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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
Dysbiosis of intestinal microbiota and decrease in paneth cell antimicrobial peptide level during acute necrotizing
Jing Chen1, Chunlan Huang1, Jingjing Wang2
1Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Acute necrotizing pancreatitis (ANP) in rats caused intestinal barrier dysfunction and altered gut microbiota. Decreased Paneth cell antimicrobial peptides, like lysozyme, were observed, suggesting their role in ANP pathogenesis.
Area of Science:
- Gastroenterology
- Microbiology
- Pathology
Background:
- Intestinal barrier dysfunction is a key factor in acute necrotizing pancreatitis (ANP).
- Intestinal microbiota dysbiosis contributes to intestinal barrier failure.
- Paneth cells are crucial for maintaining the intestinal barrier and are linked to the gut microbiota.
Purpose of the Study:
- To investigate the alterations in intestinal microbiota composition.
- To examine the changes in Paneth cell antimicrobial peptides (lysozyme and α-defensin5) in the ileum during ANP.
- To explore the relationship between gut dysbiosis and Paneth cell function in ANP.
Main Methods:
- Establishment of ANP in rats via sodium taurocholate injection.
- Histopathological scoring of pancreas and ileum injuries.
- Assessment of intestinal barrier function using plasma diamine oxidase (DAO) and D-lactate levels.
- Measurement of systemic and intestinal inflammation (TNFα, IL-1β, IL-17A).
- 16S rRNA sequencing for fecal microbiota analysis.
- Real-time PCR, western blot, and immunofluorescence for lysozyme and α-defensin5 expression.
Main Results:
- ANP rats exhibited severe pancreatic and ileal injuries, impaired intestinal barrier function, and elevated inflammatory markers compared to sham-operated controls.
- 16S rRNA sequencing revealed decreased microbial diversity and significant dysbiosis in ANP rats, with notable changes at phylum (decreased Saccharibacteria, Tenericutes) and genus levels (increased Escherichia-Shigella, Phascolarctobacterium; decreased others).
- Significant reductions in lysozyme and α-defensin5 mRNA and protein expression were observed in ANP rats, with lysozyme levels inversely correlating with the abundance of Escherichia-Shigella.
Conclusions:
- Intestinal microbiota disorder and reduced Paneth cell antimicrobial peptides are implicated in the pathogenesis of intestinal barrier dysfunction during ANP.
- These findings highlight the intricate interplay between gut microbiota, Paneth cell function, and intestinal barrier integrity in ANP.
- Targeting microbiota modulation and Paneth cell function may offer therapeutic strategies for ANP.
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