Microbial predictors of sustained clinical remission following the crohn’s disease exclusion diet in adults and microbiome shifts toward healthy paediatric controls

Abstract Background The Crohn’s Disease (CD) Exclusion Diet (CDED) is an emerging dietary therapy for inducing remission in CD. However, data on its effects on gut microbiome in adults remain limited. This study investigated microbial responses to CDED in adults with mild-to-moderate CD and compared them with paediatric patients and healthy paediatric controls. Methods Microbiome data were analysed from a randomized controlled trial (RCT) in adults (baseline, weeks 6, 12, 24) and a paediatric RCT (baseline, weeks 6, 12). Baseline microbial composition, diversity, and functional potential were compared between patients who achieved sustained clinical remission (SCR) at both weeks 12 and 24 and those who did-not. Functional profiling was performed using gene ortholog annotations, linear discriminant analysis, and metabolite inference. Results Baseline microbial and functional profiles differed between patients with and without SCR. SCR was associated with lower alpha diversity, higher relative abundances of Alistipes and Faecalibacterium, and increased flagellin gene expression. SCR was associated with enrichment of genes for redox balance, fatty acid metabolism, and DNA repair, while non-SCR showed elevated NAD biosynthesis, bacterial adhesion, and pro-inflammatory pathways. Haemophilus and Prevotella were negatively linked to SCR. Compositional and functional microbiome analyses revealed a microbiome shift during CDED-induced remission towards a profile more similar to healthy paediatric controls. Conclusions Before and during CDED, distinct baseline microbial and functional profiles were associated with SCR. These highlight the potential of the gut microbiome as a biomarker for identifying patients most likely to benefit from sustained effects of dietary therapy, supporting a more personalized approach to CD management.