Host-Microbiota Interactions in Liver Inflammation and Cancer

Area of Science:

• Gastroenterology and Hepatology
• Oncology
• Microbiology

Background:

• Hepatocellular carcinoma (HCC) is linked to chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD).
• These liver conditions share gut-related factors like dysbiosis, increased intestinal permeability, and altered metabolite profiles.
• Gut-derived microbial products and danger signals translocate to the liver, driving chronic inflammation and hepatic injury, promoting HCC.

Purpose of the Study:

• To review the communication pathways between the gut and liver.
• To elucidate mechanisms by which the intestinal microbiota promotes hepatic inflammation and HCC.
• To explore microbiota-targeted therapies for liver diseases and HCC.

Main Methods:

• Literature review focusing on gut-liver axis in liver disease and HCC.
• Analysis of mechanisms involving microbial products (MAMPs), host inflammatory responses, and microbial metabolites.
• Discussion of cell death and senescence pathways in tumor promotion.

Main Results:

• The gut microbiome plays a critical role in initiating and perpetuating liver inflammation.
• Microbial products, host inflammatory mediators, and altered host-microbiome metabolites contribute to HCC development.
• Gut dysbiosis and increased intestinal permeability are key drivers of liver pathology.

Conclusions:

• The gut-liver axis is central to HCC pathogenesis in chronic liver diseases.
• Microbial metabolites and inflammatory signals from the gut are crucial in promoting HCC.
• Modulating the gut microbiota presents a promising avenue for treating liver diseases and HCC.