GV-971 prevents severe acute pancreatitis by remodeling the microbiota-metabolic-immune axis

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.

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Publication Details

Journal
Nature Communications
Published
2024-09-27
DOI
https://doi.org/10.1038/s41467-024-52398-z
Citations
19
Primary Topic
Pancreatitis Pathology and Treatment
Type
article
Field-Weighted Citation Impact
10.88

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article

GV-971 prevents severe acute pancreatitis by remodeling the microbiota-metabolic-immune axis

Wen Fu, Yan Ding, Meixuan Wu, Jinheng Wang et al.
19 citations
Nature Communications
Pancreatitis Pathology and Treatment
10.88
article

GV-971 prevents severe acute pancreatitis by remodeling the microbiota-metabolic-immune axis

Wen Fu, Yan Ding, Meixuan Wu, Jinheng Wang, Jiangtuan Wang, Daolin Tang, Meiyu Geng, Feifei Ge, Xin Chen, Jinbao Liu, Xiaofen Li, Na Zhang, Xi Chen
article en
19 citations

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.

Nature CommunicationsVol. 15(1)
Chinese Academy of Sciences (CN), Second Affiliated Hospital of Guangzhou Medical University (CN), Southwestern Medical Center (US), Shanghai Institute of Materia Medica (CN), The University of Texas Southwestern Medical Center (US), Guangzhou Medical University (CN)
Guangzhou Medical University, State Key Laboratory of Respiratory Disease, National Natural Science Foundation of China
Good health and well-being
Openalex Percentile: Top 1%
Pancreatitis Pathology and Treatment
10.88
DOIOpen Access PDFOpenAlex
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