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Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection
Published on: May 10, 2024
GV-971 prevents severe acute pancreatitis by remodeling the microbiota-metabolic-immune axis
Xi Chen1, Xin Chen1,2, Ding Yan1
1Affiliated Cancer Hospital & Institute of Guangzhou Medical University, Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Disease, State Key Laboratory of Respiratory Disease, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
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.
Insights
The anti-Alzheimer's drug GV-971 shows promise for treating severe acute pancreatitis (SAP). It reshapes gut microbiota, modulates immune responses, and reduces inflammation by targeting key metabolic pathways.
Area of Science:
- Gastroenterology and Immunology
- Microbiome Research
- Pharmacology
Background:
- Severe acute pancreatitis (SAP) is a life-threatening condition with limited therapeutic strategies.
- Existing treatments for SAP are insufficient, highlighting the need for novel interventions.
Purpose of the Study:
- To investigate the potential protective effects of GV-971 (sodium oligomannate), an anti-Alzheimer's drug, in mouse models of severe acute pancreatitis.
- To elucidate the mechanisms underlying GV-971's therapeutic action in SAP, focusing on the gut microbiota and immune system modulation.
Main Methods:
- Utilized male mouse models of severe acute pancreatitis.
- Employed microbiome sequencing, intestinal microbiota transplantation, and mass cytometry to analyze host-microbiota interactions.
- Conducted metabolomics analysis of cecal contents to identify key metabolites.
Main Results:
- GV-971 administration significantly protected against SAP in mouse models.
- GV-971 treatment altered gut microbiota composition, notably increasing Faecalibacterium abundance.
- The drug modulated peripheral and intestinal immune responses and identified short-chain fatty acids (propionate, butyrate) as key mediators inhibiting M1 macrophage polarization via the MAPK pathway.
Conclusions:
- GV-971 demonstrates significant therapeutic potential for severe acute pancreatitis.
- The drug exerts its protective effects by modulating the gut microbiota-metabolic-immune axis.
- These findings position GV-971 as a promising candidate for novel SAP therapies.
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