Bile acid metabolomics identifies chenodeoxycholic acid as a therapeutic agent for pancreatic necrosis
Qingtian Zhu, Chenchen Yuan, Xiaowu Dong, Yaodong Wang, Baiqiang Li, Bo Tu, Weiwei Chen, Xingmeng Xu, Weijuan Gong, Weiming Xiao, Yanbing Ding, Liang‐Hao Hu, Weiqin Li, Guotao Lu
Abstract
Bile acids are altered and associated with prognosis in patients with acute pancreatitis (AP). Here, we conduct targeted metabolomic analyses to detect bile acids changes in patients during the acute (n = 326) and the recovery (n = 133) phases of AP, as well as in healthy controls (n = 60). Chenodeoxycholic acid (CDCA) decreases in the acute phase, increases in the recovery phase, and is associated with pancreatic necrosis. CDCA and its derivative obeticholic acid exhibit a protective effect against acinar cell injury in vitro and pancreatic necrosis in murine models, and RNA sequencing reveals that the oxidative phosphorylation pathway is mainly involved. Moreover, we find that overexpression of farnesoid X receptor (FXR, CDCA receptor) inhibits pancreatic necrosis, and interfering expression of FXR exhibits an opposite phenotype in mice. Our results possibly suggest that targeting CDCA is a potential strategy for the treatment of acinar cell necrosis in AP, but further verification is needed.