Metabolomics of Inflammatory Bowel Disease in African American Patients
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Gray, Jada Simone
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Abstract
Inflammatory Bowel Disease (IBD) in African American (AA) and individuals of European Ancestry (EA) is steadily growing. Unfortunately, IBD studies underrepresent AA, compromising our understanding of disease etiology and progression in the subpopulation. IBD affects 96 of 100,000 AA every year, so generation of numerous well-balanced and matched biospecimens for metabolomic studies is challenging. Metabolomics provides the most immediate snapshot of the IBD phenotype, showing contrasting pathogenesis in AA vs. EA individuals. We here present a new Dynamic SQUAD approach where LC-MS experiments are performed in a sequential fashion as more biospecimens become available. This approach builds a targeted metabolite panel that reflects IBD pathway alterations from the non-targeted data block produced by the previous SQUAD LC-MS batch. We conducted SQUAD LC-MS experiments on biopsies from IBD patients to measure targeted and non-targeted data for different analytes using a Thermo ID-X tribrid mass spectrometer. A literature metanalysis indicated specific metabolic reactions that can differentiate Crohn’s disease (CD) from healthy patients. Pathways altered included amino acid metabolism, tryptophan metabolism, microbial metabolism, and energy metabolism, indicating dysbiosis of the gut microbiome, showing a decrease in the diversity of microbes/metabolites in the gut1. Additionally, metabolic modeling indicated that inflamed CD patient ileal tissue displays a distinct metabolic signature compared with non-inflamed tissue2. Subsequently, we sought to experimentally confirm whether the CD ileum contained metabolic changes versus controls using non-targeted LC-MS of a small external pilot cohort, complementary to in silico metabolic modeling to characterize whether the changes in metabolic pathways correlate to specific changes in specific lipids and/or metabolite composition. The top discriminant analytes were also added to the first targeted SQUAD panel. These ongoing studies will help us probe metabolomics alterations in the mucosal tissue to further our insights on IBD differences across populations.
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2024-11-20
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