Pasteurized Akkermansia muciniphila and its outer membrane protein Amuc_1100 alleviate alcoholic liver disease through modulating gut microbiota and host metabolism

Abstract

Recent researches have reported that pasteurized Akkermansia muciniphila, as a paraprobiotic, still plays an active role in various metabolic diseases. However, its role in alcoholic liver disease (ALD) remains unexplored. This study aims to evaluate the impact and mechanisms of pasteurized A. muciniphila on ALD. Its effects on ALD were assessed by phenotypic, biochemical parameters, and histological features in a mouse model. Further investigations into underlying mechanisms were conducted through gut microbiome, metabolomics analyses and quantitative real-time polymerase chain reaction (qRT-PCR) technology. Heterologously expressed outer membrane protein Amuc_1100 was utilized to explore the molecular action mechanism. Our research demonstrated that pasteurized A. muciniphila can indeed alleviate alcohol-induced liver damage by modulation of gut microbiota and host metabolism. It suppressed the proliferation of pathogenic microbes and fostered the growth of probiotics. Additionally, it rectified alcohol-induced abnormalities in serum metabolic patterns, particularly in lipid metabolism. Specifically, pasteurized A. muciniphila elevated serum levels of 3-hydroxybutyric acid, palmitoleic acid, acetylcarnitine, DHA, and arachidonic acid in alcohol-fed mice. qRT-PCR results showed that it reversed the alcohol-induced upregulation of mRNA expression of hepatic fatty acid synthesis genes and decreased mRNA expression of fatty acid oxidation and transport genes. Importantly, we identified that Amuc_1100 could partially recapitulate the protective effects of pasteurized A. muciniphila on ALD, especially regarding hepatic lipid metabolism. This study enhances our comprehension of the function of pasteurized A. muciniphila and underscores its potential therapeutic application, along with Amuc_1100, in the treatment of ALD.