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

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  • Xi Chen

    (State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University)

  • Xin Chen

    (State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University
    Therapy and Rehabilitation of Guangdong Higher Education Institutes, The Fifth Affiliated Hospital, Guangzhou Medical University)

  • Ding Yan

    (State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University)

  • Na Zhang

    (State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University)

  • Wen Fu

    (State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University)

  • Meixuan Wu

    (State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University)

  • Feifei Ge

    (State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University)

  • Jiangtuan Wang

    (State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University)

  • Xiaofen Li

    (State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University)

  • Meiyu Geng

    (Shanghai Institute of Materia Medica, Chinese Academy of Sciences)

  • Jinheng Wang

    (State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University)

  • Daolin Tang

    (UT Southwestern Medical Center)

  • Jinbao Liu

    (State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University)

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.

Suggested Citation

  • Xi Chen & Xin Chen & Ding Yan & Na Zhang & Wen Fu & Meixuan Wu & Feifei Ge & Jiangtuan Wang & Xiaofen Li & Meiyu Geng & Jinheng Wang & Daolin Tang & Jinbao Liu, 2024. "GV-971 prevents severe acute pancreatitis by remodeling the microbiota-metabolic-immune axis," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52398-z
    DOI: 10.1038/s41467-024-52398-z
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    References listed on IDEAS

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    1. Jiao Liu & Xinxin Song & Feimei Kuang & Qiuhong Zhang & Yangchun Xie & Rui Kang & Guido Kroemer & Daolin Tang, 2021. "NUPR1 is a critical repressor of ferroptosis," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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