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

Abstract

See Covering the Cover synopsis on 269. See editorial on page 295. 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 ¼ 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 ¼ 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 ¼ .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 ¼ .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 ¼ .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

Inducing remission in paediatric Crohn’s disease using nutritional therapies – A systematic review

“…A newly published RCT (July 2019) by the same research group adds further support to use of this novel nutritional therapy. Levine et al . demonstrate that, although there was no significant difference in the number of patients entering remission by week 6, the CDED with PEN ( n = 40) was better tolerated than EEN ( n = 34), with a significantly lower dropout rate.…”

“…demonstrate that, although there was no significant difference in the number of patients entering remission by week 6, the CDED with PEN ( n = 40) was better tolerated than EEN ( n = 34), with a significantly lower dropout rate. It was also suggested that the CDED could be superior to EEN in terms of sustaining remission, with a significantly greater proportion of the CDED group having a PCDAI <10 at week 12 compared to the EEN . Alternative dietary treatment options to EEN are certainly a growing area of interest, with another research team having also recently published their findings after examining a completely solid food‐based diet as opposed to PEN alongside a specialised diet.…”

“…A newly published RCT (July 2019) by the same research group adds further support to use of this novel nutritional therapy. Levine et al (66) demonstrate that, although there was no significant difference in the number of patients entering remission by week 6, the CDED with PEN (n = 40) was better tolerated than EEN (n = 34), with a significantly lower dropout rate. It was also suggested that the CDED could be superior to EEN in terms of sustaining remission, with a significantly greater proportion of the CDED group having a PCDAI <10 at week 12 compared to the EEN (66) .…”

Microbial orchestra in juvenile idiopathic arthritis: Sounds of disarray?

“…More recently, so-called anti-inflammatory diets that attempt to recapitulate the nutritional contents of EEN while still providing essentially normal foods have been published. [137][138][139] The mechanisms by which EEN result in improvement are unclear; although the microbiota is altered, this is not necessarily responsible for the clinical improvement, as the alteration may actually make the microbiota even more dysbiotic as evidenced by lower alpha diversity and lower fecal abundance of F prausnitzii. 140 EEN is the only dietary approach for which there are published data in JIA.…”

Plant‐ and Fish‐Derived n‐3 PUFAs Suppress Citrobacter Rodentium–Induced Colonic Inflammation

“…The etiology of IBD is unclear, involving a complex interplay between mucosal immunity, environment, and the gut microbiota . Evidence‐based dietary interventions are used to induce clinical remission and alleviate mucosal inflammation in children with IBD and allow better symptom management, decrease relapse rates, and offer cost‐effective low risk disease management . A western diet high in meats, cheese, and n ‐6 polyunsaturated fatty acids (PUFAs), but low in plants and n ‐3 PUFAs, promotes mucosal inflammation and the growth of enterobacteria, including adherent‐invasive Escherichia coli implicated in IBD .…”