Akkermansia Muciniphila Suppresses Non-alcoholic Steatohepatitis-associated Liver Cancer in Mice by Recovering Intestinal Barrier Function

Objective To investigate whether the next-generation probiotics Akkermansia muciniphila can prevent non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC).

Methods We constructed a NASH-HCC model called STAM. STAM mice received oral saline or A. muciniphila starting at 4 weeks of age. Liver tissues were evaluated by HE staining and oil red O staining for NASH activity, and intrahepatic expression levels of inflammatory cytokines and ileal tight junction proteins were measured by RT-PCR.

Results At 8 weeks of age, the steatosis, ballooning degeneration and NAS scores, TNF-α, MCP-1, IL-1β, and IL-6 mRNA expression were significantly decreased in the STAM+A. muciniphila group (both P < 0.05) compared with those in the STAM+saline group (all P < 0.05). At 20 weeks of age, the number of liver surface tumors formed, tumor size and IL-6 level were decreased in the STAM + A. muciniphila group (all P < 0.05). A. muciniphila restored the thickness of the colon mucosal layer and the number of goblet cells in STAM mice as well as increased the mRNA expression of the tight junction proteins ZO-1, Claudin-3, and Occludin in ileal epithelial cells.

Conclusion Akkermansia muciniphila can inhibit the progression of NASH to HCC by improving the intestinal barrier function and may serve as a candidate drug to prevent NASH-HCC.