Y-ECCO Literature Review: Paul Harrow
Crohn’s Disease exclusion diet plus partial enteral nutrition induces sustained remission in a randomized controlled trial
Levine A, Wine E, Assa A, Boneh RS, Shaoul R, Kori M, Cohen S, Peleg S, Shamaly H, On A, Millman P, Abramas L, Ziv-Baran T, Grant S, Abitbol G, Dunn KA, Bielawski JP, Van Limbergen J
© Paul Harrow
Exclusive enteral nutrition (EEN) is a safe and effective induction treatment for Crohn’s Disease (CD). It is recommended as first-line induction therapy in children and adolescents . However, enteral nutrition is less well tolerated than other options like corticosteroids. A recent meta-analysis found three times as many patients withdrew from enteral nutrition therapy compared to corticosteroids even in the supported setting of clinical trials . There is a clear need for a more acceptable dietary intervention. However, our understanding of the role of diet in CD is incomplete and to date specific diets have not been proven to induce remission.
This study proposes the CD Exclusion Diet (CDED), described as a whole-food diet, and compares the tolerability and efficacy of this diet coupled with partial enteral nutrition (PEN) to EEN in children recently diagnosed with mild-moderate CD.
Patients were randomised 1:1 to receive either the CDED with 50% PEN (using Modulen®) or EEN for the first 6 weeks followed by CDED with 25% PEN or 25% PEN with standard reintroduction of food.
Mandatory foods in the CDED were chicken, eggs, peeled potatoes, apples and bananas. In the first 6 weeks only 12 other foods were permitted, plus a limited list of seasonings. A wide variety of processed foods, all dairy products, wheat products, nuts and snack foods were proscribed, including most fruits and vegetables . In weeks 6–12 the variety of permitted food was broadened. However, all dairy, wheat and processed foods were still disallowed .
The primary outcome of the study was patient tolerance to the diet at week 6, defined by withdrawal from the study. A non-inferiority study was deemed impossible due to the predicted requirement for very large numbers of patients. Nonetheless, clinical end-points including the Paediatric Crohn's Disease Activity Index (PCDAI) and the inflammatory markers C-reactive protein (CRP) and calprotectin were reported at weeks 6 and 12.
Seventy-eight patients were randomised to each dietary strategy. The CDED + PEN diet was indeed better tolerated, with only 2.5% (1/40) failing to complete 6 weeks compared to 26.3% (28/38) for EEN. There was no significant difference in the rate of clinical response, defined as PCDAI decrease of ≥12.5 (85% in both groups), remission (PCDAI ≤10), CRP or calprotectin at 6 weeks . However, at 12 weeks important differences were observed between the groups. The proportion of patients in clinical remission taking the CDED + 25% PEN diet remained stable at 75.6%, while the proportion of patients in remission in the second group, who were also on 25% PEN but had restarted a standard diet, fell significantly to 45.1% (p=0.01). A striking pattern was seen with CRP and calprotectin, which continued to improve in the CDED group but rebounded upwards in patients taking a standard diet by week 12.
The authors also highlight a potential mechanism for these observations. Similar changes in microbial composition (using 16S sequencing) were observed at 6 weeks in both groups, with increased Clostridia and decreased Actinobacteria and Proteobacteria taxa. In the CDED group most of these changes were maintained while in the EEN group there was a striking reversal of the changes observed following the introduction of a standard diet.
This is the first randomised head-to-head trial comparing an ordinary food-based diet with the current standard of care EEN in paediatric CD. It shows that selection of specific foods can mimic the effect of EEN to induce remission but also, importantly, that patients tolerate this diet significantly better than an exclusive liquid regime.
Some important questions remain unanswered. The dietary restrictions particularly in the first 6-week period were wide ranging and it is not clear whether it is necessary to exclude all of these foods to achieve the same effect. This may also vary between individuals.
It is also unclear whether the addition of PEN is necessary. Another paper in the previous issue of this journal proposed an alternative diet, CD-TREAT, which was very similar to the CDED diet but did not include PEN. These authors suggested that a specific food diet alone recreates many of the bacterial taxa and metabolite changes observed with EEN .
Lastly, this study only reports the outcomes at 12 weeks. It will be interesting to see how many patients relapse after a return to a wider diet or are able to continue the CDED in the longer term.
It seems likely that this study will be a popular topic of conversation with patients this year and may herald a paradigm shift from EEN to whole food-based dietary therapies for CD.
- Ruemmele FM, Veres G, Kolho KL, et al. Consensus guidelines of ECCO / ESPGHAN on the medical management of pediatric Crohn’s disease. J Crohns Colitis. 2014;8:1179–207.
- Narula N, Dhillon A, Zhang D, Sherlock ME, Tondeur M, Zachos M. Enteral nutritional therapy for induction of remission in Crohn’s disease (review). Cochrane Database Syst Rev. 2018 Apr 1;4:CD000542. doi: 10.1002/14651858.CD000542.pub3.
- Nestle. The Crohn’s Disease Exclusion Diet - Phase I Week 0 to 6. (2019).
- Nestle. The Crohn’s Disease Exclusion Diet - Phase II Week 7 to 12. (2019).
- Levine A, Wine E, Assa A, et al. Crohn’s Disease Exclusion Diet plus partial enteral nutrition induces sustained remission in a randomized controlled trial. Gastroenterology 2019;157:440–50.e8.
- Svolos V, Hansen R, Nichols B, et al. Food-based diet that replicates exclusive enteral nutrition. Gastroenterology. 2019;156:1354–67.
Paul Harrow is a gastroenterology trainee at the Royal London Hospital and QMUL. He is exploring the role of the aryl hydrocarbon receptor, an environmental sensor, in the intestine and has an interest in eHealth in IBD.