A265 TEMPORAL DYNAMICS OF SYMPTOMS AND GUT MICROBIOTA IN EPISODES OF IRRITABLE BOWEL SYNDROME
Notice bibliographique
Résumé
Abstract Background Irritable bowel syndrome (IBS) is a disorder of gut-brain axis that manifests with chronic abdominal pain, altered bowel habits, and frequent psychiatric comorbidities. Despite mounting evidence showing gut microbiota composition and associated metabolites being altered in IBS, the mechanisms by which they drive the symptoms are unclear. We have previously shown that several IBS symptoms co-occur, that their severity vary among IBS subtypes (10.1093/jcag/gwab049.050), and that several bacterial taxa are differentially modulated during periods of symptom flares and remission. Here we investigate whether the changes in gut microbiome and bacterial metabolites are linked to symptom occurrence and severity. Purpose To investigate temporal associations of IBS symptoms with gut microbiota profiles and metabolites. Method 16S rRNA gene sequencing was performed on stool samples of 28 IBS patients (IBS-D n=20, IBS-C n=8) and 10 healthy controls (HC), collected weekly over a period of 25 weeks, during which gut and mood symptoms were recorded (total of 950 samples). Correlations between principal ordinates obtained from symptom scores and microbiota beta diversity were studied using Procrustes analysis in R. Metabolomics was performed by Mass Spectrometry and analysed using MetaboAnalyst 5.0. Statistical significance was set at p<0.05. Result(s) Significant correlation was found between the symptom scores and microbiota beta diversity ordinates over time in 7 patients (5 IBS-D and 2 IBS-C subjects) out of 28 IBS patients. Metabolomics performed on samples selected based on Procrustes analysis and symptom severity scores of individual subjects showed that several pathways are altered in IBS patients (both subtypes) compared to HC, including primary bile acid biosynthesis, beta alanine metabolism, pyrimidine and histidine metabolism. Furthermore, during symptom flares, ornithine, citrulline and gluconic acid vary in IBS-D, while amino acids cysteine, methionine, threonine, and glycine vary in IBS-C subjects. Conclusion(s) Our results suggest that IBS symptoms and changes in gut microbiota composition and metabolites must be studied in conjunction, in order to understand the mechanisms underlying IBS pathophysiology. We found that same pathways are altered in IBS subjects irrespective of their subtype, suggestive of a basal metabolic shift in IBS patients. This shift may make them sensitive to further gut microbial modulation of carbohydrate and protein metabolism in IBS-D and IBS-C subjects, respectively, leading to symptom flares. Further analyses are needed to investigate these metabolites and associated bacteria, as they can help identifying subsets of patients with specific disease mechanisms. This will be a steppingstone in moving away from symptom-based subtyping towards mechanism-based grouping and developing effective treatment strategies accordingly. Disclosure of Interest None Declared
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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 | 0,001 |
| 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 | 0,000 | 0,000 |
| 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 ».