Akkermansia muciniphila reduces lipid absorption through activating AMPK in the jejunum

Akkermansia muciniphila (Akk) associated with multiple metabolic diseases and administration of Akk can improve the metabolic disorders. However, little is known about the effect of Akk on jejunal epithelial cells which absorb lipid and interact with oral administrated Akk. We oral administrated Akk to mice and measured the lipid absorption and gene expression in small intestinal epithelial cells. The long-term effect of Akk treatment reduced lipid deposits in the liver and adipocytes with improved the glucose metabolism. This is particularly caused by reduced lipid absorption in jejunal epithelia. Akk feeding reduced the expression of those genes that regulate synthesis and cell cycles, characters of the host cell responding to energy deficiency. In fact, we detected increased AMPK-alpha phosphorylation levels in Akk-treated jejunal epithelial cells both in vivo and in vitro. Furthermore, activating AMPK inhibits lipids absorption in jejunum. Thus, we conclude that oral administration of Akk activates the AMPK pathway and represses the lipid absorption in jejunal epithelial cells, which contributes to the metabolic benefits of oral Akk administration. The mice were fed with normal chow diet. At the age of 8 weeks old, we orally administrated 4x10^8 Akk to mice dailly for 7 weeks. Then, the intestine epithelial cells were collected followed by RNA extraction and RNAseq. The control group oraaly administrated with PBS.