Enteric bacterial proteases in inflammatory bowel diseasepathophysiology and clinical implications

Ian M. Carroll, Nitsan Maharshak*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

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 WJG 20th Anniversary Special Issues (3): Inflammatory bowel disease 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.

Original languageEnglish
Pages (from-to)7531-7543
Number of pages13
JournalWorld Journal of Gastroenterology
Volume19
Issue number43
DOIs
StatePublished - 2013
Externally publishedYes

Funding

FundersFunder number
National Institute of Diabetes and Digestive and Kidney DiseasesK01DK092330

    Keywords

    • Enteric microbiota
    • Epithelial barrier
    • Protease
    • Protease associated receptor
    • Proteinase

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