Stool Metabolites May Help Predict Crohn’s Disease Complications: Study
USA: Researchers have discovered in a new study that stool metabolomic profiling in patients with Crohn’s disease identified distinct metabolic patterns linked to disease complications. Stricturing and penetrating forms showed higher levels of acylcarnitines and secondary bile acids, while active disease was associated with elevated ceramides, sphingomyelins, and polyamines. Ileal and ileocolonic disease also demonstrated increased primary bile acids compared with colonic disease, suggesting stool metabolites may help predict disease behavior and severity.
The findings, published in Digestive Diseases and Sciences, provide new insights into how metabolic signatures in stool may reflect the biological diversity of Crohn’s disease (CD). The research was led by Tingyi Tan from the Division of Gastroenterology at Washington University School of Medicine, St. Louis, along with colleagues, who aimed to explore whether disease phenotype, activity, and location are associated with distinct metabolomic profiles.
Crohn’s disease is a chronic inflammatory disorder that can affect different parts of the gastrointestinal tract and present with varying clinical patterns, including inflammatory, stricturing, and penetrating disease. These variations are associated with differing risks of complications and treatment responses. However, identifying reliable, noninvasive markers that reflect these differences remains a key clinical challenge.
To address this, the researchers conducted metabolomic analysis on 302 stool samples collected from patients with CD using ultrahigh performance liquid chromatography–tandem mass spectrometry. Disease activity was determined using fecal calprotectin levels, with values above 100 μg/g indicating active inflammation. Advanced statistical methods were applied to identify metabolites associated with disease characteristics while adjusting for demographic factors.
Key Findings:
- Distinct metabolomic differences were observed across Crohn’s disease phenotypes.
- Patients with complicated disease forms, including stricturing and penetrating Crohn’s disease, showed higher levels of acylcarnitines and secondary bile acids compared with those having inflammatory disease.
- Disease location influenced metabolomic patterns, with ileal and ileocolonic disease showing elevated levels of cholate and N-acyl ethanolamides compared with colonic disease.
- Active inflammatory disease was associated with increased levels of methylysine, ceramides, sphingomyelins, and polyamines.
These findings suggest that metabolic alterations in stool not only reflect disease presence but also correlate with its severity and biological behavior.
Despite promising results, the study had key limitations. Marker performance was assessed in the same cohort, likely inflating accuracy and requiring external validation. Dietary influences and healthy control comparisons were not included. Single stool samples also limited evaluation of longitudinal changes.
Overall, the study highlights the metabolic diversity underlying Crohn’s disease and identifies potential noninvasive biomarkers that could aid in risk stratification and personalized management. The researchers emphasize that further large-scale and longitudinal studies are required to confirm these findings and determine the clinical utility of these metabolite signatures in guiding treatment decisions.
Reference:
Tan, T., Vincent, M., Jain, U. et al. Metabolomic Profiling of Fecal Samples Reveals Distinct Signatures Associated with Disease Phenotypes and Locations in Crohn’s Disease. Dig Dis Sci (2026). https://doi.org/10.1007/s10620-026-09779-9
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