Akkermansia muciniphila inhibits jejunal lipid absorption and regulates jejunal core bacteria

Insufficiency of Akkermansia muciniphila (Akk) has been implicated in the pathogenesis of metabolic diseases, and administration or restoration of Akk has ameliorated these disorders. Recently, Pasteurized Akk (PA-Akk) has been approved as a functional food. However, the impact of Akk on lipid absorption in the proximal intestine, which is directly exposed to orally administered Akk, remains largely unexplored. In this study, we orally administered Akk and PA-Akk to mice and investigated the subsequent lipid absorption. Long-term administration of Akk resulted in reduced lipid deposits in the liver and adipocytes, along with improved glucose metabolism. This was primarily attributed to a reduction in lipid absorption by epithelial cells in the proximal jejunum. Mechanistically, Akk activated AMP-activated protein kinase (AMPK) and directly inhibit lipids absorption in both mouse and human jejunal epithelial cells. Furthermore, we demonstrated that Akk treatment, but not PA-Akk treatment, promotes the abundance of genera that are highly abundant in the normal jejunum and belong to the phylum Firmicutes. Thus, our study concludes that oral administration of Akk provides beneficial effects on metabolism, partially through inhibiting jejunal lipid absorption and promoting the abundance of core jejunal microbes.