An individualized, food-based diet with similar composition of nutrients to exclusive enteral nutrition (EEN), causes similar changes in the microbiomes of patients with Crohn’s disease (CD), reduces gut inflammation, and is preferred by patients, researchers report in the April issue of Gastroenterology.
Non-medical treatments are needed for patients with CD. Diet can contribute to development of CD—the increase in disease incidence has paralleled changes in eating habits and food industrialization. Certain nutrients and food additives have been associated with CD risk. Researchers have therefore recommmended inclusion or exclusion of specific food components in CD management.
EEN is the only established dietary treatment for pediatric CD. EEN induces clinical remission in approximately 80% of patients and promotes healing of the intestinal mucosa. The therapeutic mechanisms of EEN are not fully understood, but it alters the intestinal microbiome and its effects are reversed when patients resumed their habitual diets.
Although EEN is an effective treatment for CD, it is a restrictive diet with limited acceptability, particularly for adults, that must be continued to maintain remission. If we could determine the features of EEN that promote restoration of a healthy microbiota and mucusal healing, we might be able to develop dietary therapies that are more acceptable and tolerable. Health professionals and patient groups have asked this to be a priority for CD research.
Vaios Svolos et al developed an ordinary food diet based on the composition of EEN, which they called CD-TREAT, and studied its effects on the intestinal microbiome in a crossover study of healthy subjects. They also studied its anti-inflammatory effects in rats and tested the ability of CD-TREAT to induce clinical remission and reduce intestinal inflammation in a pilot trial of children with active CD.
The diet was first tested in 25 healthy adults who were randomly assigned to groups given EEN (Modulen IBD) and the CD-TREAT for 7 days, with a 14-day washout period in between to restore the intestinal microbiome to its baseline state. During CD-TREAT, participants were provided with a food list from which to choose their preferred items. An individualized dietary plan was developed by the research dietitians providing their daily energy requirements. Fresh fecal samples were collected before and after each experimental diet, and fecal microbiomes and metabolites were analyzed.
The healthy adults found CD-TREAT easier to comply with and more acceptable than EEN. CD-TREAT induced similar effects to EEN on fecal microbiome composition, metabolome, mean total sulfide (increase 133.0 ± 80.5 vs 54.3 ± 47.0 nmol/g for EEN), pH (increase 1.3 ± 0.5 vs 0.9 ± 0.6), and levels of 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).
The relative abundance of 58 (49.3%) and 38 (32.3%) genera changed significantly after EEN and CD-TREAT, respectively. Twenty-eight of these genera changed in the same direction for the 2 dietary interventions. Fecal metabolomes also significantly changed toward the same direction after EEN and CD-TREAT.
In animal studies, HLA-B7 and HLA-B27 transgenic rats with gut inflammation were given EEN, CD-TREAT, or standard chow for 4 weeks. CD-TREAT and EEN produced similar changes in bacterial load (decrease 0.3 ± 0.3 log10 16S rRNA gene copies per gram), short-chain fatty acids, fecal microbiomes, and ileitis severity (mean histopathology score decreases of 1.25 for EEN and 1.0 for CD-TREAT vs chow).
In an open-label trial, 4 children with mild to moderate active luminal CD (wPCDAI score 22.5–42.5) who had been treated previously with EEN were given CD-TREAT exclusively for 8 weeks. Compliance to CD-TREAT was high. At the end of 8 weeks of treatment, 80% had a clinical responses and 60% entered clinical remission. Pediatric CD activity scores decreased from a baseline mean of 32.5 ±7.5 to 11.3±SD 9.2 and 7.5±7.4 at 4 and 8 weeks (see figure). There were significant concurrent decreases in fecal calprotectin (mean decrease 918 ± 555 mg/kg).
Svolos conclude that CD-TREAT replicates EEN changes in the microbiome, decreases gut inflammation, is well tolerated, and is potentially effective in patients with active CD. CD-TREAT has the potential to be used interchangeably with EEN, particularly in adults in whom EEN uptake is low, and might be used as long-term dietary maintenance therapy.