Metabolomic Profiling of Fecal Samples Reveals Distinct Signatures Associated with Disease Phenotypes and Locations...

Crohn's disease is a heterogeneous, transmural inflammatory condition that can involve any segment of the gastrointestinal tract. Distinct locations (ileal, colonic, ileocolonic) and phenotypes (inflammatory, stricturing, penetrating) display different clinical behaviors and complication risks in CD. Whether these location- and phenotype-specific patterns correspond to unique metabolomic profiles remains incompletely defined.

To identify metabolites associated with disease activity, location, and phenotype, ultrahigh performance liquid chromatography-tandem mass spectroscopy-based metabolomic analysis was performed on stool samples from patients with CD. Active CD was defined as patients with fecal calprotectin above 100 μg/g. Metabolite differences among groups were assessed using permutational multivariate analysis of variance. Candidate metabolites were identified and validated using multivariable linear models adjusting for demographic covariates, with false discovery rate correction.

A total of 302 stool samples from patients with CD were analyzed. Complicated CD phenotypes (B2 and B3) showed increased acylcarnitines and secondary bile acids compared with inflammatory (B1) phenotype. Location-specific analysis indicated increased cholate, and N-acyl ethanolamides in ileal and ileocolonic compared to colonic CD. When stratified by inflammation using fecal calprotectin, patients with active disease displayed upregulation of methylysine, ceramide, sphingomyelin, and polyamines.

This study reveals metabolomic differences across CD phenotypes and disease activity, providing potential noninvasive biomarkers to help risk-stratify patients for complications and guide tailored management. Further validation in larger cohorts is warranted.