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

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