Serum metabolomics reveals pathways and biomarkers associated with asthma pathogenesis

Jung, Jeeyoun; Kim, S.-H.; Lee, H.-S.; Choi, Gil-Soon; Jung, Youngae; Ryu, Do Hyun; Park, Hae‐Sim; Hwang, Geum‐Sook

doi:10.1111/cea.12089

Cited by 145 publications

(176 citation statements)

References 40 publications

Supporting

Mentioning

150

Contrasting

Order By: Relevance

“…Another study by Jung et al [22] profiled the serum of asthmatic patients using NMR and showed an increase in succinate; however, glutamine was also shown to be increased, which is opposite of our results. Nevertheless, the increased TCA-cycle metabolism may suggest an enhanced requirement for energy due to the greater effort required to breathe during exacerbation and most likely is a response to hypoxic stress due to poor oxygenation.…”

Section: Discussioncontrasting

confidence: 99%

“…The TCA cycle is a series of enzymatic reactions that are used by aerobic organisms to generate energy and involves the oxidation of acetate derived from carbohydrates, fats or proteins. Succinate is an intermediate in this cycle and is greatly enriched in the asthma samples; this finding was consistent with previous reports of changes in the urine [8] or serum [22] of asthmatic patients by NMR-based metabolomics analysis. The study by Saude et al [8] showed that five metabolites acting in the TCA cycle (succinate, fumarate, oxaloacetate, cis-aconitate and 2 -oxoglutarate) were present at higher abundances in urine in asthmatic patients who had recently suffered an exacerbation.…”

Section: Discussionsupporting

confidence: 92%

“…It utilizes fundamental analytical techniques to probe the chemical fingerprint of the samples and makes use of multivariate statistical analyses to search for diseaserelated potential biomarkers and metabolic pathways [15][16][17][18] . To date, both nuclear magnetic resonance (NMR) [8,[19][20][21][22] and mass spectrometry (MS)-based [23,24] metabolomics techniques have been used to analyze respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD) and cystic fibrosis. However, studies have not documented specific metabolic alterations in the sera of asthmatic patients using gas chromatography mass spectrometry (GC-MS) methods.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Metabolic alterations in the sera of Chinese patients with mild persistent asthma: a GC-MS-based metabolomics analysis

Chang

Guo

et al. 2015

Acta Pharmacol Sin

View full text Add to dashboard Cite

Aim: To character the specific metabolomics profiles in the sera of Chinese patients with mild persistent asthma and to explore potential metabolic biomarkers. Methods: Seventeen Chinese patients with mild persistent asthma and age-and sex-matched healthy controls were enrolled. Serum samples were collected, and serum metabolites were analyzed using GC-MS coupled with a series of multivariate statistical analyses. Results: Clear intergroup separations existed between the asthmatic patients and control subjects. A list of differential metabolites and several top altered metabolic pathways were identified. The levels of succinate (an intermediate in tricarboxylic acid cycle) and inosine were highly upregulated in the asthmatic patients, suggesting a greater effort to breathe during exacerbation and hypoxic stress due to asthma. Other differential metabolites, such as 3,4-dihydroxybenzoic acid and phenylalanine, were also identified. Furthermore, the differential metabolites possessed higher values of area under the ROC curve (AUC), suggesting an excellent clinical ability for the prediction of asthma. Conclusion: Metabolic activity is significantly altered in the sera of Chinese patients with mild persistent asthma. The data might be helpful for identifying novel biomarkers and therapeutic targets for asthma.

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Metabolic alterations in the sera of Chinese patients with mild persistent asthma: a GC-MS-based metabolomics analysis

Chang

Guo

et al. 2015

Acta Pharmacol Sin

View full text Add to dashboard Cite

show abstract

“…Metabolomics refers to the global investigation of metabolites in biological systems (comparing normal to disease) (Xu et al 2014), and has been applied to allergic asthma to profile metabolic changes and identify disease biomarkers (Lara et al 2008;Ho et al 2013Ho et al , 2014bSaude et al 2009Saude et al , 2011Mattarucchi et al 2012;Jung et al 2013). We have recently uncovered novel disease-relevant metabolic changes in the bronchoalveolar lavage fluid (BALF) from experimental mouse asthma, which involved major losses of sugars with resultant increases in energy metabolites and reductions of sterols (Ho et al , 2014b.…”

Section: Introductionmentioning

confidence: 99%

Anti-malarial drug artesunate restores metabolic changes in experimental allergic asthma

et al. 2014

Metabolomics

View full text Add to dashboard Cite

The anti-malarial drug artesunate possesses anti-inflammatory and anti-oxidative actions in experimental asthma, comparable to corticosteroid. We hypothesized that artesunate may modulate disease-relevant metabolic alterations in allergic asthma. To explore metabolic profile changes induced by artesunate in allergic airway inflammation, we analysed bronchoalveolar lavage fluid (BALF) and serum from naïve and ovalbumininduced asthma mice treated with artesunate, using both gas and liquid chromatography-mass spectrometry metabolomics. Pharmacokinetics analyses of serum and lung tissues revealed that artesunate is rapidly converted into the active metabolite dihydroartemisinin. Artesunate effectively suppressed BALF total and differential counts, and repressed BALF Th2 cytokines, IL-17, IL-12(p40), MCP-1 and G-CSF levels. Artesunate had no effects on both BALF and serum metabolome in naïve mice. Artesunate promoted restoration of BALF sterols (cholesterol, cholic acid and cortol), phosphatidylcholines and carbohydrates (arabinose, mannose and galactose) and of serum 18-oxocortisol, galactose, glucose and glucouronic acid in asthma. Artesunate prevented OVA-induced increases in pro-inflammatory metabolites from arginine-proline metabolic pathway, particularly BALF levels of urea and alanine and serum levels of urea, proline, valine and homoserine. Multiple statistical correlation analyses revealed association between altered BALF and serum metabolites and inflammatory cytokines. Dexamethasone failed to reduce Wanxing Eugene Ho and Yong-Jiang Xu have contributed equally to this work.Electronic supplementary material The online version of this article (doi:10.1007/s11306-014-0699-x) contains supplementary material, which is available to authorized users. Metabolomics (2015) 11:380-390 DOI 10.1007 urea level and caused widespread changes in metabolites irrelevant to asthma development. Here we report the first metabolome profile of artesunate treatment in experimental asthma. Artesunate restored specific metabolic perturbations in airway inflammation, which correlated well with its anti-inflammatory actions. Our metabolomics findings further strengthen the therapeutic value of using artesunate to treat allergic asthma.

show abstract

“…The endotype of high F E NO asthmatics showed a higher level of taurocholate than that of low F E NO asthmatics [19]. A few serum metabolites, including choline and arginine, showed positive correlations with FEV 1 % values [20]. However, most metabolites to date are neither directly related to the pathogenesis of asthma nor easy to measure repeatedly in clinical practice.…”

Section: Discussionmentioning

confidence: 93%

Metabolomic analysis identifies potential diagnostic biomarkers for aspirin‐exacerbated respiratory disease

Ban

Cho

Kim

et al. 2016

Clin Experimental Allergy

Self Cite

View full text Add to dashboard Cite

SummaryBackground To date, there has been no reliable in vitro test to diagnose aspirin-exacerbated respiratory disease (AERD). Objective To investigate potential diagnostic biomarkers for AERD using metabolomic analysis. Methods An untargeted profile of serum from asthmatics in the first cohort (group 1) comprising 45 AERD, 44 patients with aspirin-tolerant asthma (ATA), and 28 normal controls was developed using the ultra-high-performance liquid chromatography (UHPLC)/QToF MS system. Metabolites that discriminate AERD from ATA were quantified in both serum and urine, which were collected before (baseline) and after the lysine-aspirin bronchoprovocation test (Lys-ASA BPT). The serum metabolites were validated in the second cohort (group 2) comprising 50 patients with AERD and 50 patients with ATA. Results A clear discrimination of metabolomes was found between patients with AERD and ATA. In group 1, serum levels of LTE 4 and LTE 4 /PGF 2 a ratio before and after the Lys-ASA BPT were significantly higher in patients with AERD than in patients with ATA (P < 0.05 for each), and urine baseline levels of these two metabolites were significantly higher in patients with AERD. Significant differences of serum metabolite levels between patients with AERD and ATA were replicated in group 2 (P < 0.05 for each). Moreover, serum baseline levels of LTE 4 and LTE 4 /PGF 2 a ratio discriminated AERD from ATA with 70.5%/71.6% sensitivity and 41.5%/62.8% specificity, respectively (AUC = 0.649 and 0.732, respectively P < 0.001 for each). Urine baseline LTE 4 levels were significantly correlated with the fall in FEV 1 % after the Lys-ASA BPT in patients with AERD (P = 0.008, r = 0.463). Conclusions and Clinical Relevance Serum metabolite level of LTE 4 and LTE 4 /PGF 2 a ratio was identified as potential in vitro diagnostic biomarkers for AERD using the UHPLC/QToF MS system, which were closely associated with major pathogenetic mechanisms underlying AERD.

show abstract

Serum metabolomics reveals pathways and biomarkers associated with asthma pathogenesis

Abstract: These data showed that (1)H-NMR-based metabolite profiling of serum may be useful for the effective diagnosis of asthma and a further understanding of its pathogenesis.

Cited by 145 publications

References 40 publications

Metabolic alterations in the sera of Chinese patients with mild persistent asthma: a GC-MS-based metabolomics analysis

Metabolic alterations in the sera of Chinese patients with mild persistent asthma: a GC-MS-based metabolomics analysis

Anti-malarial drug artesunate restores metabolic changes in experimental allergic asthma

Metabolomic analysis identifies potential diagnostic biomarkers for aspirin‐exacerbated respiratory disease

Contact Info

Product

Resources

About