Combinatory antibiotic treatment protects against experimental acute pancreatitis by suppressing gut bacterial translocation to pancreas and inhibiting NLRP3 inflammasome pathway. Issue 1 (January 2020)

• Record Type: Journal Article
• Authors: Jia, Lingling; Chen, Hao; Yang, Jun; Fang, Xin; Niu, Wenying; Zhang, Ming; Li, Jiahong; Pan, Xiaohua; Ren, Zhengnan; Sun, Jia; Pan, Li-Long
• Other Names: Vogel Stefanie guest-editor.
• Is Part Of: Innate immunity. Volume 26:Issue 1(2020:Jan.)
• Page Start: 48
• Page End: 61
• Publication Date: 2020-01
• Subjects: Gut bacterial translocation -- antibiotic -- gut barrier -- acute pancreatitis -- Toll-like receptor 4; Natural immunity -- Periodicals; Endotoxins -- Periodicals; 616.07905
• DOI: 10.1177/1753425919881502
• Languages: English
• ISSNs: 1753-4259

Abstract

Gut bacterial translocation following impaired gut barrier is a critical determinant of initiating and aggravating acute pancreatitis (AP). Antibiotic combination (ABX; vancomycin, neomycin and polymyxin b) is capable of reducing gut bacteria, but its efficacy in AP prevention and the underlying mechanism have not been investigated yet. AP was induced in BALB/c mice by caerulein (CAE) hyperstimulation. We found that ABX supplementation attenuated the severity of AP as evidenced by reduced pancreatic oedema and myeloperoxidase activity. The protective effect was also confirmed by improved histological morphology of the pancreas and decreased pro-inflammatory markers (IL-1β, TNF-α, MCP-1) in pancreas. ABX administration inhibits the activation of colonic TLR4/NLRP3 inflammasome pathway. Subsequently, down-regulated NLRP3 resulted in decreased colonic pro-inflammation (IL-1β, IL-6, MCP-1) and enhanced gut physical barrier as evidenced by up-regulation of tight junction proteins including occludin, claudin-1 and ZO-1, as well as improved histological morphology of the colon. Together, combinatory ABX therapy inhibited the translocation of gut bacteria to pancreas and its amplification effects on pancreatic inflammation by inhibiting the pancreatic NLRP3 pathway, and inhibiting intestinal-pancreatic inflammatory responses. The current study provides the basis for potential clinical application of ABX in AP.