Gut microbial functional associations with subsequent irritable bowel syndrome in a prospective, paediatric case–control study

Background The infant gut microbiome undergoes rapid maturation that shapes lifelong gastrointestinal health. Although adults with irritable bowel syndrome (IBS) show characteristic microbial and metabolic alterations, it remains unclear whether these differences precede disease onset. Here, microbiome composition and function in infancy were prospectively associated with future IBS development. Methods Stool samples collected from the All Babies in Southeast Sweden (ABIS) cohort at a mean age of 12.4 (±1.5) months, were analysed using a nested case–control design. Cases included future IBS and/or pelvic and abdominal pain, with the average time between age at stool collection and diagnosis being 11.8 (±5.2) years and a mean age at diagnosis of 12.8 (±5.2) years. Microbial composition was profiled with 16S rRNA gene sequencing (n = 396). Data were processed with DADA2, taxonomically assigned using SILVA database, and predicted functionally with PICRUSt2. Descriptive statistics were analysed using χ 2 or Fisher's exact test, global differences with PERMANOVA, differential abundance with ANCOM-BC2, and pathway enrichment with GSEA. Findings Infants with future IBS risk demonstrated microbial divergence, marked by depletion of short-chain fatty acid producers and expansion of facultative and mucosa-disruptive taxa. Inferred functional profiles exhibited reduced fermentative capacity, greater respiratory potential, accelerated degradation of neuroactive aromatic amines, and case-enrichment of cytochrome bc1 complex respiratory unit. Interpretation Gut microbiome dysbiosis in infants with IBS risk is present many years prior to diagnosis and includes early disruptions in fermentation, redox balance, and amine metabolism that potentially compromise epithelial resilience and promote visceral hypersensitivity. Early detection of microbiome dysbiosis suggests probiotic-based interventions. Funding Barndiabetesfonden; Swedish Council for Working Life and Social Research; Swedish Research Council; Östgöta Brandstodsbolag; Medical Research Council of Southeast Sweden; JDRF-Wallenberg Foundation; Linköping University; Horizon Europe INITIALISE grant.