GV-971 prevents severe acute pancreatitis by remodeling the microbiota-metabolic-immune axis
Xi Chen, Xin Chen, Yan Ding, Na Zhang, Wen Fu, Meixuan Wu, Feifei Ge, Jiangtuan Wang, Xiaofen Li, Meiyu Geng, Jinheng Wang, Daolin Tang, Jinbao Liu, Daolin Tang, Jinbao Liu
Abstract
Despite recent advances, severe acute pancreatitis (SAP) remains a lethal inflammation with limited treatment options. Here, we provide compelling evidence of GV-971 (sodium oligomannate), an anti-Alzheimer’s medication, as being a protective agent in various male mouse SAP models. Microbiome sequencing, along with intestinal microbiota transplantation and mass cytometry technology, unveil that GV-971 reshapes the gut microbiota, increasing Faecalibacterium populations and modulating both peripheral and intestinal immune systems. A metabolomics analysis of cecal contents from GV-971–treated SAP mice further identifies short-chain fatty acids, including propionate and butyrate, as key metabolites in inhibiting macrophage M1 polarization and subsequent lethal inflammation by blocking the MAPK pathway. These findings suggest GV-971 as a promising therapeutic for SAP by targeting the microbiota metabolic immune axis. Severe acute pancreatitis (SAP) is a profoundly lethal inflammatory condition with limited therapeutic options. Here, the authors present GV-971, an anti-Alzheimer's medication, as a promising candidate for SAP by effectively restoring intestinal microbiota homeostasis and metabolite profiles.