Background: Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with an elusive etiology. There are multiple studies which reported dysregulated metabolites in IBD patients. However, there lies a great variability in the patient population, disease location, disease state, biological samples, and metabolite detection techniques across the studies. All these variables add to the great heterogeneity in the detected metabolites, making it difficult to achieve a disease specific comprehensive signature of the metabolites. Objective: We aimed to analyze CD specific metabolomic studies and available datasets to provide a most accurate and comprehensive signature of dysregulated metabolites and metabolic pathways implicated in human CD. Design: A comprehensive, systematic review search was carried out using Medline and Embase databases to search the studies (inception to May 2024) which used analytical chemistry techniques to quantify the metabolites in different biological samples of Crohn's patients and non-IBD controls. Metabolites significantly altered in Crohn's patients and reported in at least 2 studies were included and considered for further analysis. Results: The systematic search yielded 3,632 studies, with 88 selected for data extraction. Across these studies, 79 metabolites were found to be significantly altered in CD patients in two or more studies. These metabolites differentiate between Crohn's patients and non-IBD controls, showing a distinct signature within the biological samples of CD patients and their importance in pathophysiology of CD. Conclusion: This systematic review provides a comprehensive and categorical signature of dysregulated metabolites across biological samples and provide 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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