An ordinary diet based on commonly eaten solid foods can replicate the physiological effects of exclusive enteral nutrition (EEN), the established but challenging dietary treatment for Crohn’s disease (CD), according to Scottish researchers.
Their small proof-of-principle study found “robust” evidence that an individualized, ordinary food-based diet known as CD-TREAT and similar in composition to EEN, was easier to tolerate than EEN but had comparable effects on the gut microbiome, inflammation reduction, and clinical response in children with relapsing CD and healthy adults.
“If successful, CD-TREAT has the potential to be used interchangeably with EEN, particularly in adults where EEN uptake is low, and raises the prospect of long-term dietary maintenance therapy,” wrote Konstantinos Gerasimidis, PhD, of the University of Glasgow, and colleagues in Gastroenterology.
While successful in about 80% of patients, the gut-healing EEN regimen is very restrictive, and acceptability is low over the long term. “It is therefore of critical importance that we use our understanding of CD pathogenesis and the mechanism of EEN action to develop new effective dietary therapies that are more acceptable and tolerable,” the authors wrote, adding that this currently unmet need was prioritized as one of 10 top research issues in inflammatory bowel disease by healthcare providers and patient groups.
The study randomized 25 healthy adults to receive EEN or CD-TREAT for 7 days, followed first by a 14-day washout period and then by cross-over to the alternate diet. The adults had a mean age of 24.5 and a mean body mass index of 22.4, and 52% were female.
Nutrient intake during CD-TREAT was more similar to that of EEN than the participants’ habitual diet, with participants consuming more total and saturated fat and less fiber and carbohydrates compared with their usual regimen, the researchers explained. Protein intake was higher than the habitual diet during CD-TREAT. No significant changes in weight were seen, and fecal microbiome and metabolome were assessed before and after each diet.
In addition, five children with active disease also received CD-TREAT, with clinical activity and fecal calprotectin evaluated after 8 weeks of treatment.
A typical day’s menu in the CD-TREAT diet for a 15-year-old boy with CD included the following foods (all lactose- and gluten-free):
- Breakfast: full-fat milk, rice breakfast cereal, and apple juice
- Lunch: white bread, cheddar, and cream cheese; lettuce, peeled cucumber, and chicken with rice soup
- Dinner: grilled salmon, mashed potatoes, cheese sauce
- Snacks: pineapple juice, peeled apple, rice pudding
The healthy adult participants reported that CD-TREAT was easier to comply with and more satiating than EEN, producing less hunger and less desire to eat between meals. While gastrointestinal symptoms were uncommon on both diets, the ratings for abdominal pain and diarrhea were higher for EEN than for CD-TREAT (both P=0.005)
The microbiome composition, fecal pH, short-chain fatty acids, total sulfide, fecal bacterial load, and fecal metabolome significantly changed in the same direction for both regimens. The mean total sulfide increases on EEN and CD-TREAT were 133.0±80.5 vs 54.3±47.0 nmol/g, and the pH increase was 1.3±0.5 vs 0.9±0.6.
Decreases (μmol/g) were as follows: short-chain fatty acid acetate 27.4±22.6 vs 21.6±20.4, propionate 5.7±7.8 vs 5.2±7.9, and butyrate 7.0±7.4 vs 10.2±8.5.
Many parallel changes in specific metabolites and species were observed, Gerasimidis and co-authors noted.
Among the children receiving CD-TREAT, four (80%) had a clinical response and three (60%) entered remission, with significant concurrent reductions in fecal calprotectin (mean decrease 918±555 mg/kg, P=0.002).
In a different part of the study, HLA-B7 and HLA-B27 transgenic rats with gut inflammation received EEN, CD-TREAT, or standard feed for 4 weeks. Fecal, luminal, and tissue microbiome, fecal metabolites, and gut inflammation were evaluated, and CD-TREAT and EEN were found to produce similar changes in bacterial load, short-chain fatty acids, microbiome, and ileitis severity histopathology scores.
Like EEN and antibiotics, CD-TREAT may deplete nutrients such as fiber that promote bacterial growth or create a luminal microenvironment that suppresses the functionality of inflammatory microbes, blunting activation of the gut-associated immune response in CD patients, the researchers explained.
Asked for his perspective on the findings, Jason K. Hou, MD, of Baylor College of Medicine in Houston, called the study “fascinating as an early demonstration of concept showing mechanistically how components of the gut microbiome can be modified by mimicking the effects of EEN with whole foods.”
“This is important because while the best data comes from EEN studies, for many patients, EEN is not a practical option,” he said. Many individuals are not able to tolerate EEN and some may even require feeding tubes. “While the study is not large enough to show a real difference and justify patients going on it, it lays the groundwork for larger clinical trials,” Hou added.
Among the preliminary study’s other limitations, the researchers said, was its reliance solely on fecal samples for microbiome analysis in the healthy volunteers, which may not have reflected the mucosal microbiome. Moreover, some of the outcome measures for which equivalence between EEN and CD-TREAT was inferred may have needed a larger sample size. In addition, the dietary interventions lasted 7 days in human adults and 4 weeks in rats, which is considerably shorter than the 6 to 8 weeks of EEN that CD patients typically receive.
The research was supported by the Glasgow Children Hospital Charity, the Catherine McEwan Foundation, the University of Glasgow and Nestle Health Science, the Natural Environment Research Council, NHS Research Scotland, the Medical Research Council, and Cure Crohn’s Colitis; the proprietary prepared foods in the study were donated by Nestle Health Science.
Gerasimidis and several other authors disclosed financial relationships with pharmaceutical companies and other commercial organizations, including, variously, Nutricia, MSD Immunology, 4D Pharma, Janssen, AbbVie, Shire, Celltrion, NAPP, Nestle, and Mead Johnson Nutrition.