A103 COMBINATORIAL EFFECT OF EARLY LIFE ANTIBIOTIC EXPOSURE AND HIGH-FAT DIET ON COLITIS SUSCEPTIBILITY
Notice bibliographique
Résumé
The etiology of Inflammatory Bowel Disease (IBD) is multifactorial, involving genetics, the immune response, environment and the gut microbiota. Early life antibiotic exposure and a high-fat ‘Western’ diet have both been linked to increased risk of IBD. We hypothesized that genetically susceptible Nod2-deficient mice that received a ‘double hit’ of early life antibiotics and high-fat diet (HFD) throughout life would be more susceptible to colitis. Following birth, Nod2-/- mice were given amoxicillin-supplemented or control water until weaning (day 21). At weaning, mice received either normal diet (ND, 18% kcal from fat) or HFD (45% kcal from fat, Envigo). Stool samples and weights were collected weekly starting at weaning. On days 56–61, 3.5% DSS was administered to induce colitis. Mice were sacrificed and tissues harvested for analysis on day 64. At weaning, mice treated with amoxicillin weighed more than water-treated mice. Water + HFD mice displayed a trend for increased weight gain over time compared to all other groups. As expected, from days 56–61, mice treated with DSS lost weight, however, mice on HFD lost significantly less weight than ND mice. DSS treatment resulted in shortened colon length, but no difference was seen between HFD and ND treatment groups. Interestingly, amoxicillin + HFD treatment resulted in significantly higher fat pad weight than other treatment groups, and while DSS resulted in reduction of fat pad weight, amoxicillin + HFD mice had significantly more fat pad remaining than other DSS treatment groups. Fecal lipocalin-2 (Lcn-2) did not differ between groups at day 56, before colitis induction. Increased Lcn-2 levels were observed in DSS-treated mice, and amoxicillin + HFD mice had increased Lcn-2 compared to water + HFD and amoxicillin + ND mice on day 64. While water + HFD mice displayed greater weight gain trends overall, amoxicillin + HFD mice had greater fat pad weights, in both DSS and non-DSS groups. In contrast to what was hypothesized, HFD prevented dramatic weight changes upon DSS administration. Fecal Lcn-2 levels were increased in amoxicillin + HFD mice following DSS, suggesting that while weight change was reduced, these mice were still experiencing significant inflammation. Together, this indicates that a combination of HFD and early life antibiotics could lead to alterations of the gut microbiota and influence severity of DSS. Analysis of the microbiota in these mice is currently underway. These data reinforce the hypothesis that various environmental factors can have combinatorial effects on colitis susceptibility, possibly via gut microbiota manipulation. This work was supported by a CAG Summer Studentship Award. CAG
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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) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| 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 | 0,001 |
| 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 ».