Metabolomics Reveals Altered Metabolic Pathways in Experimental Asthma

Ho, Wanxing Eugene; Xu, Yong‐Jiang; Xu, Fengguo; Chang, Cheng; Peh, Hong Yong; Tannenbaum, Steven R.; Wong, W.S. Fred; Ong, Choon Nam

doi:10.1165/rcmb.2012-0246oc

Cited by 85 publications

(90 citation statements)

References 33 publications

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“…32 Citrate, creatine and creatinine are three metabolites that were also found to be increased in ARDS plasma samples by 1D- 1 H-NMR. 9, 26 The remainder of the identified metabolites were specific to BALF.…”

Section: Discussionmentioning

confidence: 96%

Untargeted LC–MS Metabolomics of Bronchoalveolar Lavage Fluid Differentiates Acute Respiratory Distress Syndrome from Health

et al. 2013

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Acute respiratory distress syndrome (ARDS) remains a significant hazard to human health and is clinically challenging because there are no prognostic biomarkers and no effective pharmacotherapy. The lung compartment metabolome may detail the status of the local environment that could be useful in ARDS biomarker discovery and the identification of drug target opportunities. However, neither the utility of bronchoalveolar lavage fluid (BALF) as a biofluid for metabolomics nor the optimal analytical platform for metabolite identification are established. To address this, we undertook a study to compare metabolites in BALF samples from patients with ARDS and healthy controls using a newly developed liquid chromatography (LC)-mass spectroscopy (MS) platform for untargeted metabolomics. Following initial testing of three different high performance liquid chromatography (HPLC) columns, we determined that reversed phase (RP)-LC and hydrophilic interaction chromatography (HILIC), were the most informative chromatographic methods because they yielded the most and highest quality data. Following confirmation of metabolite identification, statistical analysis resulted in 37 differentiating metabolites in the BALF of ARDS compared with health across both analytical platforms. Pathway analysis revealed networks associated with amino acid metabolism, glycolysis and gluconeogenesis, fatty acid biosynthesis, phospholipids and purine metabolism in the ARDS BALF. The complementary analytical platforms of RPLC and HILIC-LC generated informative, insightful metabolomics data of the ARDS lung environment.

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Section: Discussionmentioning

confidence: 96%

Untargeted LC–MS Metabolomics of Bronchoalveolar Lavage Fluid Differentiates Acute Respiratory Distress Syndrome from Health

et al. 2013

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“…Existing metabolomics that have studied allergic asthma have uncovered altered metabolism and metabolic profiles in serum, urine, and BALF samples from clinical and experimental asthma [40,41,42], but it has not directly investigated the relevant lung metabolome changes, which would provide novel insights into changes in lung metabolism under asthmatic conditions. Correspondingly, our recent study has used metabolomics to analyze the plasma from OVA-induced allergic asthma, and demonstrated that this approach could offer opportunities for disease-related biomarker and pathway discovery [21].…”

Section: Discussionmentioning

confidence: 99%

The Effect of Chinese Herbal Medicine Formula mKG on Allergic Asthma by Regulating Lung and Plasma Metabolic Alternations

Meng

Jia

et al. 2017

IJMS

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Asthma is a chronic inflammatory disorder of the airway and is characterized by airway remodeling, hyperresponsiveness, and shortness of breath. Modified Kushen Gancao Formula (mKG), derived from traditional Chinese herbal medicines (TCM), has been demonstrated to have good therapeutic effects on experimental allergic asthma. However, its anti-asthma mechanism remains currently unknown. In the present work, metabolomics studies of biochemical changes in the lung tissue and plasma of ovalbumin (OVA)-induced allergic asthma mice with mKG treatment were performed using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Partial least squares-discriminate analysis (PLS−DA) indicated that the metabolic perturbation induced by OVA was reduced after mKG treatment. A total of twenty-four metabolites involved in seven metabolic pathways were identified as potential biomarkers in the development of allergic asthma. Among them, myristic acid (L3 or P2), sphinganine (L6 or P4), and lysoPC(15:0) (L12 or P16) were detected both in lung tissue and plasma. Additionally, L-acetylcarnitine (L1), thromboxane B2 (L2), 10-HDoHE (L10), and 5-HETE (L11) were first reported to be potential biomarkers associated with allergic asthma. The treatment of mKG mediated all of those potential biomarkers except lysoPC(15:0) (P16). The anti-asthma mechanism of mKG can be achieved through the comprehensive regulation of multiple perturbed biomarkers and metabolic pathways.

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“…Levels of metabolites participating in the tricarboxylic acid cycle were altered in asthma, and fluctuations of metabolites in pathways involved in cellular energy metabolism in the lungs have been observed in mouse models of experimental asthma. 30 Potentially, alterations in these pathways may reflect the reduced ability of the damaged lung to meet the substantial energy demands of activated inflammatory cells in the allergic airway. Finally, epigenetic effects have a strong impact on asthma severity, and metabolites related to the methyl transfer pathway were also reported.…”

Section: Biological Insights Into Asthma Pathophysiology and Treatmentmentioning

confidence: 99%

Asthma Metabolomics and the Potential for Integrative Omics in Research and the Clinic

Kelly

Dahlin

McGeachie

et al. 2017

Chest

149

135

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Asthma is a complex disease well-suited to metabolomic profiling, both for the development of novel biomarkers and for the improved understanding of pathophysiology. In this review, we summarize the 21 existing metabolomic studies of asthma in humans, all of which reported significant findings and concluded that individual metabolites and metabolomic profiles measured in exhaled breath condensate, urine, plasma, and serum could identify people with asthma and asthma phenotypes with high discriminatory ability. There was considerable consistency across the studies in terms of the reported biomarkers, regardless of biospecimen, profiling technology, and population age. In particular, acetate, adenosine, alanine, hippurate, succinate, threonine, and trans-aconitate, and pathways relating to hypoxia response, oxidative stress, immunity, inflammation, lipid metabolism and the tricarboxylic acid cycle were all identified as significant in at least two studies. There were also a number of nonreplicated results; however, the literature is not yet sufficiently developed to determine whether these represent spurious findings or reflect the substantial heterogeneity and limited statistical power in the studies and their methods to date. This review highlights the need for additional asthma metabolomic studies to explore these issues, and, further, the need for standardized methods in the way these studies are conducted. We conclude by discussing the potential of translation of these metabolomic findings into clinically useful biomarkers and the crucial role that integrated omics is likely to play in this endeavor.CHEST 2017; 151(2):262-277

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Metabolomics Reveals Altered Metabolic Pathways in Experimental Asthma

Cited by 85 publications

References 33 publications

Untargeted LC–MS Metabolomics of Bronchoalveolar Lavage Fluid Differentiates Acute Respiratory Distress Syndrome from Health

Untargeted LC–MS Metabolomics of Bronchoalveolar Lavage Fluid Differentiates Acute Respiratory Distress Syndrome from Health

The Effect of Chinese Herbal Medicine Formula mKG on Allergic Asthma by Regulating Lung and Plasma Metabolic Alternations

Asthma Metabolomics and the Potential for Integrative Omics in Research and the Clinic

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