Enteric bacterial proteases in inflammatory bowel diseasepathophysiology and clinical implications

Numerous reports have identified a dysbiosis in the intestinal microbiota in patients suffering from inflammatory bowel diseases(IBD),yet the mechanism(s)in which this complex microbial community initiates or perpetuates inflammation remains unclear.The purpose of this review is to present evidence for one such mechanism that implicates enteric microbial derived proteases in the pathogenesis of IBD.We highlight and discuss studies demonstrating that proteases and protease receptors are abundant in the digestive system.Additionally,we investigate studies demonstrating an association between increased luminal protease activity and activation of protease receptors,ultimately resulting in increased intestinal permeability and exacerbation of colitis in animal models as well as in human IBD.Proteases are essential for the normal functioning of bacteria and in some cases can serve as virulence factors for pathogenic bacteria.Although not classified as traditional virulence factors,proteases originating from commensal enteric bacteria also have a potential association with intestinal inflammation via increased enteric permeability.Reports of increased protease activity in stools from IBD patients support a possible mechanism for a dysbiotic enteric microbiota in IBD.A better understanding of these pathways and characterization of the enteric bacteria involved,their proteases,and protease receptors may pave the way for new therapeutic approaches for these diseases.

Development and validation of a registry-based definition of eosinophilic esophagitis in Denmark

AIM:To develop and validate a case definition of eosinophilic esophagitis(EoE) in the linked Danish health registries.METHODS:For case definition development,we queried the Danish medical registries from 2006-2007 to identify candidate cases of EoE in Northern Denmark.All International Classification of Diseases-10(ICD-10) and prescription codes were obtained,and archived pathology slides were obtained and re-reviewed to determine case status.We used an iterative process to select inclusion/exclusion codes,refine the case definition,and optimize sensitivity and specificity.We then re-queried the registries from 2008-2009 to yield a validation set.The case definition algorithm was applied,and sensitivity and specificity were calculated.RESULTS:Of the 51 and 49 candidate cases identified in both the development and validation sets,21 and 24 had EoE,respectively.Characteristics of EoE cases in the development set [mean age 35 years;76% male;86% dysphagia;103 eosinophils per high-power field(eos/hpf)] were similar to those in the validation set(mean age 42 years;83% male;67% dysphagia;77 eos/hpf).Re-review of archived slides confirmed that the pathology coding for esophageal eosinophilia was correct in greater than 90% of cases.Two registrybased case algorithms based on pathology,ICD-10,and pharmacy codes were successfully generated in the development set,one that was sensitive(90%) and one that was specific(97%).When these algorithms were applied to the validation set,they remained sensitive(88%) and specific(96%).CONCLUSION:Two registry-based definitions,one highly sensitive and one highly specific,were developed and validated for the linked Danish national health databases,making future population-based studies feasible.