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Abstract
Inflammatory bowel disease (IBD) has stimulated much interest due to its surging incidences and health impacts in the U.S. and worldwide. However, the exact cause of IBD remains incompletely understood, and biomarker is lacking towards early diagnostics and effective therapy assessment. To tackle these, the emerging high-resolution mass spectrometry (HRMS)-based metabolomics shows promise. Here, we conducted a pilot untargeted LC/MS metabolomic profiling in Crohn’s disease, for which serum samples of both active and inactive cases were collected, extracted, and profiled by a state-of-the-art compound identification workflow. Results show a distinct metabolic profile of Crohn’s from control, with most metabolites downregulated. The identified compounds are structurally diverse, pointing to important pathway perturbations ranging from energy metabolism (e.g., β-oxidation of fatty acids) to signaling cascades of lipids (e.g., DHA) and amino acid (e.g., L-tryptophan). Importantly, an integral role of gut microbiota in the pathogenesis of Crohn’s disease is highlighted. Xenobiotics and their biotransformants were widely detected, calling for massive exposomic profiling for future cohort studies as such. This study endorses the analytical capacity of untargeted metabolomics for biomarker development, cohort stratification, and mechanistic interpretation; the findings might be valuable for advancing biomarker research and etiologic inquiry in IBD.
Highlights
The inflammatory bowel diseases (IBD) Crohn’s disease and ulcerative colitis (UC) are common, relapsing, and inflammatory disorders of the gastrointestinal (GI) tract, resulting in abdominal pain, diarrhea, internal bleeding, and many other complications [1,2]
Molecules 2018, 23, x from amino acids, lipids, nucleosides, to novel exogenous bio-transformants. This structural diversity endorses the analytical capacity of untargeted metabolomics as a guiding tool for etiologic inquiry for Crohn’s, but it highlights a challenge to resolving the metabolic complexity of pathological changes pertaining to intestinal inflammation
Integrated pathway analysis further identification procedures unravels a diverse collection of metabolites to explore, ranging from amino identifies metabolic pathways in response to Crohn’s, spanning bioenergetics
Summary
The inflammatory bowel diseases (IBD) Crohn’s disease and ulcerative colitis (UC) are common, relapsing, and inflammatory disorders of the gastrointestinal (GI) tract, resulting in abdominal pain, diarrhea, internal bleeding, and many other complications [1,2]. Crohn’s disease can impact any part of the GI tract, starting often with small intestine, whereas UC’s damage is limited to colon and rectum. Molecules 2019, 24, 449 understood, though it is accepted that genetics, the immune system, and environmental factors all play a role [5,6,7]. Each individual mutation adds to the risk and degree of inflammation, mainly via their impacts on the immune system. Evidence from in vivo and in vitro models supports that a dysregulated immune response against commensal intestinal microbiota is responsible for the onset of IBD, in genetically susceptible individuals [9,10,11]. There are dominant environmental components to the pathogenesis of IBD as well [7]; one notable and most thoroughly documented example is smoking, which seems interestingly favorable in UC subjects, but exacerbates the progression of Crohn’s [12]
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