Akkermansia muciniphila in the small intestine improves liver fibrosis and hyperammonemia in a murine liver cirrhosis model

Liver cirrhosis (LC) is a crucial global health issue. LC leads to various critical morbidity including hepatic encephalopathy (HE). While the gut microbiota is considered involved in the pathogenesis of LC, underlying mechanisms remain unestablished. We conceived to investigate the microbiome in multiple sites of the GI tract to obtain insights into the association between the gut microbiota and LC and HE. The relationship between the clinical efficacy and alterations of bacterial compositions along the GI tract by antibiotics 'rifaximin (RFX)' was investigated. The clinical efficacy of RFX was associated with increases in specific bacterial genera in the small intestine including Akkermansia. A strain of Akkermansia muciniphila (A. muciniphila) administration improved liver fibrosis and hyperammonemia in the murine LC model. This study proposed that microbiota ecology in the small intestine plays a role in the pathophysiology of liver fibrosis and HE and oral administration of A. muciniphila is promising as a microbial intervention for these conditions.