High-Resolution Metabolomics for Nutrition and Health Assessment of Armed Forces Personnel

Accardi, Carolyn Jonas; Walker, Douglas I.; Uppal, Karan; Quyyumi, Arshed A; Rohrbeck, Patricia; Pennell, Kurt D.; Mallon, Timothy M.; Jones, Dean P.

doi:10.1097/jom.0000000000000770

Cited by 36 publications

(25 citation statements)

References 49 publications

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“…Participant metabolic characteristics, derived from the metabolomics analysis of plasma, at baseline, were comparable to or within a range of previously reported values for selected features (Table 1) (50). In total, raw feature extractions yielded unique 9,377–10,583 features in both plasma and saliva, and 7,688–8,565 features in EBC.…”

Section: Resultssupporting

confidence: 81%

Metabolomic profiles of plasma, exhaled breath condensate, and saliva are correlated with potential for air toxics detection

et al. 2017

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Introduction Advances in the development of high-resolution metabolomics (HRM) have provided new opportunities for their use in characterizing exposures to environmental air pollutants and air pollution-related disease etiologies. Exposure assessment studies have considered blood, breath, and saliva as biological matrices suitable for measuring responses to air pollution exposures. The current study examines comparability among these three matrices using HRM and explored their potential for measuring mobile source air toxics. Methods Four participants provided saliva, exhaled breath concentrate (EBC), and plasma before and after a 2-hour road traffic exposure. Samples were analyzed on a Thermo Scientific QExactive MS system in positive electrospray ionization (ESI) mode and resolution of 70,000 FHWM with C18 chromatography. Data were processed using apLCMS and xMSanalyzer on the R statistical platform. Results The analysis yielded 7,110, 6,019, and 7,747 reproducible features in plasma, EBC, and saliva, respectively. Correlations were moderate-to-strong (R = 0.41 – 0.80) across all pairwise comparisons of feature intensity within profiles, with the strongest between EBC and saliva. The associations of mean intensities between matrix pairs were positive and significant, controlling for subject and sampling time effects. Six out of 20 features shared in all three matrices putatively matched a list of known mobile-source air toxics. Conclusions Plasma, saliva, and EBC have largely comparable metabolic profiles measurable through HRM. These matrices have the potential to be used in identification and measurement of exposures to mobile source air toxics, though further, targeted study is needed.

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Section: Resultssupporting

confidence: 81%

Metabolomic profiles of plasma, exhaled breath condensate, and saliva are correlated with potential for air toxics detection

et al. 2017

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“…Identities of selected plasma amino acids, metabolic intermediates, nutrition and clinical health indicators were verified by ion dissociation tandem mass spectrometry (MS/MS) and co-elution of standards (28–30). Metabolite concentrations were determined using reference standardization relative to pooled reference plasma calibrated to NIST SRM1950 (28,30).…”

Section: Methodsmentioning

confidence: 99%

“…Metabolite concentrations were determined using reference standardization relative to pooled reference plasma calibrated to NIST SRM1950 (28,30). Each metabolite concentration was calculated for each sample using the ion intensity and known concentration for the respective m/z in the pooled reference sample.…”

Section: Methodsmentioning

confidence: 99%

Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: A pilot randomized study of high-dose vitamin D 3 administration

et al. 2017

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Background Cystic fibrosis (CF) is a chronic catabolic disease often requiring hospitalization for acute episodes of worsening pulmonary exacerbations. Limited data suggest that vitamin D may have beneficial clinical effects, but the impact of vitamin D on systemic metabolism in this setting is unknown. Objective We used high-resolution metabolomics (HRM) to assess the impact of baseline vitamin D status and high-dose vitamin D3 administration on systemic metabolism in adults with CF with an acute pulmonary exacerbation. Design Twenty-five hospitalized adults with CF were enrolled in a randomized trial of high-dose vitamin D3 (250,000 IU vitamin D3 bolus) versus placebo. Age-matched healthy subjects served as a reference group for baseline comparisons. Plasma was analyzed with liquid chromatography/ultra-high resolution mass spectrometry. Using recent HRM bioinformatics and metabolic pathway enrichment methods, we examined associations with baseline vitamin D status (sufficient vs deficient per serum 25-hydroxyvitamin D concentrations) and the 7-day response to vitamin D3 supplementation. Results Several amino acids and lipid metabolites differed between CF and healthy control subjects, indicative of an overall catabolic state. In CF subjects, 343 metabolites differed (P<0.05) by baseline vitamin D status and were enriched within 7 metabolic pathways including fatty acid, amino acid, and carbohydrate metabolism. A total of 316 metabolites, which showed enrichment for 15 metabolic pathways--predominantly representing amino acid pathways-- differed between the vitamin D3- and placebo-treated CF subjects over time (P<0.05). In the placebo group, several tricarboxylic acid cycle intermediates increased while several amino acid-related metabolites decreased; in contrast, little change in these metabolites occurred with vitamin D3 treatment. Conclusions Numerous metabolic pathways detected by HRM varied in association with vitamin D status and high-dose vitamin D3 supplementation in adults with CF experiencing a pulmonary exacerbation. Overall, these pilot data suggest an anti-catabolic effect of high-dose vitamin D3 in this clinical setting.

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“…Electrospray ionization was used in the positive ion mode on the Q-Exactive HF mass spectrometer operating with resolution set to 120,000 and scan range set to 85–1275 m/z (mass to charge) (Liu et al, 2016; Soltow et al, 2013). Ultra-high resolution mass spectrometry operating at 60,000 and 120,000 resolution have previously been shown to provide effective quantification of metabolites in biologic extracts (Accardi et al, 2016; Go et al, 2015b, 2015c, 2015d; Johnson et al, 2008). A 2% formic acid/acetonitrile gradient was used as described (Liu et al, 2016).…”

Section: Methodsmentioning

confidence: 99%

“…However, these do not yet have sufficient theoretical or experimental development for application to nutritional assessment. For instance, high-resolution metabolomics (HRM) (Walker et al, 2016) supports both targeted analysis of nutrients (Accardi et al, 2016) and also targeted metabolome-wide association study (MWAS) to discover metabolites and metabolic pathways that vary in association with an essential nutrient (Go et al, 2015d). In principle, this 3-step approach [ 1) experimental variation in a nutrient, 2) targeted analysis of a metabolite expected to change and 3) MWAS of the targeted metabolite] provides a way to map out diverse metabolic networks associated with variation in specific nutrients.…”

Section: Introductionmentioning

confidence: 99%

Putrescine as indicator of manganese neurotoxicity: Dose-response study in human SH-SY5Y cells

Fernandes

Chandler

Liu

et al. 2018

Food and Chemical Toxicology

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Disrupted polyamine metabolism with elevated putrescine is associated with neuronal dysfunction. Manganese (Mn) is an essential nutrient that causes neurotoxicity in excess, but methods to evaluate biochemical responses to high Mn are limited. No information is available on dose-response effects of Mn on putrescine abundance and related polyamine metabolism. The present research was to test the hypothesis that Mn causes putrescine accumulation over a physiologically adequate to toxic concentration range in a neuronal cell line. We used human SH-SY5Y neuroblastoma cells treated with MnCl2 under conditions that resulted in cell death or no cell death after 48 h. Putrescine and other metabolites were analyzed by liquid chromatography-ultra high-resolution mass spectrometry. Putrescine-related pathway changes were identified with metabolome-wide association study (MWAS). Results show that Mn caused a dose-dependent increase in putrescine over a non-toxic to toxic concentration range. MWAS of putrescine showed positive correlations with the polyamine metabolite N8-acetylspermidine, methionine-related precursors, and arginine-associated urea cycle metabolites, while putrescine was negatively correlated with γ-aminobutyric acid (GABA)-related and succinate-related metabolites (P < 0.001, FDR < 0.01). These data suggest that measurement of putrescine and correlated metabolites may be useful to study effects of Mn intake in the high adequate to UL range.

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High-Resolution Metabolomics for Nutrition and Health Assessment of Armed Forces Personnel

Abstract: HRM analysis of serum is suitable for real-time and/or retrospective evaluation of nutrition and health status of specific military cohorts.

Cited by 36 publications

References 49 publications

Metabolomic profiles of plasma, exhaled breath condensate, and saliva are correlated with potential for air toxics detection

Metabolomic profiles of plasma, exhaled breath condensate, and saliva are correlated with potential for air toxics detection

Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: A pilot randomized study of high-dose vitamin D 3 administration

Putrescine as indicator of manganese neurotoxicity: Dose-response study in human SH-SY5Y cells

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