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TOPLINE:

Metabolomic profiling of fecal samples from patients with Crohn’s disease (CD) revealed that complicated disease phenotypes (stricturing and penetrating) were metabolically distinct from inflammatory phenotypes, exhibiting elevated levels of acylcarnitines and secondary bile acids. Furthermore, active disease showed a marked overexpression of ceramides, sphingomyelins, and polyamines, and ileal and ileocolonic disease showed increased levels of primary bile acids compared with colonic disease.

METHODOLOGY:

• Currently available noninvasive biomarkers cannot reliably distinguish inflammatory from complicated CD, creating an urgent need for better monitoring and predictive tools. Fecal metabolomic profiling can offer a comprehensive way to discover CD-specific biomarkers and therapeutic targets.
• Researchers used an untargeted mass spectrometry-based approach to identify distinct metabolite signatures associated with disease location, activity, and phenotype.
• They analyzed stool samples from 302 well-characterized patients with CD (median age, 41.5 years; 62.6% women) enrolled in a US-based longitudinal cohort; samples were collected at enrollment prior to endoscopy and linked to standardized patient‑reported outcomes and biospecimens.
• Metabolites were evaluated across disease activity (active vs inactive, with active disease defined as fecal calprotectin levels > 100 μg/g), location (colonic, ileal, or ileocolonic), and phenotype (inflammatory, stricturing, or penetrating).

TAKEAWAY:

• Overall, 43.4% of patients had inflammatory CD, 24.5% had stricturing disease, and 9.9% had predominant penetrating phenotypes; 43.4% had ileocolonic disease, 22.8% had ileal disease, and 16.2% had colonic disease.
• Patients with active CD showed a marked elevation of eight metabolites, notably lipids (ceramide and sphingomyelin) and polyamine (diacetylspermine), and had reduced pelargonate compared with those with inactive CD.
• Stricturing and penetrating phenotypes had higher levels of certain bile acids (cholate and 7-ketodeoxycholate), carnitines (palmitoylcarnitine and oleoylcarnitine), putrescine, and tryptamine than inflammatory CD phenotypes; however, the inflammatory phenotype had higher levels of 3-methylglutarate/2-methylglutarate, monosulfates, and urobilin.
• Location-specific analysis revealed elevated levels of several bile acids (cholate, 7-ketodeoxycholate, 7-ketolithocholate, and isoursodeoxycholate) and N-acyl ethanolamides in ileocolonic vs colonic CD, whereas levels of carbamoylsarcosine and urobilin were reduced in ileal and ileocolonic vs colonic CD.

IN PRACTICE:

“Overall, this study highlights the metabolic heterogeneity associated with CD phenotypes and anatomical locations. The distinct metabolite signatures identified — including acylcarnitines, bile acids, and polyamines — represent promising biomarkers that could improve disease stratification and enable earlier therapeutic interventions,” the authors of the study wrote.

SOURCE:

This study was led by Tingyi Tan, Washington University School of Medicine, St. Louis. It was published online in Digestive Diseases and Sciences.

LIMITATIONS:

Dietary habits, which were not reported in the study, could have influenced metabolite levels. The study lacked a comparison with healthy control individuals, which limited the ability to contextualize the findings.

DISCLOSURES:

This study was supported by a grant from the Crohn’s & Colitis Foundation and other sources. Two authors disclosed receiving research funding and/or having consulting relationships with pharma companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.