Dysbiosis of Intestinal Microbiota and Decreased Antimicrobial Peptide Level in Paneth Cells during Hypertriglyceridemia-Related Acute Necrotizing Pancreatitis in Rats

作者：Chunlan Huang, Jing Chen, Jingjing Wang, Hui Zhou, Yingying Lu, Lihong Lou, Junyuan Zheng, Ling Tian, Xingpeng Wang, Zhongwei Cao, Yue Zeng · 发表于：Frontiers in Microbiology · 年份：2017 · DOI：10.3389/fmicb.2017.00776 · 被引用次数：124 · 研究领域：Pancreatitis Pathology and Treatment、Gastrointestinal motility and disorders、Diabetes and associated disorders

Hypertriglyceridemia (HTG) aggravates the course of acute pancreatitis (AP). Intestinal barrier dysfunction is implicated in the pathogenesis of AP during which dysbiosis of intestinal microbiota contributes to the dysfunction in intestinal barrier. However, few studies focus on the changes in intestine during HTG-related acute necrotizing pancreatitis (ANP). Here, we investigated the changes in intestinal microbiota and Paneth cell antimicrobial peptides (AMPs) in HTG-related ANP in rats. Rats fed a high-fat diet to induce HTG and ANP was induced by retrograde injection of 3.5% sodium taurocholate into biliopancreatic duct. Rats were sacrificed at 24h and 48h, respectively. Pancreatic and ileal injuries were evaluated by histological scores. Intestinal barrier function was assessed by plasma diamine oxidase activity (DAO) and D-lactate level. Systemic and intestinal inflammation was evaluated by TNFα, IL-1β and IL-17A expression. 16S rRNA high throughput sequencing was used to investigate changes in intestinal microbiota diversity and structure. AMPs (α-defensin5 and lysozyme) expression was measured by real-time PCR and immunofluorescence. The results showed that compared with those of normal-lipid ANP (NANP) groups, the HTG-related ANP (HANP) groups had more severe histopathological injuries in pancreas and distal ileum, aggravated intestinal barrier dysfunction and increased TNFα, IL-1β and IL-17A expression in plasma and distal ileum. Principal component analysis (PCA) s...