Establishment of a novel extracorporeal bowel model to study luminal approaches to treat inflammatory bowel disease

Abstract

SUMMARYWe have established an extracorporeal bowel model system for the analysis of early events in inflammatory bowel disease (IBD) and therapeutic applications. This model consists of an intestinal segment that is cannulated and perfused in situ, allowing the investigation of cellular responses of apical mucosa cells on luminal applied substances. Short-term treatment with iodoacetamide mimicked experimental intestinal inflammation in IBD, as indicated by histological alterations such as hemorrhage, hyperemia and loss of regular crypt architecture, as well as enhanced expression of cytokines (e.g. IL-6, IL-10 and MCP-1) compared with control segments perfused with media. Perfusion of therapeutic agents (e.g. dexamethasone or Mutaflor) in the small intestine segment significantly reduced the features of early inflammation that are induced by iodoacetamide. Moreover, similar data were obtained for Resormin®, a montmorillonite-illite mixed-layer mineral (smectite), indicating that smectites might be a newly identified therapeutic option for IBD. In summary, this model could provide novel insights into epithelial injury as well as genesis of IBD and, therefore, be useful in testing the therapeutic potential of compounds for IBD therapy.

Smectite as a Preventive Oral Treatment to Reduce Clinical Symptoms of DSS Induced Colitis in Balb/c Mice

“…However, it failed to prevent shortening of the colon. These data correspond with the findings in our previous studies, where the application of a diosmectite also decreased histological alteration and improved the overall histological score [13]. Another animal study from González et al, which used a TNBS colitis model in rats, showed that the diosmectite treatment resulted in amelioration of the intestinal morphological signs and reduced the severity of diarrhea [11].…”

“…We found positive effects on the clinical symptoms associated with DSS-colitis, such as weight loss, stool consistency and occult blood. Furthermore, the positive impact of diosmectite on the histological score, as observed in a previous in vivo study, could be confirmed [13]. Analysis of the gut microbiota composition identified a possible microbiome shaping potential.…”

“…We previously studied the therapeutic potential of a specific natural silicate from Friedland (Germany) on iodoacetamide-induced inflammation in a defined bowel segment of rats. Particularly, histological examinations of intestine, cytokine expression and cell infiltration into intestine segments in a short-term inflammation model revealed beneficial effects of the administered smectite [13]. However, since the mineral was applied therapeutically and within a short-term inflammation model the effects of this smectite in a long-term, well-establish experimental colitis model are still unknown.…”

Heat stress induced gut microbiota changes activate TLR4 / NF-κB signaling pathway contributing to inflammatory bowel disease in pigs

“…Moreover, the TLR4/NF-κB signaling pathway was activated in both the H7 and H14 mice. Breitruck et al [59] reported that the intestinal mucosal structure is damaged in mice with IBD. This injury is characterized by severe bleeding and IL-6 and IL-10 upregulation.…”