A purified membrane protein Amuc_1098 from Akkermansia muciniphila blunts acute pancreatitis by modulation of intestinal flora and glycerophospholipid metabolism

Abstract

Amuc_1098 is a membrane protein from Akkermansia muciniphila. In this study, we investigated how Amuc_1098 affects acute pancreatitis (AP) in mice induced by caerulein and lipopolysaccharide (LPS). Treating mice with Amuc_1098 (3 μg, i.g.) for 20 days before caerulein and LPS injection reduced pancreatic injury and lowered serum amylase and lipase levels. Amuc_1098 supplementation reduced proinflammatory cytokines (TNF-α, IL-1β and IL-6) in spleen and pancreas by inhibiting NF-κB signaling. It also decreased Ly6C+ macrophages in the spleen and pancreas of AP mice. Amuc_1098 pretreatment reversed declined tight junction proteins in the colon of AP mice. Glycerophospholipid metabolism was significantly increased in patients and mice with AP. We further demonstrated that oral administration of Amuc_1098 reduced glycerophospholipid metabolism enrichment mediated by intestinal flora. These results provide new evidence that Amuc_1098 lessens the severity of AP through its anti-inflammatory properties with a reduction of macrophage infiltration in spleen and pancreas, an elevation of tight junction proteins in the colon, as well as its regulation of the composition of intestinal flora and glycerophospholipid metabolism.