Ecological mechanisms drive stool microbiome and mycobiome community assembly in paediatric Crohn's disease

Résumé fourni par la source

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 inflammatory bowel disease cases and matched controls. CD bacterial and fungal 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 in the microbiome, 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 positively correlated with identified key CD bacterial taxa and a biochemical marker of inflammation. A reduction in disease activity, following CD treatment, was associated with a reduction in stochasticity and in some 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.

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