Nutritional therapy for patients with Crohn’s Disease moves into the frontline
Dror Shouval, P-ECCO Member
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In the last decade, numerous biologics and small molecules have been tested in clinical trials for patients with Crohn’s Disease (CD), and some have already been approved and used effectively in such patients. However, there is increasing interest in the use of dietary therapies for patients with CD from both providers and patients, who often wish to start an intervention that is not associated with immunosuppression. In addition, studies in both animal models and humans have put the spotlight on different dietary components that can either provoke or suppress intestinal inflammation. As an example, specific emulsifiers that are widely used in the food industry as preservatives increase the susceptibility of mice to develop colitis [1] and also alter the faecal microbiome and metabolome in humans characterised by pro-inflammatory perturbations [2].
In children with CD, a 6- to 8-week course of exclusive enteral nutrition (EEN) is used extensively for induction of remission and, according to the ECCO-ESPGHAN guidelines, EEN is considered first-line therapy in low-risk paediatric CD patients with a B1 inflammatory phenotype [3]. It is well established that there is no difference between use of a polymeric or an elemental formula, and the former is typically associated with better compliance. Such nutritional therapy is highly effective in inducing remission (up to 85%) in paediatric patients with CD but is difficult for patients and their families and is a short-term solution that does not address the need for subsequent maintenance therapy. This has led many groups to try to develop novel dietary interventions that are more palatable, while still being able to induce remission effectively.
The Crohn’s Disease Exclusion Diet (CDED) is based on a combination of partial enteral nutrition with a whole-food diet from which animal fat, red meat, wheat, dairy products, emulsifiers, maltodextrin and carrageenans are excluded. A two-step 12-week CDED intervention has been shown to be comparable to EEN in inducing remission in paediatric patients with mild-moderate CD (≥75%) [4, 5], but is significantly more tolerable [4]. Similar efficacy has also been shown in adult CD patients [6]. Mechanistically, the CDED is associated with marked changes in microbiome and metabolic profiles, including a reduction in specific kynurenine pathway compounds and an increase in serotonin [4, 7, 8]. Another food-based diet is the CD-TREAT, which has also been shown to be effective in inducing remission in patients with active CD, while replicating EEN-associated microbiome changes. Further nutritional interventions currently being tested in clinical trials include the Tasty and Healthy diet and the Crohn’s Disease Therapeutic Dietary Intervention (CD-TDI), among others.
One of the main limitations to date in the development of dietary therapies for CD has been the high likelihood of relapse once the intervention stops, if no maintenance drugs are commenced. An important finding reported by Yanai and colleagues is that the CDED can also be used in some CD patients to maintain clinical (and even endoscopic) remission, without the use of immunosuppressive drugs [6]. While this observation needs to be validated in a larger group of patients, it highlights the possibility of utilising dietary therapies for long periods of time, even without concomitant drugs, which could be a real breakthrough in the field. Understanding how specific dietary components affect the microbial and metabolic landscape in the gut, and consequently mucosal immune responses, should aid in this process, the aim being to achieve personalised dietary therapies according to phenotype, age, complications and baseline microbiome profile.
References
- Chassaing B, Koren O, Goodrich JK, et al. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome. Nature 2015;519:92–6.
- Chassaing B, Compher C, Bonhomme B, et al. Randomized controlled-feeding study of dietary emulsifier carboxymethylcellulose reveals detrimental impacts on the gut microbiota and metabolome. Gastroenterology 2022;162:743–56.
- van Rheenen PF, Aloi M, Assa A, et al. The medical management of paediatric Crohn's disease: An ECCO-ESPGHAN guideline update. J Crohns Colitis 2020;15:171–94.
- 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.
- Niseteo T, Sila S, Trivić I, Mišak Z, Kolaček S, Hojsak I. Modified Crohn's Disease Exclusion Diet is equally effective as exclusive enteral nutrition: Real-world data. Nutr Clin Pract 2022;37:435–41.
- Yanai H, Levine A, Hirsch A, et al. The Crohn's Disease Exclusion Diet for induction and maintenance of remission in adults with mild-to-moderate Crohn's disease (CDED-AD): an open-label, pilot, randomised trial. Lancet Gastroenterol Hepatol 2022;7:49–59.
- Verburgt CM, Dunn KA, Ghiboub M, et al. Successful dietary therapy in paediatric Crohn's disease is associated with shifts in bacterial dysbiosis and inflammatory metabotype towards healthy controls. J Crohns Colitis 2023;17:61–72.
- Ghiboub M, Sigall Boneh R, Sovran B, et al. Sustained diet-induced remission in pediatric Crohn's disease is associated with kynurenine and serotonin pathways. Inflamm Bowel Dis 2023;29:684–94.