P1323 Differential Microbiome Responses to the Crohn’s Disease Exclusion Diet in Pediatric vs. Adult Populations: Insights from Randomized Controlled Trials
Authors: Sigall-Boneh R , Organ S , Yanai H , Maharshak N , Dotan I , Abramas L , Wine E , Wierdsma N , Verburgt C , Ghiboub M , Gu H , Bielawski J , Dunn K , Van Limbergen J 
Published: January 2025

Abstract

Background
The Crohn’s Disease (CD) Exclusion Diet (CDED) is a recognized dietary therapy for managing mild-to-moderate CD in children and adults1,2. This study aimed to compare the effects of CDED on the microbiome in children and adults, based on randomized controlled trials (RCTs) in both cohorts1,2.

Methods
We analyzed fecal samples from 2 RCTs; one comparing CDED to exclusive enteral nutrition in children over 12 weeks (n:W0 = 69, n:W06 = 57, n:W12 = 52), and the other examining CDED with or without partial enteral nutrition in adults over 24 weeks (n:W0 = 35, n:W06 = 32, n;W12 = 30, n:W24 = 26). We compared the pediatric CDED group with both adult groups, all with mild-to-moderate disease and active inflammation. The V4-V5 region of the 16S rRNA gene was amplified and sequenced, with reads processed through QIIME2 and the SILVA database. Associations between the microbiome, short-term clinical remission and fecal calprotectin (FC) were analyzed using logistic regression, Poisson Principal Component Analysis, Wilcoxon tests, ANOVA, and subsampling ranking forward selection.

Results
Pediatric patients had higher baseline alpha diversity, which significantly increased by week 12 and was higher in remission compared to adults, who showed a similar but nonsignificant trend. In both pediatric and adult cohorts, baseline Haemophilus abundance was significantly associated with reduced probability of sustained remission (measured at weeks 6 and 12 [pediatric], and 12 and 24 [adults]). Ruminococcus levels increased from baseline to week 6 in patients who did not achieve remission across both cohorts. At week 12, pediatric patients had more taxa associated with achieving remission, whereas adults showed more taxa linked to non-remission. Prevotella was associated with non-remission in both pediatric and adult cohorts, while Akkermansia was linked to non-remission in adults only. By weeks 6 and 12, both cohorts showed increases in Oscillibacter and decreases in Haemophilus.In adults, Alistipes increased over time and was associated with milder disease at baseline for both cohorts. Higher baseline FC in children suggested more severe initial disease. An increase in Firmicutes was associated with lower FC in both cohorts, indicating beneficial microbiome shift in response to CDED. In patients with more severe disease, higher Proteobacteria prevalence was observed, with a stronger difference observed in pediatric than in adult.

Conclusion
These finding suggest that key microbiome could serve as biomarkers for predicting responses to CDED, enabling more personalized dietary management for CD. Microbial shifts associated with reduced inflammation after CDED, highlight the potential for tailored dietary approaches for both children and adults.

References
1.Levine A, Wine E, Assa A et al. Crohn’s Disease Exclusion Diet Plus Partial Enteral Nutrition Induces Sustained Remission in a Randomized Controlled Trial. Gastroenterology. 2019 Aug;157(2):440-450.e8. doi: 10.1053/j.gastro.2019.04.021.
2.Yanai H, Levine A, Hirsch A et al. The Crohn’s disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn’s disease (CDED-AD): an open-label, pilot, randomised trial. Lancet Gastroenterol Hepatol. 2022 Jan;7(1):49-59. doi: 10.1016/S2468-1253(21)00299-5.