Akkermansia muciniphila alleviates high-fat-diet-related metabolic-associated fatty liver disease by modulating gut microbiota and bile acids.

It has been reported that Akkermansia muciniphila improves host metabolism and reduces inflammation; however, its potential effects on bile acid metabolism and metabolic patterns in metabolic-associated fatty liver disease (MAFLD) are unknown. In this study, we have analysed C57BL/6 mice under three feeding conditions: (i) a low-fat diet group (LP), (ii) a high-fat diet group (HP) and (iii) a high-fat diet group supplemented with A. muciniphila (HA). The results found that A. muciniphila administration relieved weight gain, hepatic steatosis and liver injury induced by the high-fat diet. A. muciniphila altered the gut microbiota with a decrease in Alistipes, Lactobacilli, Tyzzerella, Butyricimonas and Blautia, and an enrichment of Ruminiclostridium, Osclibacter, Allobaculum, Anaeroplasma and Rikenella. The gut microbiota changes correlated significantly with bile acids. Meanwhile, A. muciniphila also improved glucose tolerance, gut barriers and adipokines dysbiosis. Akkermansia muciniphila regulated the intestinal FXR-FGF15 axis and reshaped the construction of bile acids, with reduced secondary bile acids in the caecum and liver, including DCA and LCA. These findings provide new insights into the relationships between probiotics, microflora and metabolic disorders, highlighting the potential role of A. muciniphila in the management of MAFLD.