A189 ELUCIDATING THE MECHANISTIC ROLE OF GLP-1R IN THE INFLAMMATORY RESPONSE OF MACROPHAGES AND B CELLS TO DIETARY FIBRES
Notice bibliographique
Résumé
Abstract Background Both diet and the microbiome have been implicated in the pathogenesis of inflammatory bowel diseases (IBD). Fibre is not digested; it is fermented by microbes in the large bowel. High fibre intake is related to lower risk for the development of IBD, and a high fibre diet is usually recommended for individuals with IBD. However, work in our lab suggests that select dietary fibres may be pro-inflammatory in a pediatric IBD cohort. Importantly, large bowel dysbiosis in IBD could limit the fermentation of dietary fibres, leading to reduced production of beneficial microbiome metabolites as well as an accumulation of intact fibre in the large bowel. These intact fibres may then interact with immune cells residing in the large bowel, through specific receptors, and perpetuate the inflammatory state seen in IBD. Aims Based on preliminary findings, we hypothesize that the dietary fibre oligofructose acts through GLP-1R on macrophages and B-cells to regulate the inflammatory environment. We expect to find changes in the expression of cytokines and chemokines, and their receptors. Methods Changes in immune cell secretions (ELISA) and the expression of selected inflammatory markers (RT-qPCR) were measured to determine potential pathways involved in response to dietary fibres in vitro. Knockdown of proteins of interest (siRNA) was performed to validate the involvement of these pathways in the inflammatory response to dietary fibres. Cells were treated with oligofructose, oligofructose pre-fermented by bacteria, or no fibre. The involvement of the fibre receptor, GLP-1R, was investigated to understand its connection to pathways identified. Results Qiagen RT2 profiler array (human inflammatory cytokines and receptors) and cytokine secretion (ELISA) indicated that in response to oligofructose macrophages have a predominantly pro-inflammatory response while B cells have an anti-inflammatory response. Presence of GLP-1R in large bowel and terminal ileum biopsies collected during endoscopy was higher in IBD (Crohn disease n=7; Ulcerative colitis n=7) than non-IBD patients (n=7), and expression was confirmed on both B-cells and macrophages. Knockdown of GLP-1R (siRNA) significantly reduced the pro-inflammatory response (IL-1β ELISA) with oligofructose application in THP-1 macrophage cells Conclusions Improving our understanding of the mechanistic link between dietary fibres and immune response will aid us in developing a model for the interactions of oligofructose with the GLP-1R in B cells and macrophages. Findings from this study may be able to inform dietary interventions, prebiotic/probiotic administration, and drug development for treatment of IBDs. Funding Agencies CIHRWeston Foundation
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 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) | 0,000 | 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 tête enseignante, 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 ».