A49 TWO NOVEL LIVE BIOTHERAPEUTIC PRODUCTS PROTECT DSS-EXPOSED MICE FROM ACUTE COLITIS WHEN COMPARED TO 5-ASA
Notice bibliographique
Résumé
Abstract Background Live biotherapeutic products (LBPs) offer a more rationalized and multitargeted approach to treating gastrointestinal diseases. BioColoniz and BioPersist are two LBPs derived from the parental strains L. reuteri and E. coli Nissle 1917 (EcN), respectively. The parental strains are known to offer some benefit in preventing relapses in IBD patients however the results are heterogeneous. To overcome this, the parental strains were approached as LBPs by introducing traits to thrive under the inflammatory conditions of the colon. Therefore, our aim is to characterize the role of these LBPs in IBD. Purpose To evaluate the therapeutic effect of the LBPs BioColoniz and BioPersist in an acute model of colitis. Method Female C57Bl/6 mice were treated with BioColoniz or BioPersist via oral gavage for three consecutive days prior to DSS challenge. Then mice were exposed to 3.5% DSS via drinking water for seven days. As controls, we also included mice treated with vehicle or the parental strains L. reuteri or EcN. In order to compare the effect of LBPs in the onset of acute colitis to current maintenance therapies for UC, we also exposed another group of mice to DSS and simultaneously administer 5-ASA. Mice were monitored daily for signs of disease and at the end of the experiment, colon tissue was collected for histopathological and molecular analysis. Result(s) The administration of BioColoniz and BioPersist delayed and decreased the colitic phenotype of mice exposed to DSS. Differences in signs of disease, such as diarrhea and weight loss, were evident by day 4 for vehicle or 5-ASA groups, whereas mice in the LBPs groups were still gaining weight. When analyzing the histopathological changes, mice in the LBPs groups presented lower scores when compared to the vehicle and 5-ASA groups. Specifically, mice treated early with BioColoniz or BioPersist presented a more preserved mucosal architecture with visible crypts. Although 5-ASA-treated mice still had vestiges of crypts, the damage in the mucosal architecture was more severe, similar to the observed in mice treated with the parental strains EcN and L. reuteri. We also looked at the expression of proinflammatory cytokines, finding an increase in TNFα, IFNγ, and IL-17a in mice treated with 5-ASA but not in mice treated with LBPs. However, the expression of protective factors such as mucin Muc2 or the antimicrobial peptide Reg3γ was similarly high in 5-ASA and LBP-treated mice when compared to vehicle or parental strains groups, suggesting some therapeutic commonalities between 5-ASA and our LBPs. Conclusion(s) The early administration of the LBPs BioColoniz and BioPersist protect mice from severe acute colitis, being more protective than 5-ASA. Since some differences and similarities were observed between the LBPs- and 5-ASA-treated mice, such as crypt preservation versus increased expression of some protective factors, the next step will aim to identify which mechanisms are specifically triggered by the LBPs. Disclosure of Interest None Declared
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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 | 0,000 | 0,000 |
| 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 ».