| Title: |
A6 INVESTIGATING THE RELATIONSHIP BETWEEN MUCOSAL INFLAMMATION AND PROTEOLYTIC ACTIVITY IN CROHN’S DISEASE |
| Authors: |
Szeto, J; Rueda, G H; Hann, A; Constante, M; Wang, X; Deraison, C; Vergnolle, N; Butcher, J; Stintzi, A; Bercik, P; Galipeau, H; Armstrong, D; Verdu, E |
| Source: |
Journal of the Canadian Association of Gastroenterology ; volume 8, issue Supplement_1, page i3-i3 ; ISSN 2515-2084 2515-2092 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2025 |
| Description: |
Background Dysregulated proteolytic activity (PA) has been detected in intestinal biopsy samples of individuals with inflammatory bowel disease (IBD) compared to healthy controls. It is known that increased microbial fecal PA precedes ulcerative colitis (UC) diagnosis in an at-risk population. Intestinal inflammation in UC is characterized by continuous ulceration, inflammation in Crohn’s disease (CD) is patchy in nature. Sites of inflammation in CD has been associated with altered mucosa-associated microbes and higher permeability, suggesting these could be localized sites of increased microbial PA. Aims To investigate whether inflamed mucosal areas in CD are associated with proteolytic microbiota and increased permeability. Methods CD patients in flare (n=23) were recruited at McMaster University Medical Centre and matched (or paired) biopsies were collected at colonoscopy from inflamed and adjacent (within 5 cm) non-inflamed sites. Biopsy mucosal-to-serosal 51Cr-EDTA flux rate and tissue conductance were measured with Ussing chambers. Total proteolytic (trypsin), elastase-like (FITC-elastin), and mucolytic (0.05% mucin plates) activities were also assessed in biopsies from both sites and in situ zymography was used to measure and localize elastase-like activity in biopsy samples. Mucosal brushing samples from the same participants were also collected and total RNA purified for metatranscriptomic analysis to characterize active microbial pathways with a focus on identifying highly expressed microbial proteases. Results Paracellular permeability and tissue conductance were greater in biopsies from inflamed areas than in biopsies from matched non-inflamed areas (p |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/jcag/gwae059.006 |
| Availability: |
https://doi.org/10.1093/jcag/gwae059.006; https://academic.oup.com/jcag/article-pdf/8/Supplement_1/i3/61814370/gwae059.006.pdf |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.259283F9 |
| Database: |
BASE |