Crohn's Disease Exclusion Diet Plus Partial Enteral Nutrition Induces Sustained Remission in a Randomized Controlled Trial

Arie Levine, E. Wine, Amit Assa, R. Sigall Boneh, Ron Shaoul, Michal Kori, Shlomi Cohen, S. Peleg, Hussein Shamaly, Avi On, Peri Millman, Lee Abramas, T. Ziv-Baran, Shannan Grant, G. Abitbol, Katherine A. Dunn, Joseph P. Bielawski, J. Van Limbergen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background & Aims: Exclusive enteral nutrition (EEN) is recommended for children with mild to moderate Crohn's disease (CD), but implementation is challenging. We compared EEN with the CD exclusion diet (CDED), a whole-food diet coupled with partial enteral nutrition (PEN), designed to reduce exposure to dietary components that have adverse effects on the microbiome and intestinal barrier. Methods: We performed a 12-week prospective trial of children with mild to moderate CD. The children were randomly assigned to a group that received CDED plus 50% of calories from formula (Modulen, Nestlé) for 6 weeks (stage 1) followed by CDED with 25% PEN from weeks 7 to 12 (stage 2) (n = 40, group 1) or a group that received EEN for 6 weeks followed by a free diet with 25% PEN from weeks 7 to 12 (n = 38, group 2). Patients were evaluated at baseline and weeks 3, 6, and 12 and laboratory tests were performed; 16S ribosomal RNA gene (V4V5) sequencing was performed on stool samples. The primary endpoint was dietary tolerance. Secondary endpoints were intention to treat (ITT) remission at week 6 (pediatric CD activity index score below 10) and corticosteroid-free ITT sustained remission at week 12. Results: Four patients withdrew from the study because of intolerance by 48 hours, 74 patients (mean age 14.2 ± 2.7 years) were included for remission analysis. The combination of CDED and PEN was tolerated in 39 children (97.5%), whereas EEN was tolerated by 28 children (73.6%) (P = .002; odds ratio for tolerance of CDED and PEN, 13.92; 95% confidence interval [CI] 1.68–115.14). At week 6, 30 (75%) of 40 children given CDED plus PEN were in corticosteroid-free remission vs 20 (59%) of 34 children given EEN (P = .38). At week 12, 28 (75.6%) of 37 children given CDED plus PEN were in corticosteroid-free remission compared with 14 (45.1%) of 31 children given EEN and then PEN (P = .01; odds ratio for remission in children given CDED and PEN, 3.77; CI 1.34–10.59). In children given CDED plus PEN, corticosteroid-free remission was associated with sustained reductions in inflammation (based on serum level of C-reactive protein and fecal level of calprotectin) and fecal Proteobacteria. Conclusion: CDED plus PEN was better tolerated than EEN in children with mild to moderate CD. Both diets were effective in inducing remission by week 6. The combination CDED plus PEN induced sustained remission in a significantly higher proportion of patients than EEN, and produced changes in the fecal microbiome associated with remission. These data support use of CDED plus PEN to induce remission in children with CD. no: NCT01728870.

Original languageEnglish
Pages (from-to)440-450.e8
Issue number2
StatePublished - Aug 2019


FundersFunder number
Canada Research Chair Tier 2 in Translational Microbiomics
Canadian Association of Gastroenterology-Crohn's Colitis Canada
Canadian Association of Gastroenterology-Crohn’s Colitis Canada
Canadian Foundation of Innovation John R. Evans Leadership Fund35235, 36764
Department of Applied Human Nutrition
MacLeod family
Janssen Biotech
Takeda Pharmaceutical Company
Women and Children's Health Research Institute
Nestlé Health Science
Crohn's and Colitis Foundation
Mount Saint Vincent University
Canadian Institutes of Health Research
Nova Scotia Health Research Foundation
GlaxoSmithKline Australia
Azrieli Foundation
Crohn's and Colitis Canada


    • Crohn's Disease
    • Inflammatory Bowel Disease
    • Microbiome
    • Treatment


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