Dietary triggers of gut inflammation following exclusive enteral nutrition in children with Crohn's disease: a pilot study

Konstantinos Gkikas, Michael Logan, Ben Nichols, Umer Z Ijaz, Clare M Clark, Vaios Svolos, Lisa Gervais, Hazel Duncan, Vikki Garrick, Lee Curtis, Elaine Buchanan, Tracey Cardigan, Lawrence Armstrong, Caroline Delahunty, Diana M Flynn, Andrew R Barclay, Rachel Tayler, Simon Milling, Richard Hansen, Richard K Russell, Konstantinos Gerasimidis, Konstantinos Gkikas, Michael Logan, Ben Nichols, Umer Z Ijaz, Clare M Clark, Vaios Svolos, Lisa Gervais, Hazel Duncan, Vikki Garrick, Lee Curtis, Elaine Buchanan, Tracey Cardigan, Lawrence Armstrong, Caroline Delahunty, Diana M Flynn, Andrew R Barclay, Rachel Tayler, Simon Milling, Richard Hansen, Richard K Russell, Konstantinos Gerasimidis

Abstract

Background: The anti-inflammatory effect of exclusive enteral nutrition on the gut of children with Crohn's disease is rapidly lost after food reintroduction. This study assessed disease dietary triggers following successful treatment with exclusive enteral nutrition.

Methods: Nutrient intake, dietary patterns and dietary biomarkers in faeces (gluten immunogenic peptides, undigestible starch, short chain fatty acids) were assessed in 14 children with Crohn's disease during early food reintroduction, following exclusive enteral nutrition. Groups above (Group A) and below (Group B) the median levels of faecal calprotectin after food reintroduction were assigned for comparative analysis.

Results: Intakes of fibre, gluten-containing cereals and red and processed meat were significantly higher in Group A than Group B; (median [Q1, Q3], g/day; Fibre: 12.1 [11.2, 19.9] vs. 9.9 [7.6, 12.1], p = 0.03; Red and processed meat: 151 [66.7, 190] vs. 63.3 [21.7, 67], p = 0.02; gluten-containing cereals: 289 [207, 402] vs. 203 [61, 232], p = 0.035). A diet consisting of cereals and meat products was predictive (92% accuracy) of higher faecal calprotectin levels after food reintroduction. In faeces, butyrate levels, expressed as absolute concentration and relative abundance, were higher in Group A than Group B by 28.4 µmol/g (p = 0.015) and 6.4% (p = 0.008), respectively. Levels of gluten immunogenic peptide and starch in faeces did not differ between the two groups.

Conclusions: This pilot study identified potential dietary triggers of gut inflammation in children with Crohn's disease after food reintroduction following treatment with exclusive enteral nutrition.

Trial registration: Clinical trials.gov registration number: NCT02341248; Clinical trials.gov URL: https://ichgcp.net/clinical-trials-registry/NCT02341248 (retrospectively registered).

Keywords: Crohn’s disease; Dietary triggers; Faecal calprotectin; Fibre; Food reintroduction; Gluten; Meat; Short chain fatty acids.

Conflict of interest statement

RH has received speakers/consultancy fees or conference support from Nutricia, and 4D Pharma. RKR has received speaker's fees, travel support and/ or participated in medical board meetings with Nestle, MSD Immunology, AbbVie, Dr Falk, Takeda, Napp, Mead Johnson, Nutricia & 4D Pharma. RH & RKR are supported by an NHS Research Scotland Senior Career Researcher Fellowship. K Gerasimidis has received research grants, speakers’ fees and had conference attendance paid by Nutricia/Nestle, Nutricia-Danone, Baxter, Abbott, and Dr Falk. The rest of the authors (K Gkikas, ML, BN, UZI, CMC, VS, LG, HD, VG, LC, EB, TC, LA, CD, DMF, ARB, RT and SM) have no competing interests to report.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Comparison of food group intake between the two groups in children with Crohn's Disease during food reintroduction. Group A: patients with faecal calprotectin levels above the median levels at food reintroduction, Group B: patients with faecal calprotectin values below the median levels at food reintroduction * Intake of non-alcoholic beverages has been divided by 10 for both groups for better visualisation. Red diamond indicates significant differences between Group A and B (p = 0.03)
Fig. 2
Fig. 2
Correlations between nutrient and food intake with faecal calprotectin levels in children with Crohn's Disease after food reintroduction
Fig. 3
Fig. 3
Results from subset regression analysis showing food-group models predicting classification of patients in the two FC groups. Food groups coloured with red indicate positive association (i.e., harmful) and with blue negative (i.e., beneficial) association with assignment of patients in the group with higher FC levels during food reintroduction (Group A) (higher FC levels during food reintroduction). OOB error: Out of bag error rate, showing percentage of misclassification of patients to their respective FC groups (Group A/B) for each different food-group model identified from random forest analysis. Fish and fish-related products were removed from analysis, as they were consumed by one patient

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