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Background and aims Nutritional therapy with the Crohn's Disease Exclusion Diet + Partial Enteral Nutrition [CDED+PEN] or Exclusive Enteral Nutrition [EEN] induces remission and reduces inflammation in mild-to-moderate paediatric Crohn's disease [CD]. We aimed to assess if reaching remission with nutritional therapy is mediated by correcting compositional or functional dysbiosis. Methods We assessed metagenome sequences, short chain fatty acids [SCFA] and bile acids [BA] in 54 paediatric CD patients reaching remission after nutritional therapy [with CDED + PEN or EEN] [NCT01728870], compared to 26 paediatric healthy controls. Results Successful dietary therapy decreased the relative abundance of Proteobacteria and increased Firmicutes towards healthy controls. CD patients possessed a mixture of two metabotypes [M1 and M2], whereas all healthy controls had metabotype M1. M1 was characterised by high Bacteroidetes and Firmicutes, low Proteobacteria, and higher SCFA synthesis pathways, and M2 was associated with high Proteobacteria and genes involved in SCFA degradation. M1 contribution increased during diet: 48%, 63%, up to 74% [Weeks 0, 6, 12, respectively.]. By Week 12, genera from Proteobacteria reached relative abundance levels of healthy controls with the exception of E. coli. Despite an increase in SCFA synthesis pathways, remission was not associated with increased SCFAs. Primary BA decreased with EEN but not with CDED+PEN, and secondary BA did not change during diet. Conclusion Successful dietary therapy induced correction of both compositional and functional dysbiosis. However, 12 weeks of diet was not enough to achieve complete correction of dysbiosis. Our data suggests that composition and metabotype are important and change quickly during the early clinical response to dietary intervention. Correction of dysbiosis may therefore be an important future treatment goal for CD. [ABSTRACT FROM AUTHOR]

Introduction: Current therapies in pediatric Inflammatory Bowel Diseases (IBD) target the immune system and often fail to sustain long-term remission. There is a high need for development of alternative treatment strategies such as antibiotics in pediatric IBD. Areas covered: This study systematically assessed efficacy and safety of antibiotics in pediatric IBD. CENTRAL, EMBASE, and Medline were searched for Randomized Controlled Trials (RCTs). Quality assessment was conducted with the Cochrane risk-of-bias tool. Expert opinion: Two RCTs (n = 101, 4.4–18 years, 43% male) were included. Both studies had overall low risk of bias. In mild-to-moderate Crohn's disease, azithromycin+metronidazole (AZ+MET) (n = 35) compared to metronidazole (MET) alone (n = 38) did not induce a significantly different response (PCDAI drop ≥12.5 or remission) (p = 0.07). For induction of remission (PCDAI≤10), AZ+MET was more effective than MET (p = 0.025). In Acute Severe Colitis, mean 5-day-PUCAI was significantly lower in the antibiotic (vancomycin, amoxicillin, metronidazole, doxycycline)+intravenous-corticosteroids group (AB+IVCS) (n = 16) compared to IVCS alone (n=12) (p = 0.037), whereas remission (PUCAI<10) did not differ (p = 0.61). No significant drug-related adverse events were reported. Results of this systematic review of antibiotic use highlight the lack of evidence in pediatric IBD. More evidence is needed before widespread implementation in daily practice. [ABSTRACT FROM AUTHOR]