P346 Small bowel permeability improves with nutritional therapy in mild-to-moderate active paediatric Crohn’s disease
Bibliographic record
Abstract
Intestinal permeability (IP) is increased in Crohn’s disease (CD) patients and their first degree relatives. The causes of barrier disruption remain unclear but likely relate to inflammation with possible effects of nutrients and microbes. Infliximab has been shown to improve IP in CD but the impact of nutritional therapy on IP is unknown. We prospectively assessed the effects of nutritional therapy on IP in a randomised controlled trial, comparing the Crohn’s disease exclusion diet (CDED) to the gold standard exclusive enteral nutrition (EEN) in children with CD. Mannitol is an easily absorbed small sugar that reflects the small bowel (SB) surface area, whereas the disaccharide lactulose is only absorbed through larger pores and reflects permeability; therefore, the ratio of lactulose/mannitol (L/M) represents SB relative permeability. The CDED study was a 12-week prospective, international, multi-centre, randomised controlled trial in children with mild-to-moderate active luminal CD, comparing CDED to EEN. During the first 6 weeks of the study patients in the CDED group received CDED Stage 1 diet + 50% calories from liquid formula (Modulen, Nestle) whereas the EEN group were fed exclusively with Modulen. A L/M test for intestinal permeability was performed at weeks 0 and 3 by administering a sugar solution containing lactulose (5 g) and mannitol (1 g) and then collecting urine for LC-MS/MS analysis. A cut-off L/M ratio of 0.015 was chosen, based on published literature (McOmber et al. JPGN 2010). L/M ratios were available at both time points for 39 patients (23 CDED and 16 EEN). At baseline, 9/23 (39%) CDED and 8/16 (50%) EEN patients had a normal L/M ratio, whereas at 3 weeks of treatment this increased to 15/23 (65%) and 9/16 (56%), respectively. Using generalised estimating equation analysis there was no difference in change of L/M between groups (p = 0.193). In both groups, 50% of those with abnormal L/M ratio at baseline (ratio > 0.015) normalised at Week 3 (7/14 for CDED; 4/8 with EEN). Interestingly, 1/14 (7%) CDED cases with normal L/M ratio became abnormal at 3 weeks, vs. 3/16 (19%) in the EEN group (NS). These findings indicate an improvement in IP with 3 weeks of nutritional therapy; however, there was no correlation between change in IP status and failure to respond to therapy or poor compliance to the diet at 3 weeks. Although both EEN and CDED are associated with improved IP, this was not observed in all patients, despite clinical improvement. This suggests that small bowel IP alone may not be a primary mechanism for early clinical response; the effect of IP on sustaining remission following dietary therapy will require further study.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".