Microbial and functional shifts between flare and remission in a single-center cohort of children with inflammatory bowel disease

Abstract

BACKGROUND

Gut microbial dysbiosis is central to the pathogenesis of inflammatory bowel disease (IBD). While gut microbiome differences between patients with and without IBD are well established, microbiome changes associated with disease activity and remission remain limited, particularly in paediatric populations.

AIM

To examine intra-individual taxonomic and functional gut microbiome changes during transition from active flare to remission under maintenance immunosuppression in a pilot single-center Singapore cohort of children with IBD.

METHODS

Paired stool samples and clinical data were collected from seven patients with paediatric IBD [5 Crohn’s disease (CD), 2 ulcerative colitis; ≤ 18 years] during active disease/flare (visit 1; Pediatric CD Activity Index/Pediatric Ulcerative Colitis Activity Index ≥ 10) and subsequent clinical remission (visit 2; Pediatric CD Activity Index/Pediatric Ulcerative Colitis Activity Index < 10). Samples underwent shotgun metagenomic sequencing for high-resolution taxonomic profiling and functional annotation of Kyoto Encyclopaedia of Genes and Genomes pathways.

RESULTS

Gut microbial diversity was reduced during flare compared to remission, with Actinobacteria abundance significantly higher in remission. Two distinct microbial clusters differentiated flare and remission states: The remission cluster was enriched with Bifidobacterium adolescentis, Bifidobacterium dentium, Lactobacillus gasseri, Faecalibacterium prausnitzii, while the flare state showed increased Klebsiella pneumoniae. Remission was further characterized by a downregulation of pathogenic microbes and an upregulation of beneficial microbes including a higher abundance of the butyrate producer Anaerostipes hadrus (P = 0.046). Microbial functional genes enriched in remission were predominantly associated with metabolic pathways including vitamin and cofactor biosynthesis, as well as carbohydrate, amino acid, and lipid metabolism.

CONCLUSION

The transition from flare to remission in Singaporean children with IBD is characterized by functional remodeling of the gut microbiome, which may contribute to recovery processes related to intestinal barrier integrity, cellular maintenance, and tissue repair. Targeted modulation of the gut microbiome may help sustain remission in paediatric IBD.

Keywords: Inflammatory bowel disease; Pediatrics; Metagenomic; Gut microbiome; Microbial shift; Functional shift

Core Tip: Using a longitudinal paired design, this paediatric inflammatory bowel disease metagenomic study shows that transition from active disease to remission is marked by a distinct gut microbiome with functional relevance. Remission was associated with enrichment of beneficial taxa (Anaerostipes hadrus, Bifidobacterium spp., Faecalibacterium prausnitzii, Lactobacillus gasseri) and metabolic pathways supporting short-chain fatty acid production, epithelial barrier repair, and immune modulation, whereas flare was dominated by Klebsiella pneumoniae. These findings highlight microbiome-derived functional pathways as promising targets for non-invasive biomarkers and microbiome-based therapeutic strategies to sustain remission in paediatric inflammatory bowel disease.