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Oral presentations: Scientific Session 6: Cartels in IBD (Part 2) (2020)

OP22 Crohn’s disease exclusion diet reduces bacterial dysbiosis towards healthy controls in paediatric Crohn’s disease

J. Van Limbergen1, K. Dunn2, E. Wine3, R. Sigall Boneh4, J. Bielawski2, A. Levine4

1Division of Pediatric Gastroenterology and Nutrition, Amsterdam UMC - Location AMC, Amsterdam, The Netherlands, 2Department of Biology, Dalhousie University, Halifax, Canada, 3Department of Paediatric Gastroenterology and Nutrition, University of Alberta, Edmonton, Canada, 4Wolfson Medical Centre, Paediatric Gastroenterology & Nutrition, Holon, Israel

Background

Dietary therapy with the Crohn’s disease Exclusion Diet (CDED) or Exclusive Enteral Nutrition (EEN) induces remission, reduces inflammation and is associated with compositional changes in the microbiome. We performed metagenome analysis to elucidate whether diet induces remission via correction of dysbiosis and/or community structure.

Methods

Whole metagenome and 16S rDNA sequences were obtained in 178 samples from 70 participants at 3 time points (baseline, week 6, week 12) from the two study groups (CDED+PEN/EEN). For metagenome analysis, we divided the groups further into samples of patients achieving ITT-remission at week 6 (CDED+PEN: 31/38 and EEN: 23/32) and those who did not.

Results

Dietary therapy decreased the relative abundance of genera from Proteobacteria towards healthy controls. CDED+PEN remission is associated with a significant increase (p < .05) in Clostridiales, and a significant decrease (p < .05) in Proteobacteria (particularly Γproteobacteria). Microbiome comparison of all baseline CD samples with healthy controls showed significant (p < .05) increases in Proteobacteria in an active CD at baseline. Healthy controls had increased Firmicutes species notably Roseburia, Oscillibacter and Anaerostipes, as well as increased Bacteroides and Ascomycota (driven by Saccharomyces). Proteobacteria decreased when diet-induced remission was achieved (with either CDED+PEN or EEN) at week 6: relative abundance of Proteobacteria (including Α- and Γproteobacteria (e.g. Escherichia, Klebsiella and Citrobacter) were significantly lower compared with baseline but were still more abundant in CD patients, whereas Bacilli and Firmicutes remained more predominant in healthy samples. Continued dietary treatment with CDED+PEN between week 6 and week 12 was associated with a further decrease in Proteobacteria: although improving with dietary treatment, only Escherichia remained more abundant in CD. Faecalibacterium became more abundant in CD by week 12, as did Blautia and Sutterella. Anaerostipes, Ruminococcus, Bacilli, Porphyromonadaceae, Bifidobacteriales, Ascomycota and Caudovirales were more abundant in healthy samples compared with week 12 of CDED+PEN. Bayesian analysis of the 16S rDNA data training on patients in remission at week 6 compared with baseline (week 0) samples identified seven assemblages. Predominate taxa identified in these assemblages (Posterior Probability >.01) are shown as a connected network, with taxa (nodes) found in the same assemblage connected to each other by edges (Figures).

Conclusion

Dietary therapy corrected dysbiosis towards healthy controls. Sustained dietary therapy beyond 6 weeks with CDED+PEN avoids the ‘rebound’ in disease-associated species, notably Proteobacteria, when the oral diet is reintroduced.