Development of an Accurate Mass Retention Time Database for Untargeted Metabolomic Analysis and Its Application to Plasma and Urine Pediatric Samples.
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ABSTRACT:
SUBMITTER: Lavarello C
PROVIDER: S-EPMC8303579 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Eicosapentaenoic acid (EPA) and ?-lipoic acid (?-LA) have been investigated for their beneficial effects on obesity and cardiovascular risk factors. In the current research, the goal was to evaluate metabolomic changes following the dietary supplementation of these two lipids, alone or combined in healthy overweight/obese sedentary women following an energy-restricted diet. For this purpose, an untargeted metabolomics approach was conducted on urine samples using liquid chromatography coupled with time of flight mass spectrometry (HPLC-TOF-MS).This is a short-term double blind placebo-controlled study with a parallel nutritional design that lasted 10 weeks. Participants were assigned to one of the 4 experimental groups [Control, EPA (1.3 g/d), ?-LA (0.3 g/d) and EPA+?-LA (1.3 g/d?+?0.3 g/d)]. All intervention groups followed an energy-restricted diet of 30% less than total energy expenditure. Clinically relevant biochemical measurements were analyzed. Urine samples (24 h) were collected at baseline and after 10 weeks. Untargeted metabolomic analysis on urine samples was carried out, and principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were performed for the pattern recognition and characteristic metabolites identification.Urine samples were scattered in the PCA scores plots in response to the supplementation with ?-LA. Totally, 28 putative discriminant metabolites in positive ionization, and 6 in negative ionization were identified among groups clearly differentiated according to the ?-LA administration. Remarkably is the presence of an ascorbate intermediate metabolite (one of the isomers of trihydroxy-dioxohexanoate, or dihydroxy-oxohexanedionate) in the groups supplemented with ?-LA. This fact might be associated with antioxidant properties of both ?-LA and ascorbic acid. Correlations between phenotypical parameters and putative metabolites of provided additional information on whether there is a direct or inverse relationship between them. Especially interesting are the negative correlation between ascorbate intermediate metabolite and asymmetric dimethylarginine (ADMA) and the positive one between superoxide dismutase (SOD) and ?-LA supplementation.This metabolomic approach supports that the beneficial effects of ?-LA administration on body weight reduction may be partly explained by the antioxidant properties of this organosulfur carboxylic acid mediated by isomers of trihydroxy-dioxohexanoate, or dihydroxy-oxohexanedionate.Clinicaltrials.gov NCT01138774 .
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Project description:Chronic hepatic disease can present a diagnostic challenge with different etiologies being associated with similar clinical and laboratory findings. The histopathological assessment of a liver biopsy specimen is usually required in order to make a definitive diagnosis and the availability of non-invasive prognostic biomarkers is limited. The emerging science of metabolomics is used to detect changes in endogenous low molecular weight metabolites in biological samples and offers the possibility of identifying noninvasive markers of disease. The objective of this study was to investigate differences in the urine metabolome between healthy dogs, dogs with chronic hepatitis, dogs with hepatocellular carcinoma, and dogs with a congenital portosystemic shunt. Stored urine samples from 10 healthy dogs, 10 dogs with chronic hepatitis, 6 dogs with hepatocellular carcinoma, and 5 dogs with a congenital portosystemic shunt were analyzed. The urine metabolome was analyzed by gas chromatography-quadrupole time of flight mass spectrometry and 220 known metabolites were identified. Principal component analysis and heat dendrogram plots of the metabolomics data showed clustering between groups. Random forest analysis showed differences in the abundance of various metabolites including putrescine, gluconic acid, sorbitol, and valine. Based on univariate statistics, 37 metabolites were significantly different between groups. In, conclusion, the urine metabolome varies between healthy dogs, dogs with chronic hepatitis, dogs with hepatocellular carcinoma, and dogs with a congenital portosystemic shunt. Further targeted assessment of these metabolites is needed to assess their diagnostic utility.
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Project description:BACKGROUND:To discover biomarker panels that could distinguish cancers (BC and RCC) from healthy controls (HCs) and bladder cancers (BC) from renal cell carcinoma (RCC), regardless of whether the patients have haematuria. In addition, we also explored the altered metabolomic pathways of BC and RCC. METHODS:In total, 403 participants were enrolled in our study, which included 146?BC patients (77 without haematuria and 69 with haematuria), 115 RCC patients (94 without haematuria and 21 with haematuria) and 142 sex- and age-matched HCs. Their midstream urine samples were collected and analysed by performing UPLC-MS. The statistical methods and pathway analyses were applied to discover potential biomarker panels and altered metabolic pathways. RESULTS:The panel of ?-CEHC, ?-cortolone, deoxyinosine, flunisolide, 11b,17a,21-trihydroxypreg-nenolone and glycerol tripropanoate could distinguish the patients with cancer from the HCs (the AUC was 0.950) and the external validation also displayed a good predictive ability (the AUC was 0.867). The panel of 4-ethoxymethylphenol, prostaglandin F2b, thromboxane B3, hydroxybutyrylcarnitine, 3-hydroxyphloretin and N'-formylkynurenine could differentiate BC from RCC without haematuria. The AUC was 0.829 in the discovering group and 0.76 in the external validation. The metabolite panel comprising 1-hydroxy-2-oxopropyl tetrahydropterin, 1-acetoxy-2-hydroxy-16-heptadecyn-4-one, 1,2-dehydrosalsolinol and L-tyrosine could significantly discriminate BC from RCC with haematuria (AUC was 0.913). Pathway analyses revealed altered lipid and purine metabolisms between cancer patients and HCs, together with disordered amino acid and purine metabolisms between BC and RCC with haematuria. CONCLUSIONS:UPLC-MS urine metabolomic analyses could not only differentiate cancers from HCs but also discriminate BC from RCC. In addition, pathway analyses demonstrated a deeper metabolic mechanism of BC and RCC.
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Project description:OBJECTIVE:Patients with CAD have substantial residual risk of mortality, and whether hitherto unknown small-molecule metabolites and metabolic pathways contribute to this risk is unclear. We sought to determine the predictive value of plasma metabolomic profiling in patients with CAD. APPROACH AND RESULTS:Untargeted high-resolution plasma metabolomic profiling of subjects undergoing coronary angiography was performed using liquid chromatography/mass spectrometry. Metabolic features and pathways associated with mortality were identified in 454 subjects using metabolome-wide association studies and Mummichog, respectively, and validated in 322 subjects. A metabolomic risk score comprising of log-transformed HR estimates of metabolites that associated with mortality and passed LASSO regression was created and its performance validated. In 776 subjects (66.8 years, 64% male, 17% Black), 433 and 357 features associated with mortality (FDR-adjusted q<0.20); and clustered into 21 and 9 metabolic pathways in first and second cohorts, respectively. Six pathways (urea cycle/amino group, tryptophan, aspartate/asparagine, lysine, tyrosine, and carnitine shuttle) were common. A metabolomic risk score comprising of 7 metabolites independently predicted mortality in the second cohort (HR per 1-unit increase 2.14, 95%CI 1.62, 2.83). Adding the score to a model of clinical predictors improved risk discrimination (delta C-statistic 0.039, 95%CI -0.006, 0.086; and Integrated Discrimination Index 0.084, 95%CI 0.030, 0.151) and reclassification (continuous Net Reclassification Index 23.3%, 95%CI 7.9%, 38.2%). CONCLUSIONS:Differential regulation of six metabolic pathways involved in myocardial energetics and systemic inflammation is independently associated with mortality in patients with CAD. A novel risk score consisting of representative metabolites is highly predictive of mortality.
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Project description:Phthalates are known endocrine disruptors and found in almost all people with several associated adverse health outcomes reported in humans and animal models. Limited data are available on the relationship between exposure to endocrine disrupting chemicals and the human metabolome. We examined the relationship of metabolomic profiles in plasma and urine of 115 pregnant women with eleven urine phthalate metabolites measured at 26 weeks of gestation to identify potential biomarkers and relevant pathways. Targeted metabolomics was performed by selected reaction monitoring liquid chromatography and triple quadrupole mass spectrometry to measure 415 metabolites in plasma and 151 metabolites in urine samples. We have chosen metabolites with the best defined peaks for more detailed analysis (138 in plasma and 40 in urine). Relationship between urine phthalate metabolites and concurrent metabolomic markers in plasma and urine suggested potential involvement of diverse pathways including lipid, steroid, and nucleic acid metabolism and enhanced inflammatory response. Most of the correlations were positive for both urine and plasma, and further confirmed by regression and PCA analysis. However, after the FDR adjustment for multiple comparisons, only 9 urine associations remained statistically significant (q-values 0.0001-0.0451), including Nicotinamide mononucleotide, Cysteine T2, Cystine, and L-Aspartic acid. Additionally, we found negative associations of maternal pre-pregnancy body mass index (BMI) with more than 20 metabolomic markers related to lipid and amino-acid metabolism and inflammation pathways in plasma (p = 0.01-0.0004), while Mevalonic acid was positively associated (p = 0.009). Nicotinic acid, the only significant metabolite in urine, had a positive association with maternal BMI (p = 0.002). In summary, when evaluated in the context of metabolic pathways, the findings suggest enhanced lipid biogenesis, inflammation and altered nucleic acid metabolism in association with higher phthalate levels. These results provide new insights into the relationship between phthalates, common in most human populations, and metabolomics, a novel approach to exposure and health biomonitoring.
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