Resumen
Background & Aims: The Crohn's disease (CD) exclusion diet (CDED) plus partial enteral nutrition (PEN) and exclusive enteral nutrition (EEN) both induce remission in pediatric 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: A total of 216 fecal metabolites were measured in 80 fecal samples at week (W) 0, W6, and W12, of children with mild to moderate CD in a prospective randomized trial comparing CDED+PEN vs EEN. The metabolites were measured using liquid chromatography coupled to mass spectrometry. Metagenome Kyoto Encyclopedia of Genes and Genomes Orthology analysis was performed to investigate the differential functional gene abundance involved in specific metabolic pathways. Data were analyzed according to clinical outcome of remission (W6_rem), no remission (W6_nr), sustained remission (W12_sr), and nonsustained (W12_nsr) remission. Results: A decrease in kynurenine and succinate synthesis and an increase in N-α-acetyl-arginine characterized CDED+PEN W6_rem, whereas changes in lipid metabolism characterized EEN W6_rem, especially reflected by lower levels in ceramides. In contrast, fecal metabolites in EEN W6_nr were comparable to baseline/W0 samples. CDED+PEN W6_rem children 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 the 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 inflammatory bowel disease–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. Clinicaltrials.gov, Number NCT01728870.
| Idioma original | English |
|---|---|
| Publicación | Gastroenterology |
| DOI | |
| Estado | Accepted/In press - 2022 |
Nota bibliográfica
Funding Information:Funding This study was funded by grants from the Azrieli Foundation and Nestlé Health Science to Arie Levine. Nestlé Health Science also kindly provided Modulen to all participating sites to ensure uniformity of the formula used among participants and provide the formula to enrolled patients for the duration of the study. The conduct of the study in Canada (Halifax, Edmonton) was supported by local divisional funds, a Women and Children’s Health Research Institute Research Capacity Building Award, and a Canadian Institutes of Health Research and New Investigator award (to Johan E. Van Limbergen). The funders of the study had no role in the design of the study, data collection or analysis, interpretation of data, or writing of the report or in the decision to submit the paper for publication. None of the funders had access to the data. This study was also supported by funding from the Wetenschappelijke Advies Raad of Stichting Steun Emma (Emma Children’s Hospital) and the Department of Pediatrics, Amsterdam University Medical Centers. Johan E. Van Limbergen was supported by a Pro-KIIDS Clinical Research Network Award (585718).
Publisher Copyright:
© 2022 The Authors
ASJC Scopus Subject Areas
- Hepatology
- Gastroenterology
PubMed: MeSH publication types
- Journal Article
- Randomized Controlled Trial
- Research Support, Non-U.S. Gov't