Mucosal Thrombin Alters Gut Microbiota Biofilms Structure And Promote Dispersion Of Bacteria With Aggressive Behavior
Notice bibliographique
Résumé
Alterations of gut microbiota have been implicated in a broad variety of intestinal diseases. The mechanisms whereby this may occur remains elusive. Gut mucosal microbiota is naturally organized as a polymicrobial biofilm, separated from the intestinal epithelium by a sterile mucus layer. We recently discovered that intestinal epithelium releases active thrombin, which plays a key role in segregation of intestinal biofilms from host tissue. Furthermore, we detected an upregulation of active thrombin in inflamed human patients and in models of colitis. Objectives Our study objective was to determine whether exposure to high thrombin, such as this occurring during inflammation, will alter commensal microbiota biofilms and promote the dispersion of bacteria predisposed to damage the intestinal epithelium. Methods Microbiota extracted from healthy human colon biopsies were seeded into the Calgary Biofilm Device and polystyrene coupons to develop, a multispecies anaerobic biofilm. Biofilms were exposed to various concentrations of thrombin (10 to 1000 Unit/ml). Dispersed bacteria released from thrombin‐treated biofilms were collected and their composition was assessed by 16S sequencing. These bacteria were apically exposed to human epithelial monolayers on transwells (Caco2 and HT29MTX). Adhesion (90 minutes), invasion (gentamicin assay, 3 hours) and translocation (4 hours) to basolateral side was quantified by plating on agar. Transwells were processed for fluorescent in situ hybridization for bacteria staining and phalloidin antibody for host cell cytoskeleton. Motility phenotype of biofilmdispersed bacteria was assessed on soft agarose gels (swarming and swimming). Mice (B6) were treated intracolonically with thrombin (5U per day for 10 days) or boiled thrombin (similar dose). Rats (Wistar) were treated with TNBS to induce colitis, and were treated for 3 days intracolonically with dabigatran (thrombin inhibitor, 1 μg/kg) or vehicle. Results Biofilm‐dispersed bacteria from thrombin‐treated biofilms attached more importantly to the epithelial monolayers compared to untreated biofilm. 3D reconstruction images confirmed such thrombin‐induced phenotype. Thrombin alters swarming and swimming motility in soft agarose gel. 16S analysis further precise the specific composition of biofilm‐dispersed bacteria after thrombin exposure. In mice, intrarectal administration of thrombin caused alterations of gut microbiota biofilms structure (16S sequencing) and organization ( in situ imaging of gut microbiota). During colitis in rats, local inhibition of thrombin activity prevented gut microbiota biofilms alterations associated with colitis (in situ imaging of gut microbiota and 16S analysis). Conclusions These data suggest that high concentration of thrombin released at gut mucosal surface during inflammation alters gut biofilm organization and modifies the phenotype of biofilm‐dispersed bacteria, which were able to invade and cross the epithelial barrier, thus increasing their likelihood to trigger inflammatory flares.
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 | 0,000 | 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 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».