Treatment of active Crohn's disease with an ordinary food-based diet that replicates exclusive enteral nutrition

Svolos, Vaios and Hansen, Richard and Nichols, Ben and Quince, Chrisopher and Ijaz, Umer Z. and Papadopoulou, Rodanthi T. and Edwards, Christine A. and Watson, David and Alghamdi, Adel and Brejnrod, Asker and Ansalone, Cecilia and Duncan, Hazel and Gervais, Lisa and Tayler, Rachel and Salmond, Jonathan and Bolognini, Daniele and Klopfleisch, Robert and Gaya, Daniel R. and Milling, Simon and Russell, Richard K. and Gerasimidis, Konstantinos (2019) Treatment of active Crohn's disease with an ordinary food-based diet that replicates exclusive enteral nutrition. Gastroenterology, 156 (5). pp. 1354-1367. ISSN 0016-5085

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    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 received CD-TREAT with clinical activity and fecal calprotectin evaluated after 8-week treatment.  Results Among 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), 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 log10 16S rRNA gene copies/g), short-chain fatty acids, microbiome, and ileitis severity (mean histopathology score reductions 1.25 for EEN (P=.015) and 1.0 for CD-TREAT (P=.044) vs chow). Among the children receiving CD-TREAT, 4 (80%) had a clinical response and 3 (60%) entered remission, with significant concurrent reductions in fecal calprotectin (mean decrease 918±555 mg/kg, (P=.002)).  Conclusion CD-TREAT replicates EEN changes in the microbiome, reduces gut inflammation, is well-tolerated and is potentially effective in patients with active CD.