Document Type
Conference Proceeding
Publication Date
6-2024
Abstract
Crohn’s disease (CD) is a heterogeneous and multifactorial inflammatory bowel disease with a significant global health impact. Genetic and lifestyle factors contribute to its etiology, emphasizing dysregulation of intestinal and dietary habits. Our study aimed to identify fecal metabolites from treatment-naïve, pediatric sufferers of CD, which allowed us to investigate the underlying biochemical perturbations associated with the disease, highlighting potential, translational targets. Using a Waters Acquity UPLC coupled with a Xevo-TQ-S mass spectrometer, we quantified >500 metabolites in fecal samples (n=72) of pediatric CD sufferers. We developed diagnostic tests capable of accurately discriminating between children with CD and healthy individuals using artificial intelligence platforms. A total of 243 significantly altered (FDR q < 0.05) metabolites distinguished HC from CD. The top six metabolites are methionine, serotonin, Cer(d18:1/24:1), CE (20:3), p-Cresol-SO4, and Hex2Cer(d18:1/16:0). The top 5 predictive models all performed strongly with accuracy ranging from 90-97%, AUC-ROC (90-98%), with sensitivity and specificity values ranging from 88-95% and 90-100%, respectively. We identified several metabolic pathways that were significantly perturbed in those individuals with CD. The top 5 pathways include Sphingolipid, Methionine, Fatty acid, Betaine, and Arachidonic Acid metabolism, which all contribute to inflammation, immune dysregulation, and intestinal barrier dysfunction. Dysregulation of these metabolic cascades has been consistently reported in CD. Our study emphasizes the significance of exploring sphingolipid metabolism and understanding the intricate interaction between energy homeostasis in gut microbial compositions. Early nutrition and the introduction of solid foods exert significant influence on the intestinal microbiome, with breastmilk immunoglobulins providing protective benefits against enteric infections, thereby maintaining microbiome health. Therefore, a comprehensive multi-omics investigation involving a larger cohort of pediatric CD individuals is essential to unravel the complexities of metabolites and host-microbiome interactions. Further research aims to comprehend disease progression, identify therapeutic avenues, explore preventive strategies, improve biomarker identification, and tailor treatments.
Recommended Citation
Ashrafi N, Yilmaz A, Monacelli N, Callahan RE, Ustun Ilyas, Novotny NM, et al. [Graham S]. Insights from targeted fecal metabolomic analysis reveal altered metabolic pathways in treatment-naive pediatric subjects with Crohn's disease. Presented at: 20th Annual Conference of the Metabolomics Society; 2024 Jun 16-20; Osaka, Japan.
Comments
20th Annual Conference of the Metabolomics Society, June 16-20, 2024, Osaka, Japan