Paneth Cell Ablation Aggravates Pancreatic and Intestinal Injuries in a Rat Model of Acute Necrotizing Pancreatitis after Normal and High-Fat Diet.

Junjie Fan,Yue Zeng,Chunlan Huang,Xinyuan Fu,Yingying Lu,Lungen Lu,Junyuan Zheng,Liyan Liu,Zehua Huang,Qixiang Mei,Yuecheng Guo

doi:10.1155/2019/8474523

Abstract

We previously reported that acute necrotizing pancreatitis (ANP) after normal or high-fat diet is associated with a decreased number of Paneth cells in ileal crypts. Here, we ablated Paneth cells in a rat model of ANP after normal and high-fat diet to investigate the effects on disease symptoms. Adult male Sprague-Dawley rats received standard rat chow or a high-fat diet for 2 weeks, after which they were treated with dithizone to deplete Paneth cells. Six hours later, ANP was established by retrograde injection of sodium taurocholate into the biliopancreatic duct. Rats were sacrificed at 6, 12, and 24 h for assessment. We found dithizone aggravated ANP-associated pathological injuries to the pancreas and ileum in rats on high-fat or standard diets. Lysozyme expression in ileal crypts was decreased, while serum inflammatory cytokines (TNFα, IL-1β, and IL-17A) and intestinal permeability (serum DAO activity and D-lactate) were increased. Expression of tight junction proteins (claudin-1, zo-1, and occludin) was decreased. Using high-throughput 16S rRNA sequencing, we found dithizone reduced microbiota diversity and altered microbiota composition in rats on high-fat or standard diets. Dithizone decreased fecal short-chain fatty acids (SCFAs) in rats on high-fat or standard diets. Changes in intestinal microbiota correlated significantly with SCFAs, lysozyme, DAO activity, D-lactate, inflammatory cytokines, and pathological injury to the pancreas and ileum in rats on high-fat or standard diets. In conclusion, ablation of Paneth cells exacerbates pancreatic and intestinal injuries in ANP after normal and high-fat diet. These symptoms may be related to changes in the intestinal microbiota.

Highlights

Acute necrotizing pancreatitis (ANP) is a severe form of acute pancreatitis characterized by inflammation associated with necrosis in and around the pancreas
We have previously reported that ANP associated with high-fat diet intake is associated with severe systemic inflammation, decreased Paneth cells in ileal crypts, altered microbiota composition, and decreased microbial diversity [4, 5]
Escherichia-Shigella and Enterococcus were negatively associated with short-chain fatty acids (SCFAs) and lysozyme expression, while they positively associated with serum diamine oxidase (DAO), serum D-lactate, serum inflammatory cytokines, and pathological injuries (Figure 6(b))

Summary

Introduction

Acute necrotizing pancreatitis (ANP) is a severe form of acute pancreatitis characterized by inflammation associated with necrosis in and around the pancreas. High-fat diet increases the risk of ANP [1] and can exacerbate ANP inflammation and increase complication rates [2]. We have previously reported that ANP associated with high-fat diet intake is associated with severe systemic inflammation, decreased Paneth cells in ileal crypts, altered microbiota composition, and decreased microbial diversity [4, 5]. A high-fat diet increases serum lipid levels [10] and decreases the number of Paneth cells, which in turn reduces the level of antimicrobial peptides in the intestine and alters microbiota structure [11]. We used dithizone, a chelator of zinc complexes [15], to deplete Paneth cells in rats with ANP after normal and high-fat diet. Effects on intestinal barrier function, microbiota structure, SCFAs, and pancreatic and ileal pathological injuries were examined

Materials and Methods

Results

12 H 24 H

Discussion

Conclusions

Conflicts of Interest