Fecal microbial and metabolic signatures in children with very early onset inflammatory bowel disease

Very early onset inflammatory bowel disease (VEO-IBD) is a clinically distinct form of IBD manifesting in children before the age of six years. Disease in these children is especially severe and often refractory to treatment. While previous studies have investigated changes in the fecal microbiome and metabolome in adult and pediatric IBD, insights in VEO-IBD remain limited. This multi-omics analysis reveals changes in the fecal microbiome and metabolome in children diagnosed with VEO-IBD compared with age- and sexmatched healthy controls. Untargeted metabolomics analysis identified a depletion of short-chain N-acyl lipids and an enrichment of dipeptides, tripeptides, and oxo bile acids in children with VEO-IBD. Differential abundance analysis of 16S rRNA sequencing data showed lower abundance of beneficial bacteria such as Bifidobacterium and Blautia, and higher abundance of Lachnospira, Veillonella, and Bacteroides in VEO-IBD. Multi-omics integration revealed associations between the altered gut microbiome composition and metabolic dysregulation, specifically for the N-acyl lipids. This study offers unique insight into fecal microbial and metabolic signatures in VEO-IBD, paving the way for a better understanding of disease patterns and thereby more effective treatment strategies.