The microbiome and mycobiome ecology of paediatric Crohn's disease

Crohn's disease (CD) is a chronic inflammatory disorder with increasing incidence in children. Dysbiosis of the gut microbiome is characteristic of CD but the underlying pathogenic mechanisms are uncertain. There is a need to decipher how microbial communities are structured to better understand this complex disease. Ecological analytical approaches including community assembly processes based on the null model and dynamic core microbiome analyses were applied to the stool microbiome and mycobiome of an inception cohort of paediatric IBD cases and matched controls. CD fungal and bacterial signatures were less homogeneous than controls with CD diagnosis and severity of disease accounting for the most variation. Stochastic processes were identified as more common in structuring the CD microbiome than controls. Together with a reduction in alpha diversity, this indicates a less stable environment allowing opportunistic species to colonise; key CD associated taxa were Fusobacterium, Aggregatibacter and Clavispora-Candida. Integration of omics demonstrated volatile metabolites (including phenol and propan-1-ol) and functional genomic pathways (including for virulence and antimicrobial resistance) positively correlated with identified key CD bacterial taxa and a biochemical marker of inflammation (faecal calprotectin). A reduction in disease activity following CD treatment was associated with a reduction in stochasticity and CD-associated taxa alongside a shift in the core microbiome towards the control profile. Our study has identified mechanisms that underpin variability in CD microbiota during disease. Further longitudinal studies are required to investigate how microbial community structure changes with relapse, remission and the implications for novel therapies.