Review article: Mechanisms underlying the effectiveness of exclusive enteral nutrition in Crohn's disease

Summary Background Exclusive enteral nutrition (EEN) induces remission and mucosal healing in patients with Crohn's disease, but the mechanism of action remains unknown. Aim To outline current understanding of the mechanisms of action of EEN. Methods From a comprehensive literature search, published data were critically examined in a narrative review. Results Multiple potential mechanisms of action have been identified. EEN optimises nutritional status. Differences in gut microbiota in terms of overall diversity and taxonomic community structure are observed between responders and non‐responders to EEN. Therapy with EEN alters microbial metabolites (including faecal short‐chain fatty acids, amino acids, branched‐chain amino acids and sulphide) and faecal pH. Epithelial effects and restoration of barrier function, as well as changes in mucosal cytokine profiles and T‐cell subsets are observed in responders to EEN. The impact of inclusion or exclusion of specific dietary components may be of importance, but putative detrimental components are found in many formulas. A major challenge in interpreting these findings is that they often contradict or change in opposite directions to what is considered ‘beneficial’. It is difficult to differentiate between the observations following EEN being driven by EEN per se and those associated with resolving inflammation. Conclusions The mechanisms of action of EEN are likely to involve a complex interplay between host mucosal immune response and luminal environment, but the identity of key factors remains poorly understood. A better definition of pathogenic factors may aid in developing more targeted dietary treatment and provide insights into the pathogenesis of Crohn's disease.