P354 Tryptophan metabolites as predictive biomarkers for dietary therapy outcomes in paediatric Crohn's disease
Bibliographic record
Abstract
Abstract Background Crohn's disease (CD) exclusion diet combined with partial enteral nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) are effective in inducing remission in mild-to-moderate paediatric CD. While tolerance is higher with CDED+PEN than with EEN, a subset of patients still does not achieve remission. Diet-induced remission at week 6 was associated with changes in tryptophan (Trp) metabolism.1 Our aim was to investigate whether baseline Trp metabolites could predict dietary therapy outcomes in paediatric CD. Methods In total, 26 mild-to-moderate treatment-naive paediatric CD patients from a prior randomized controlled trial 2, were classified as having remission 6 (R, n =19 (CDED+PEN=10 and EEN=9)) and No-Remission (NR, n=7 (CDED+PEN=3 and EEN=4)) following 6 weeks of CDED+PEN or EEN therapy, based on the Paediatric Crohn’s Disease Activity Index (PDCAI) score (≤10 remission, >10 no remission). We performed targeted quantitative analysis of 21 tryptophan metabolites in baseline faecal samples from both groups, utilizing liquid chromatography coupled with quadrupole mass spectrometry. Receiving Operator Characteristic Curve (ROC) and Random Forest Analysis were used to assess the predictive power of Trp metabolites for dietary outcomes. Results Baseline clinical characteristics were comparable between R and NR. Baseline fecal kynurenine was significantly higher in NR compared to R for CDED+PEN (p=0.02) (Fig 1A) and EEN (p=0.04) (Fig 2A). ROC analysis highlighted the robust predictive power of kynurenine for CDED+PEN (area under the curve (AUC)=0.97) (Fig 1B) and EEN (AUC=0.88) (Fig 2B) induced remission. Random Forest analysis corroborated these observations. Ratios of Trp metabolites were compared to investigate different downstream Trp pathways. The ratio serotonin/kynurenine was the strongest predictor of CDED+PEN-induced remission (AUC=1) (Fig 1C). The ratio 5-OH-Tryptophan/kynurenine (AUC=0.88) (Fig 2C) predicted EEN-induced remission. When data from CDED+PEN and EEN were combined, kynurenine (AUC=0.91) and the ratios of quinolinic acid/kynurenine (AUC=0.93) and kynurenine/indole-3-acetic acid (AUC=0.88) demonstrated strong predictive performance for dietary therapy in general (Fig 3A,B and C). Conclusion Baseline faecal kynurenine has potential as a prognostic biomarker for dietary therapies. Trp metabolite ratios, notably serotonin/kynurenine for CDED+PEN and 5-OH-tryptophan/kynurenine for EEN, showed promising predictive capabilities. If confirmed in validation studies, baseline faecal Trp markers may be able to provide much needed guidance to personalize dietary intervention within the management of paediatric CD. References 1. Gastroenterology. 2022 Oct;163(4):922-936. 2. Gastroenterology. 2019 Aug;157(2):440-450.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".