Towards an integrated understanding of the therapeutic utility of exclusive enteral nutrition in the treatment of Crohn's disease

Abstract

Crohn's disease (CD) is a chronic disease characterized by episodic and disabling inflammation of the gastrointestinal tract in genetically susceptible individuals. The incidence and prevalence of CD is rising rapidly across the world emphasising that disease risk is also influenced by environmental and lifestyle factors, as well as the microbial community resident in the gut. Childhood-onset CD is associated with an aggressive disease course that can adversely impact patient growth and development. There is no cure for CD however new onset and recurrent cases of paediatric CD are often responsive to exclusive enteral nutrition (EEN) treatment. EEN treatment involves the exclusive consumption of an elemental or polymeric formula for several weeks and it is well established as a primary intervention strategy. EEN treatments typically achieve remission rates of over 80% and importantly they are associated with a high rate of mucosal healing, far superior to steroids, which is prognostic of improved long-term health outcomes. Furthermore, they are safe, have few side effects, and improve nutritional status and linear growth. Surprisingly, despite the utility of EEN our understanding of the host-microbe-diet interactions that underpin clinical remission and mucosal healing are limited. Here, we review the current state of knowledge and propose that the induction of autophagy, in addition to modulation of the microbiota and coordinated effects on inflammation and epithelial cell biology, may be critical for the therapeutic effects associated with EEN. A better understanding of EEN treatment will provide new opportunities to restore gut homeostasis and prolong periods of remission, as well as provide new insights into the factors that trigger and perhaps prevent CD.

Effects of the Exclusive Enteral Nutrition on the Microbiota Profile of Patients with Crohn’s Disease: A Systematic Review

“…It is plausible, however, that this effect simply reflects a general depletion of all the species already present in the gut at the start of the intervention rather than being a specific effect induced by EEN. In a recent review on the therapeutic utility of EEN in CD, Cuiv and their co-authors suggest that the effect of EEN on intestinal bacteria is mainly based on the limitation of growth and metabolic activity rather than the selection of a specific microbiological pattern [ 56 ]. The same authors proposed that the bowel rest induced by EEN may induce mucosal healing by limiting the activity of potentially pathogenic microbes and by enhancing repairing mechanisms (autophagy) [ 56 ].…”

“…In a recent review on the therapeutic utility of EEN in CD, Cuiv and their co-authors suggest that the effect of EEN on intestinal bacteria is mainly based on the limitation of growth and metabolic activity rather than the selection of a specific microbiological pattern [ 56 ]. The same authors proposed that the bowel rest induced by EEN may induce mucosal healing by limiting the activity of potentially pathogenic microbes and by enhancing repairing mechanisms (autophagy) [ 56 ]. The reduction at the end of EEN of F. prausnitzii , a butyrate producing bacteria considered to be protective towards CD development [ 37 , 38 ], reported by some studies [ 25 , 29 , 30 ] is in agreement with this hypothesis.…”

Enteral Nutrition in the Management of Pediatric and Adult Crohn’s Disease

“…More research is needed to determine how EEN compares to infliximab. Therapeutically, significant benefits of EEN include the excellent side effect profile, positive effects on growth and high rate of mucosal healing [ 40 ]. These benefits are offset by factors such as cost, palatability, and compliance.…”

Enteral nutrition is associated with a decreased risk of surgical intervention in Crohn’s disease patients with spontaneous intra-abdominal abscess

“…EN serves as an adjunctive therapy and has been widely used in a variety of diseases including abdominal sepsis (16), pancreatitis (17,18) and inflammatory bowel diseases (IBD) (5,(19)(20)(21)(22). A large body of evidence (5,8,21,(23)(24)(25)(26)(27)(28)(29)(30) suggests a beneficial role of EN in the management of CD. It is well known that malnutrition is common in CD patients.…”