's mechanisms involve modulating lipid metabolism, gut microbiota, and related metabolites.