Background Crohn’s disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with an unknown etiology. Several studies have identified dysregulated metabolites in patients with CD. However, there is significant variability in the metabolites found to be dysregulated across these studies, making it unclear whether a comprehensive, disease-specific metabolic signature for CD exists.

Objective To analyze Crohn’s disease-specific metabolomic studies and available datasets to identify a comprehensive signature of dysregulated metabolites and metabolic pathways implicated in human CD.

Design A comprehensive systematic review was conducted using Medline and Embase databases to identify studies (from inception to May 2024) that employed analytical chemistry techniques to quantify metabolites in various biological samples from Crohn’s disease patients and non-IBD controls. Metabolites that were significantly altered in Crohn’s patients and reported in at least two studies were included for further analysis.

Results The systematic search identified 3,632 studies, with 88 selected for data extraction. Across these studies, 79 metabolites were consistently reported as significantly altered in Crohn’s disease (CD) patients in two or more studies. These metabolites form a distinct metabolic signature that differentiates CD patients from non-IBD controls, highlighting their relevance in the pathophysiology of the disease.

Conclusion This systematic review presents a comprehensive and well-defined signature of dysregulated metabolites across various biological samples and provides detailed insight into the perturbed metabolic pathways involved in CD.

The authors have declared no competing interest.

This work was supported by UC Davis School of Medicine TriP program (MD and APA). The funding agencies had no role in the study analysis or writing of the manuscript. Its contents are solely the responsibility of the authors.

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The study used only publicly available human data.

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Conflict of Interest Disclosures: SHA is founder and principal of XenoMed LLC, which has interest in microbial metabolism; however, XenoMed had no role in the analyses or writing of the manuscript.

All data produced in the present study are available upon reasonable request to the authors