Age-Related Microbial Differences in Newly Diagnosed Crohn's Disease Reveal the Distinct Enrichment of Oral-Associated Taxa in Pediatric Patients.

BACKGROUND/AIMS: Crohn's disease (CD) presents differently by age of onset, but the microbial distinctions between pediatric and adult CD are currently unclear.

METHODS

In this study, the gut microbiota of fecal samples collected from newly diagnosed patients with CD (n=88; pediatric 44, adult 44) and their age- and sex-matched healthy controls (HCs, n=112) was analyzed using 16S rRNA gene amplicon sequencing. Differential abundance analysis was performed using MaAsLin2 to identify age-specific microbial signatures, and enterotypes were classified using Dirichlet multinomial mixture modeling.

RESULTS

Both pediatric and adult patients with CD exhibited shared dysbiosis characterized by reduced alpha diversity (p<0.001), enrichment of CD-associated pathobionts, such as Enterobacteriaceae and Enterococcaceae, and depletion of short-chain fatty acid-producing taxa within Ruminococcaceae and Lachnospiraceae. Notably, enterotyping revealed that individuals with CD converged toward a shared, pathobiont-dominated enterotype regardless of age, overriding the age-dependent stratification observed in HCs. Despite this shared convergence, differences in age-stratified comparisons were observed. Adult CD patients exhibited enrichment of resident pathobionts such as Ruminococcus gnavus and Clostridium innocuum, whereas pediatric CD patients exhibited unique and pronounced enrichment of Pasteurellaceae, Neisseriaceae, and Gemellaceae (false discovery rate <0.1).

CONCLUSIONS

In newly diagnosed patients, CD is characterized by shared dysbiosis and convergence toward a disease-specific enterotype across age groups. However, this was accompanied by distinct microbial features, specifically, the enrichment of taxa previously reported as prevalent in the oral microbiome in children versus resident pathobionts in adults. These findings suggest that age at disease onset is associated with age-stratified differences in microbial profiles in CD.