A43 β-DEFENSINS AS MARKERS OF INTESTINAL DYSBIOSIS: THE NATURE OF CHANGES IN β-DEFENSINS IS DEPENDENT ON THE PROCESS UNDERLYING THE INDUCTION OF DYSBIOSIS
Notice bibliographique
Résumé
Abstract Background Dysbiosis may be defined as a change in the microbial composition or function that results in altered host function. Defensins are antimicrobial peptides, are part of innate immunity, and are important in host defense and maintaining homeostasis. Dysbiosis is a putative mechanism underlying the expression of many functional GI disorders like Irritable Bowel Syndrome (IBS) for which no biomarkers exist. Previous studies have revealed increased β-defensin (β-Def) levels in IBS patients, most likely due to changes in the microbiota. Aims We examined the hypotheses that: 1) Changes in β-Def are dependent on the manner in which dysbiosis is induced, and that 2) the direction of the change in β-Def depends on how dysbiosis was induced. Methods We used 4 models of experimentally induced dysbiosis to determine changes in fecal β-Def and to characterize the microbiota composition before and during the induction of dysbiosis. We used: 1) an antimicrobial cocktail (AC) in water; 2) a high-fat/ high-sugar diet (HFHSD); 3) a high salt diet (HSD) that we previously showed to induce a pro-inflammatory microbiota; and 4) mild restraint stress (MRS). All studies were performed in C57/BL6 mice except studies using MRS that were performed in NIH Swiss mice. In the AC or dietary studies, we employed a one-week intervention preceded by one-week baseline and recovery periods. In MRS studies, mice comparisons were made between a control and a stressed group. Stool samples were collected every 24 hours and were assayed for fecal β-Def levels analysis by an ELISA and microbial composition by 16S gene profiling. Results Exposure to AC or dietary change, but not MRS, resulted in significant decreases in fecal β-Def. Additionally, bacterial composition and diversity profiles were different in all mice except MRS mice (control vs. MRS males: p=0.414; control vs. MRS females: p=0.96). In contrast, mice exposed to the HSD revealed a significant increase in β-Def during treatment compared to baseline in both males (p=0.025) and females (p= 0.0019). The AC mice showed the largest changes and significant correlations between changes in β-Def levels and bacterial diversity (males: p=0.013, r=0.6; females: p=0.007, r=0.6) and richness (males: p=0.0008, r=0.70; females: p=0.003, r=0.62). However, no significant correlations were found between specific bacteria and β-Def levels in the HFHSD group. Conclusions We conclude that directional changes in fecal β-Def levels are dependent on the manner in which dysbiosis is induced. The use of β-Def as a biomarker requires comparisons with baseline levels obtained during remission in order to identify dysbiosis presence in microbiota-associated chronic GI conditions like IBS. Such an approach will identify patient subgroups that may benefit from microbiota-directed therapies. Funding Agencies CIHR
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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 | 0,001 | 0,001 |
| 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 | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».