Vaios Svolos, Richard Hansen, Ben Nichols, Christopher Quince, Umer Z Ijaz, Rodanthi T Papadopoulou, Christine A Edwards, David Watson, Adel Alghamdi, Asker Brejnrod, Cecilia Ansalone, Hazel Duncan, Lisa Gervais, Rachel Tayler, Jonathan Salmond, Daniele Bolognini, Robert Klopfleisch, Daniel R Gaya, Simon Milling, Richard K Russell, Konstantinos Gerasimidis
Journal: Gastroenterology 2019;156(5):1354-1367.e6
PMID: 30550821
Crohn’s disease (CD) is associated with high morbidity and increased health expenditure. The current paradigm of CD pathogenesis suggests an interaction between environmental factors and the gut microbiome. The main aim of this study was to develop a food diet based on the composition of exclusive enteral nutrition (EEN) and examine the effects on the gut microbiome. This study is a randomised controlled trial (RCT) which recruited healthy adults who were randomly allocated to one of the 2 groups: EEN group or CD-treatment group. The RCT was followed by experiments in animal models to explore the anti-inflammatory effect of CD-treatment and its effect on the gut microbiome in a disease state. Results indicate that when compared to EEN, the CD-treatment induced similar broad-spectrum alterations in the gut microbiome and provided similar efficacy in treating gut inflammation and improving clinical activity in healthy participants. Furthermore, several effects observed in the healthy participants were replicated in the animal experiments which featured microbial dysbiosis (imbalance) which is similar to human CD. Authors conclude that CD-treatment has the potential to be used interchangeably with EEN, especially in adults whom EEN uptake is low, and raises the prospect of long-term dietary maintenance therapy.
BACKGROUND & AIMS
Exclusive enteral nutrition (EEN) is the only established dietary treatment for Crohn's disease (CD), but its acceptability is limited. There is a need for novel dietary treatments for CD.
METHODS
We evaluated the effects of an individualized food-based diet (CD-TREAT), with similar composition to EEN, on the gut microbiome, inflammation, and clinical response in a rat model, healthy adults, and children with relapsing CD. Twenty-five healthy adults randomly received EEN or CD-TREAT for 7 days, followed by a 14-day washout period, followed by the alternate diet. Fecal microbiome and metabolome were assessed before and after each diet. HLA-B7 and HLA-B27 transgenic rats with gut inflammation received EEN, CD-TREAT, or standard chow for 4 weeks. Fecal, luminal, and tissue microbiome, fecal metabolites, and gut inflammation were assessed. Five children with active CD activity received CD-TREAT and their clinical activity and calprotectin were evaluated after 8 weeks of treatment.
RESULTS
For healthy adults, CD-TREAT was easier to comply with and more acceptable than EEN. CD-TREAT induced similar effects to EEN (EEN vs CD-TREAT) on fecal microbiome composition, metabolome, mean total sulfide (increase 133.0 ± 80.5 vs 54.3 ± 47.0 nmol/g), pH (increase 1.3 ± 0.5 vs 0.9 ± 0.6), and the short-chain fatty acids (μmol/g) acetate (decrease 27.4 ± 22.6 vs 21.6 ± 20.4), propionate (decrease 5.7 ± 7.8 vs 5.2 ± 7.9), and butyrate (decrease 7.0 ± 7.4 vs 10.2 ± 8.5). In the rat model, CD-TREAT and EEN produced similar changes in bacterial load (decrease 0.3 ± 0.3 log 16S rRNA gene copies per gram), short-chain fatty acids, microbiome, and ileitis severity (mean histopathology score decreases of 1.25 for EEN [P = .015] and 1.0 for CD-TREAT [P = .044] vs chow). In children receiving CD-TREAT, 4 (80%) had a clinical response and 3 (60%) entered remission, with significant concurrent decreases in fecal calprotectin (mean decrease 918 ± 555 mg/kg; P = .002).
CONCLUSION
CD-TREAT replicates EEN changes in the microbiome, decreases gut inflammation, is well tolerated, and is potentially effective in patients with active CD. ClinicalTrials.gov, numbers NCT02426567 and NCT03171246.
Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.
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