Cargando…

Serum Metabolomics Identifies Altered Bioenergetics, Signaling Cascades in Parallel with Exposome Markers in Crohn’s Disease

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 th...

Descripción completa

Detalles Bibliográficos
Autores principales: Lai, Yunjia, Xue, Jingchuan, Liu, Chih-Wei, Gao, Bei, Chi, Liang, Tu, Pengcheng, Lu, Kun, Ru, Hongyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385106/
https://www.ncbi.nlm.nih.gov/pubmed/30691236
http://dx.doi.org/10.3390/molecules24030449
_version_ 1783397129018933248
author Lai, Yunjia
Xue, Jingchuan
Liu, Chih-Wei
Gao, Bei
Chi, Liang
Tu, Pengcheng
Lu, Kun
Ru, Hongyu
author_facet Lai, Yunjia
Xue, Jingchuan
Liu, Chih-Wei
Gao, Bei
Chi, Liang
Tu, Pengcheng
Lu, Kun
Ru, Hongyu
author_sort Lai, Yunjia
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6385106
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-63851062019-02-23 Serum Metabolomics Identifies Altered Bioenergetics, Signaling Cascades in Parallel with Exposome Markers in Crohn’s Disease Lai, Yunjia Xue, Jingchuan Liu, Chih-Wei Gao, Bei Chi, Liang Tu, Pengcheng Lu, Kun Ru, Hongyu Molecules Article 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. MDPI 2019-01-27 /pmc/articles/PMC6385106/ /pubmed/30691236 http://dx.doi.org/10.3390/molecules24030449 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lai, Yunjia
Xue, Jingchuan
Liu, Chih-Wei
Gao, Bei
Chi, Liang
Tu, Pengcheng
Lu, Kun
Ru, Hongyu
Serum Metabolomics Identifies Altered Bioenergetics, Signaling Cascades in Parallel with Exposome Markers in Crohn’s Disease
title Serum Metabolomics Identifies Altered Bioenergetics, Signaling Cascades in Parallel with Exposome Markers in Crohn’s Disease
title_full Serum Metabolomics Identifies Altered Bioenergetics, Signaling Cascades in Parallel with Exposome Markers in Crohn’s Disease
title_fullStr Serum Metabolomics Identifies Altered Bioenergetics, Signaling Cascades in Parallel with Exposome Markers in Crohn’s Disease
title_full_unstemmed Serum Metabolomics Identifies Altered Bioenergetics, Signaling Cascades in Parallel with Exposome Markers in Crohn’s Disease
title_short Serum Metabolomics Identifies Altered Bioenergetics, Signaling Cascades in Parallel with Exposome Markers in Crohn’s Disease
title_sort serum metabolomics identifies altered bioenergetics, signaling cascades in parallel with exposome markers in crohn’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385106/
https://www.ncbi.nlm.nih.gov/pubmed/30691236
http://dx.doi.org/10.3390/molecules24030449
work_keys_str_mv AT laiyunjia serummetabolomicsidentifiesalteredbioenergeticssignalingcascadesinparallelwithexposomemarkersincrohnsdisease
AT xuejingchuan serummetabolomicsidentifiesalteredbioenergeticssignalingcascadesinparallelwithexposomemarkersincrohnsdisease
AT liuchihwei serummetabolomicsidentifiesalteredbioenergeticssignalingcascadesinparallelwithexposomemarkersincrohnsdisease
AT gaobei serummetabolomicsidentifiesalteredbioenergeticssignalingcascadesinparallelwithexposomemarkersincrohnsdisease
AT chiliang serummetabolomicsidentifiesalteredbioenergeticssignalingcascadesinparallelwithexposomemarkersincrohnsdisease
AT tupengcheng serummetabolomicsidentifiesalteredbioenergeticssignalingcascadesinparallelwithexposomemarkersincrohnsdisease
AT lukun serummetabolomicsidentifiesalteredbioenergeticssignalingcascadesinparallelwithexposomemarkersincrohnsdisease
AT ruhongyu serummetabolomicsidentifiesalteredbioenergeticssignalingcascadesinparallelwithexposomemarkersincrohnsdisease