Exclusive enteral nutrition modulates the faecal metagenome in paediatric Crohn’s disease not by enriching the abundance of presumably ‘beneficial’ commensals but by suppressing ‘dysbiotic’ bacteria. Exclusive enteral nutrition in Crohn's disease

Background: Exploring the associations between the gut microbiota and colonic inflammation and assessing sequential changes during treatment may offer clues about their role in Crohn’s disease (CD). We characterised the fecal microbiome in CD children, explored correlations with calprotectin and studied changes during exclusive enteral nutrition (EEN). Methods: A maximum of five fecal samples (total n=117) were collected from 23 children with CD during EEN and 21 healthy controls. Sequencing of the 16S rRNA gene and shotgun metagenomics were performed to characterise the microbial community structure and genetic functional capacity. Results: Taxonomic profiles distinguished CD patients receiving EEN from healthy controls (p=0.006). Thirty six genera, 141 operational taxonomic units (OTUs) and 44 oligotypes were significantly different between the two groups. During EEN, microbial diversity was reduced and the community structure became even more dissimilar from that of healthy controls. Thirty four bacterial genera significantly decreased and one (Lactococcus) increased during EEN. Thirty five OTUs correlated with fecal calprotectin, 14 of which explained 78% of calprotectin variation. OTUs which correlated both positively and negatively with calprotectin, decreased during EEN. CD microbiota presented a broader genetic functional capacity than healthy controls. This functional diversity also decreased during EEN. Genes involved in membrane transport, sulfate reduction, biosynthesis of fatty acids, lipids and carbohydrates differed between the two groups. The relative abundance of pathways implicated in biotin (p=0.005) and thiamine (p=0.0166) biosynthesis were decreased whereas spermidine/putrescine (p=0.0307) biosynthesis and shikimate pathway (p=0.058) were increased during EEN. Conclusions: Exclusive enteral nutrition a highly efficacious treatment for CD probably acts by modulating the entire microbiota, reducing inflammation-associated bacteria rather than increasing abundance of presumably beneficial commensals.