P1207 Microbiome composition determines sustained remission after the Crohn’s Disease Exclusion Diet (CDED) with or without Partial Enteral Nutrition in adults with mild-moderate Crohn’s disease; Results from the CDED-AD Pilot Randomized Controlled Trial
Authors: Sigall-Boneh R , Organ S , Yanai H , Maharshak N , Dotan I , Abramas L , Wine E , Widesma N , Gu H , Bielawski J , Dunn K , Van Limbergen J 
Published: January 2024

Abstract

Background
The Crohn's Disease (CD) Exclusion Diet (CDED) is an established dietary therapy for children with active mild-to-moderate CD. A recent randomized controlled trial showed efficacy in mild-to-moderate CD in adults. We have previously demonstrated the impact of CDED on the microbiome of children. The aim of this work was to assess if we can determine sustained clinical remission (SCR) from the baseline microbiome composition and examine the effect of CDED on microbiome composition in adult CD.

Methods
This was an open-label, prospective, randomized, controlled pilot trial involving patients with mild-to-moderate CD and evidence of active inflammation. Patients were randomly assigned to receive CDED with partial Enteral Nutrition (PEN) or CDED alone, both for 24 weeks. The V4V5 region of the 16S rRNA gene was amplified and sequenced, and reads were processed using QIIME2 and the SILVA database. Relationships between the microbiome, SCR, and Fecal Calprotectin (FC) were analyzed using logistic regression, Poisson Principal Component Analysis, paired T-Tests and subsampling ranking forward selection.

Results
Clinical remission (CR) at weeks 6, 12 and 24 was achieved in 62.5%, 52.5%, and 50% of patients, respectively. Week 0, 6, 12 and 24 stool samples were available for 35,32,30 and 26 patients, respectively. In patients with SCR, defined as remission at both weeks 12 and 24, the baseline microbiome revealed lower alpha diversity compared to those without SCR (p=0.018), and differing Microbiome principal components (PC) scores (p &lt; 0.01). PC1 and PC3, characterized mainly by Alistipes, Faecalibacterium and UCG-002 predicted SCR (P&lt;0.01). PC2 predicted elevated FC&gt;250 µg/g at week 12 (p=0.004). Baseline abundance of Haemophilus was associated with decreased SCR probability (p&lt;0.01). At week 6 in the entire cohort, there was a significant decrease in Actinobacteriota (p=0.035) and a significant increase in Bacteroidota (p=0.003). Additionally, there was a significant increase in several genera, including beneficial Alistipes and Oscillibacter (p&lt;0.02) in those who achieved CR after 6, 12, or 24 weeks. Higher Firmicutes at week 6 were associated with FC&lt;250 at week 12 (p=0.031). An uncultured genus from the Oscillospiraceae family was significantly associated with a decrease in the probability of SCR (p&lt;0.01) and was significantly increased at week 6 in patients who did not attain CR (p&lt;0.05).

Conclusion
The baseline microbiome composition was associated with SCR and FC&lt;250 at week 12 in adult patients treated with CDED (with or without PEN) over 24 weeks. This suggests that the microbiome could be useful tool to identify patients who would benefit from long-term dietary intervention.