LAUSR

BACKGROUND & AIMS Crohn's Disease Exclusion Diet + Partial Enteral Nutrition (CDED+PEN) and exclusive enteral nutrition (EEN) both induce remission in pediatric Crohn's disease (CD). CDED+PEN is better tolerated and able to sustain remission. We characterized the changes in fecal metabolites induced by CDED+PEN and EEN and their relationship with remission. METHODS 216 fecal metabolites were measured in 80 fecal samples at week(W)0, W06 and W12, of children with mild-to-moderate pediatric CD patients in a prospective randomized trial comparing CDED+PEN vs EEN. The metabolites were measured using liquid chromatography coupled to mass spectrometry. Metagenome-KO analysis was performed to investigate the differential functional gene abundance involved in specific metabolic pathways. Data were analyzed according to clinical outcome of remission (W06_rem), no remission (W06_nr), sustained remission (W12_sr) and non-sustained (W12_nsr) remission. RESULTS A decrease in kynurenine and succinate synthesis and an increase in N-α-Acetyl-arginine characterized CDED+PEN W06_rem, while changes in lipid metabolism characterized EEN W06_rem, especially reflected by lower levels in ceramides. In contrast, fecal metabolites in EEN W06_nr were comparable to baseline/W0 samples. CDED+PEN W06_rem maintained metabolome changes through W12. In contrast, W12_nsr children in the EEN group, who resumed a free diet after week 6, did not. The metabolome of CDED+PEN differed from EEN in purine, pyrimidine and sphingolipid pathways. A significant differential abundance in several genes involved in these pathways was detected. CONCLUSION CDED+PEN- and EEN-induced remission are associated with significant changes in IBD-associated metabolites such as kynurenine, ceramides, amino acids and others. Sustained remission with CDED+PEN, but not EEN, was associated with persistent changes in metabolites. ClincialTrials.gov number, NCT01728870.