Abstract

Background: Changes in gut microbiome community structure are associated with the development of Crohn's Disease (CD) and can be altered by environmental factors such as diet. Exclusive enteral nutrition (EEN) can induce disease remission in more than 80% of pediatric CD patients. However, the mechanism of EEN effectiveness remains unclear and evidence-based dietary recommendations for remission maintenance after EEN cessation do not exist. We aimed to assess the influence of dietary fibre intake on microbiome composition and sustained remission. Methods: We conducted a cross-sectional analysis of 11 pediatric CD patients aged 11–17 years old who are participants in an ongoing study of microbiome changes in response to EEN. Participants had returned to their regular ad libitum diet for at least 3 months following 12-week EEN therapy, and completed a 79-item validated food frequency questionnaire (FFQ) to assess their fibre intake. Clinical sustained remission (SR) was indicated by weighted Pediatric Crohn's Disease Activity Index (wPCDAI) <12.5 by 6 month follow-up, otherwise participants were classified as non-sustained remission (NSR). 16S rRNA from participant stool samples collected at 12-week intervals was analysed using QIIME to assess changes in gut microbial diversity at time of EEN and following return to regular diet. Results: The dietary data revealed general low fibre intake (only 1 of 11 respondents consumed recommended amount of daily dietary fibre), so participants were classified as “higher fibre” if they consumed at least half the daily fibre recommendation for their age and sex, and “lower fibre” if they did not. Microbial beta diversity was significantly lower in patients consuming lower fibre compared to those consuming higher fibre (p=0.04, ANOSIM). There were no significant differences in alpha or beta diversity between patients consuming <600g of oral solid food (n=3) at time of FFQ and those consuming >600g. Microbial alpha diversity (Chao-1) analysis of patients' stool samples, after return to regular diet, showed the lowest gut microbial richness in patients who achieved remission with EEN but experienced disease flare (NSR) flare by 6 months follow-up (n=3), compared to EEN primary non-responders (n=2) and those in SR (n=4). Conclusions: Lower fibre intake is associated with decreased gut microbial diversity in pediatric CD patients after completing induction treatment with EEN. Persistence of decreased gut microbiome diversity with return to regular diet after EEN may indicate increased risk of disease flare. Further longitudinal analysis of microbiome changes associated with return to an oral diet after EEN are required to inform dietary therapy recommendations for maintenance of remission in pediatric CD.

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