A94 SHIP-MICROBIOME INTERACTIONS IN INTESTINAL INFLAMMATION
Notice bibliographique
Résumé
Immune regulating Src homology domain 2-containing inositol phosphatase (SHIP) protein levels and activity are reduced in patients with the chronic intestinal inflammatory condition, Crohn’s disease (CD). SHIP deficient (-/-) mice develop spontaneous CD-like ileal inflammation beginning at 4 weeks of age. Several groups have associated the microbiome with the pathogenesis of CD, where the loss of other immune regulating genes such as NLRP6, NLRP12, and NOD2 result in microbial population changes and intestinal inflammation in mice. However, the microbiome of SHIP-/- mice has not been examined. To investigate whether SHIP attenuates ileal inflammation by maintaining microbial diversity and protective commensal populations. Bacterial DNA was extracted from stool and colonic, cecal, and ileal contents of SHIP-/- and SHIP+/+ mice at 4 and 8 weeks of age. Bacterial load was quantified by qPCR and normalized by 16S rrn gene copy number. V4-V5 hypervariable regions of the 16S rRNA gene were sequenced with the Illumina MiSeq platform and fastq files were imputed using QIIME 1.9. Microbial diversity metrics and relative abundance measures were generated with data rarefied to 5500 sequences per sample. Abundance measures were normalized by rrn gene copy count. Metabolomic data were obtained by PICRUSt v1.1.1 and directly measuring short chain fatty acid concentrations of ileal contents using gas chromatography. Bacterial DNA was extracted from a total of 94 samples. No significant differences were observed in bacterial loads between age and genotype groups, indicating that ileal inflammation in SHIP-/- mice is not associated with bacterial overgrowth. Reductions in microbial alpha-diversity were seen in 8 week old SHIP-/- microbiomes as measured by number of OTUs and chao1. Separation of clusters were seen between 8 week old SHIP-/- and SHIP+/+ during principle component analysis, but not at 4 weeks old. 8 week old SHIP-/- microbiota showed reductions in the unclassified Bacteroidetes family S24-7. Non-significant changes in abundances were seen at the genus-level. Reduced amino acid metabolism and elevated glutathione and lipid metabolism in 8 week SHIP-/- samples were predicted with PICRUSt, consistent with other models of intestinal inflammation. Modest reductions in butyric acid and propionic acid and elevations in branched chain fatty acids were found after the onset of inflammation. Significant changes in bacterial diversity, populations, and metabolism were only observed after the onset of inflammation. Similar but non-significant changes to the microbiome were observed prior to the onset of inflammation. Taken together, these results suggest that SHIP deficiency is sufficient to drive changes in the intestinal microbiome, which may contribute to, and are amplified by intestinal inflammation. CIHR
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 | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,007 | 0,001 |
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 ».