Crohn's disease gut microbiome by gastrointestinal transit time
Introduction: We investigated relationships between disease activity measures and the gut microbiome in children with Crohn's disease (CD), and how these were confounded by gastrointestinal transit time.  Methods: Microbiome was profiled (16S rRNA sequencing) in faeces from 196 children with CD. 60 participants also provided samples after 18 months. Mural inflammation (paediatric inflammatory Crohn's magnetic resonance enterography index, PICMI), the simple endoscopic score for CD and the weighted paediatric Crohn's disease activity index (wPCDAI) were assessed. Faecal calprotectin, plasma CRP and faecal water content (FWC), a proxy of gastrointestinal transit time, were measured too.   Results: Microbiome a diversity, clustering and differential taxa were related to disease status, but varied remarkably by disease activity measure used. The strongest relationships between microbiome and disease activity status were observed using wPCDAI; fewer or no relationships were seen using more objective measures like PICMI. Taxa predictive of disease activity status were dependent on the disease activity measure used with negligible overlap. Active disease was associated with more pathobionts (e.g Viellonella, Enterobacterales) and fewer fibre-fermenting organisms. The effect FWC had on microbiome superseded the effect of active disease for all disease activity measures, particularly with wPCDAI. Accounting for FWC, the differences in microbial signatures explained by disease activity status were attenuated or lost. Conclusions: In CD, microbiome signatures fluctuate depending on the measure used to assess disease severity; several of these signals might be secondary disease effects linked with changes in gut motility in active disease. PICMI appears to be less influenced when studying relationships between microbiome and mural inflammation in CD.