A6 INVESTIGATING THE RELATIONSHIP BETWEEN MUCOSAL INFLAMMATION AND PROTEOLYTIC ACTIVITY IN CROHN’S DISEASE
Notice bibliographique
Résumé
Abstract 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<0.001). Elastase-like and mucolytic activities were higher in inflamed areas compared to matched non-inflamed areas (p<0.05 and p=0.04, respectively), no significance was detected in total proteolytic activity. In situ zymography revealed greater elastase-like activity in inflamed areas compared to non-inflamed areas (p=0.04), localized to both the epithelial and submucosa layers in inflamed tissues but only to the epithelial layer in matched non-inflamed tissue. Preliminary analysis of the metatranscriptomics results suggests that specific microbial proteases may be increased at inflamed sites in CD. Conclusions Our results suggest that localised variations in tissue inflammation, PA and mucosal permeability in CD may be causally linked, providing a rationale for the patchy distribution of mucosal injury. We, therefore, hypothesize that microbial elastase-like activity promotes mucosal inflammation through barrier disruption. This mechanism could be targeted locally to prevent or modulate microbially associated PA with the aim of enhancing mucosal healing in IBD. Funding Agencies:
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».