Magnetic Resonance Metabolomics Research Articles

Vibrio alginolyticus infection induces coupled changes of bacterial community and metabolic phenotype in the gut of swimming crab

The emulsification disease of swimming crab Portunus trituberculatus is mainly caused by Vibrio alginolyticus. Gut microbiota is involved in the immunity and diseases of crustaceans. In this study, we integrated 16S rRNA gene sequencing and 1H nuclear magnetic resonance metabolomics techniques to determine the effects of V. alginolyticus infection on bacterial composition and metabolic phenotype in the gut of P. trituberculatus. The results showed that V. alginolyticus infection induced marked changes in the gut bacterial composition of P. trituberculatus, which seems to drive the gut bacterial community into a kind of diseased status. The sums of the relative abundance of these indicator bacteria such as Vibrionaceae and Pseudoalteromonadaceae could be used to predict the increased risk of emulsification disease occurrence in swimming crab. V. alginolyticus infection also caused marked changes in the gut metabolic phenotype of P. trituberculatus, highlighted by the significantly changed levels of maltose, glucose, AMP, and amino acids. Importantly, the gut indicator bacteria showed comprehensive correlations with these significantly changed gut metabolites, which revealing the contributions of gut bacteria in pathogenesis of gut metabolic disorders of swimming crab after V. alginolyticus infection. Overall, this study provides solid evidence that gut bacteria are involved in the occurrence and development of crab vibriosis, which could be great important for gaining new insights into the pathogenesis mechanisms of emulsification disease and developing novel strategies for emulsification disease prevention of swimming crab.

Metabolite quantification of faecal extracts from colorectal cancer patients and healthy controls.

Colorectal cancer (CRC), a primary cause of morbidity and mortality worldwide is expected to rise in the coming years. A better understanding of the metabolic changes taking place during the disease progression is needed for effective improvements of screening strategies and treatments. In the present study, Nuclear Magnetic Resonance (NMR) metabolomics was used to quantify the absolute concentrations of metabolites in faecal extracts from two cohorts of CRC patients and healthy controls. The quantification of over 80 compounds revealed that patients with CRC had increased faecal concentrations of branched chain fatty acids (BCFA), isovalerate and isobutyrate plus valerate and phenylacetate but diminished concentrations of amino acids, sugars, methanol and bile acids (deoxycholate, lithodeoxycholate and cholate). These results suggest that alterations in microbial activity and composition could have triggered an increase in utilisation of host intestinal slough cells and mucins and led to an increase in BCFA, valerate and phenylacetate. Concurrently, a general reduction in the microbial metabolic function may have led to reduced levels of other components (amino acids, sugars and bile acids) normally produced under healthy conditions. This study provides a thorough listing of the most abundant compounds found in human faecal waters and presents a template for absolute quantification of metabolites. The production of BCFA and phenylacetate in colonic carcinogenesis warrants further investigations.

1 H-NMR metabolomics for evaluating the protective effect of Clinacanthus nutans (Burm. f) Lindau water extract against nitric oxide production in LPS-IFN-γ activated RAW 264.7 macrophages.

Clinacanthus nutans, a small shrub that is native to Southeast Asia, is commonly used in traditional herbal medicine and as a food source. Its anti-inflammation properties is influenced by the metabolites composition, which can be determined by different binary extraction solvent ratio and extraction methods used during plant post-harvesting stage. Evaluate the relationship between the chemical composition of C. nutans and its anti-inflammatory properties using nuclear magnetic resonance (NMR) metabolomics approach. The anti-inflammatory effect of C. nutans air-dried leaves extracted using five different binary extraction solvent ratio and two extraction methods was determined based on their nitric oxide (NO) inhibition effect in lipopolysaccharide-interferon-gamma (LPS-IFN-γ) activated RAW 264.7 macrophages. The relationship between extract bioactivity and metabolite profiles and quantifications were established using 1 H-NMR metabolomics and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The possible metabolite biosynthesis pathway was constructed to further strengthen the findings. Water and sonication prepared air-dried leaves possessed the highest NO inhibition activity (IC50 =190.43±12.26μg/mL, P<0.05). A total of 56 metabolites were tentatively identified using 1 H-NMR metabolomics. A partial least square (PLS) biplot suggested that sulphur containing glucoside, sulphur containing compounds, phytosterols, triterpenoids, flavones and some organic and amino acids were among the potential NO inhibitors. LC-MS/MS targeted quantification further supported sonicated water extract was among the extract that possessed the most abundant C-glycosyl flavones. The present study may serve as a preliminary reference for the selection of optimum extract in further C. nutans in vivo anti-inflammatory study.

Detecting biomarkers of musculoskeletal injury in racing Thoroughbreds with nuclear magnetic resonance metabolomics

Detecting biomarkers of musculoskeletal injury in racing Thoroughbreds with nuclear magnetic resonance metabolomics

Killing method affects the browning and the quality of the protein fraction of Black Soldier Fly (Hermetia illucens) prepupae: a metabolomics and proteomic insight

Insects are being explored as novel protein sources in order to overcome the future food demands connected to world growing population. Insects for food/feed uses are currently slowly killed through freezing by most insect rearing companies, and typically, enzymatic browning takes place in the insect proteins fractions. However, very little is known about the influence of these enzymatic reactions on the protein physical, chemical, nutritional and technological properties. In this work a metabolomics and proteomic study was conducted on Black Soldier Fly (Hermetia illucens) prepupae, killed by two different methods: freezing (commonly used), and blanching (with the aim to inhibit the enzymatic activities). Proton nuclear magnetic resonance (1H NMR) metabolomics demonstrated that slow killing method by freezing, compared with blanching, elicits the activation of several enzymatic pathways, among them melanisation with tyrosine consumption, energetic metabolism and lipolysis. These metabolic changes have an impact also on protein nutritional quality, with a loss of cysteine and lysine, likely involved in the process of melanisation and enzymatic browning. A strong effect was also observed on protein extractability: proteins from prepupae killed by blanching were found to be more extractable in milder conditions by chemical methods, and more prone to enzymatic digestion (97% of proteins released in solution upon proteolysis) than proteins from prepupae killed by freezing. All these data indicate that killing by blanching inhibits the browning reaction and other enzymatic changes occurring during slow killing by freezing, increasing the extractability of proteins in aqueous solutions, avoiding essential amino acid loss, and improving enzymatic digestibility.

Metabolomics studies on corticosterone-induced PC12 cells: A strategy for evaluating an in vitro depression model and revealing the metabolic regulation mechanism

There are three types of differentiated (un-, poorly- and well-differentiated) PC12 cells, which have been widely used as a model system for depression studies after the administration of corticosterone (CORT). In order to investigate the underlying metabolic profiles of CORT-induced PC12 cells and evaluate the suitable differentiated types of PC12 cells for use in depressive studies, proton nuclear magnetic resonance (1H NMR) metabolomics coupled with network analysis approaches were employed. The results showed that CORT induced metabolic alterations in PC12 cells. There were 8 and 13 common differential metabolites in intracellular and extracellular extracts, respectively, of the three types of differentiated PC12 cells in response to CORT treatment, and the perturbed metabolic pathways were involved in amino acid metabolism, glutathione metabolism, pyruvate metabolism and inositol phosphate metabolism. Eighteen protein targets of depression were identified from the five different metabolic pathways from metabolomics and network analysis among the three types of CORT-induced differentiated PC12 cells, and these proteins were all found in the pathways that were perturbed by CORT treatment of poorly-differentiated PC12 cells. These results may indicate that the metabolism of CORT-induced PC12 cells is similar to the pathogenesis of depression, and poorly-differentiated PC12 cells are the most suitable cells for depressive research among the distinct types of differentiated PC12 cells. Thus, an effective predicative strategy to evaluate the in vitro disease models could be referenced.

Rifampin- or Capreomycin-Induced Remodeling of the Mycobacterium smegmatis Mycolic Acid Layer Is Mitigated in Synergistic Combinations with Cationic Antimicrobial Peptides.

The mycobacterial cell wall affords natural resistance to antibiotics. Antimicrobial peptides (AMPs) modify the surface properties of mycobacteria and can act synergistically with antibiotics from differing classes. Here, we investigate the response of Mycobacterium smegmatis to the presence of rifampin or capreomycin, either alone or in combination with two synthetic, cationic, α-helical AMPs that are distinguished by the presence (D-LAK120-HP13) or absence (D-LAK120-A) of a kink-inducing proline. Using a combination of high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) metabolomics, diphenylhexatriene (DPH) fluorescence anisotropy measurements, and laurdan emission spectroscopy, we show that M.smegmatis responds to challenge with rifampin or capreomycin by substantially altering its metabolism and, in particular, by remodeling the cell envelope. Overall, the changes are consistent with a reduction of trehalose dimycolate and an increase of trehalose monomycolate and are associated with increased rigidity of the mycolic acid layer observed following challenge by capreomycin but not rifampin. Challenge with D-LAK120-A or D-LAK120-HP13 induced no or modest changes, respectively, in mycomembrane metabolites and did not induce a significant increase in the rigidity of the mycolic acid layer. Furthermore, the response to rifampin or capreomycin was significantly reduced when these were combined with D-LAK120-HP13 and D-LAK120-A, respectively, suggesting a possible mechanism for the synergy of these combinations. The remodeling of the mycomembrane in M.smegmatis is therefore identified as an important countermeasure deployed against rifampin or capreomycin, but this can be mitigated and the efficacy of rifampin or capreomycin potentiated by combining the drug with AMPs.IMPORTANCE We have used a combined NMR metabolomics/biophysical approach to better understand differences in the mechanisms of two closely related antimicrobial peptides, as well as the response of the model organism Mycobacterium smegmatis to challenge with first- or second-line antibiotics used against mycobacterial pathogens. We show that, in addition to membrane damage, the triggering of oxidative stress may be an important part of the mechanism of action of one AMP. The metabolic shift that accompanied rifampin and, particularly, capreomycin challenge was associated with modest and more dramatic changes, respectively, in the mycomembrane, providing a rationale for how the response to one antibiotic may affect bacterial penetration and, hence, the action of another. This study presents the first insights into how antimicrobial peptides may operate synergistically with existing antibiotics whose efficacy is waning or sensitize MDR mycobacteria and/or latent mycobacterial infections to them, prolonging the useful life of these drugs.

Plasma Nuclear Magnetic Resonance Metabolomics Discriminates Between High and Low Endoscopic Activity and Predicts Progression in a Prospective Cohort of Patients With Ulcerative Colitis.

Background and AimsEndoscopic assessment of ulcerative colitis [UC] is one of the most accurate measures of disease activity, but frequent endoscopic investigations are disliked by patients and expensive for the healthcare system. A minimally invasive test that provides a surrogate measure of endoscopic activity is required.MethodsPlasma nuclear magnetic resonance [NMR] spectra from 40 patients with UC followed prospectively over 6 months were analysed with multivariate statistics. NMR metabolite profiles were compared with endoscopic [Ulcerative Colitis Endoscopic Index of Severity: UCEIS], histological [Nancy Index] and clinical [Simple Clinical Colitis Activity Index: SCCAI] severity indices, along with routine blood measurements.ResultsA blinded principal component analysis spontaneously separated metabolite profiles of patients with low [≤3] and high [>3] UCEIS. Orthogonal partial least squares discrimination analysis identified low and high UCEIS metabolite profiles with an accuracy of 77 ± 5%. Plasma metabolites driving discrimination included decreases in lipoproteins and increases in isoleucine, valine, glucose and myo-inositol in high compared to low UCEIS. This same metabolite profile distinguished between low [Nancy 0–1] and high histological activity [Nancy 3–4] with a modest although significant accuracy [65 ± 6%] but was independent of SCCAI and all blood parameters measured. A different metabolite profile, dominated by changes in lysine, histidine, phenylalanine and tyrosine, distinguished between improvement in UCEIS [decrease ≥1] and worsening [increase ≥1] over 6 months with an accuracy of 74 ± 4%.ConclusionPlasma NMR metabolite analysis has the potential to provide a low-cost, minimally invasive technique that may be a surrogate for endoscopic assessment, with predictive capacity.

Circulating Metabolites and the Risk of Type 2 Diabetes—A Prospective Study of 10,938 Young Adults from Four Finnish Cohorts

Background: Advances in metabolomics have allowed high-throughput metabolic profiling of large population samples. We aimed to identify circulating lipids and metabolites predictive of the risk for type 2 diabetes in young adults. Methods: Nuclear magnetic resonance metabolomics was used to quantify 229 metabolic measures in 10,938 individuals from four Finnish cohorts (mean age 35 years, range 24-45). Associations between baseline metabolites and diabetes onset during 7-15 years of follow-up (330 incident cases) were assessed by logistic regression adjusted for sex, baseline age and glucose. Findings: Out of 229 metabolic measures, 174 were associated with risk for incident diabetes in meta-analysis of the four cohorts (P&amp;lt;0.001; range of odds ratios (OR) per 1-SD: 0.41-1.85). Among the strongest biomarkers were increased concentrations of branched-chained and aromatic amino acids (OR: 1.54-1.74) and triglycerides in very-low-density lipoproteins (VLDL; OR 1.78), and lower levels of omega-6 fatty acids (OR 0.61) and free cholesterol within large high-density lipoprotein (HDL; OR 0.41). A biomarker score was derived in three of the cohorts, comprised of phenylalanine, free cholesterol in large HDL, and the ratio of cholesterol esters to total lipids in large VLDL. When validated in the fourth cohort, those in the upper quartile of the biomarker score had considerably higher 15-year-risk for diabetes compared to those in the lowest quartile (OR 16.1). Interpretation: Metabolic aberrations across multiple molecular pathways are predictive of the long-term risk of type 2 diabetes in young adults. Comprehensive metabolic profiling may facilitate targeting preventive interventions at young asymptomatic individuals at increased risk for type 2 diabetes. Disclosure A.V. Ahola-Olli: None. L. Mustelin: Employee; Self; Nightingale Health Ltd. M. Kalimeri: Employee; Self; Nightingale Health Oy. J. Kettunen: Other Relationship; Self; Nightingale Ltd. J.J. Jokelainen: None. J. Auvinen: None. K.S. Puukka: None. A.S. Havulinna: None. T. Lehtimäki: None. M. Kähönen: None. V. Salomaa: Other Relationship; Self; Novo Nordisk Inc.. M. Perola: None. M. Jarvelin: None. M. Ala-Korpela: None. P. Wurtz: Employee; Self; Nightingale Health. Stock/Shareholder; Self; Nightingale Health.

Association of circulating metabolites with healthy diet and risk of cardiovascular disease: analysis of two cohort studies

Diet may modify metabolomic profiles towards higher or lower cardiovascular disease (CVD) risk. We aimed to identify metabolite profiles associated with high adherence to dietary recommendations - the Alternative Healthy Eating Index (AHEI) - and the extent to which metabolites associated with AHEI also predict incident CVD. Relations between AHEI score and 80 circulating lipids and metabolites, quantified by nuclear magnetic resonance metabolomics, were examined using linear regression models in the Whitehall II study (n = 4824, 55.9 ± 6.1 years, 28.0% women) and were replicated in the Cardiovascular Risk in Young Finns Study (n = 1716, 37.7 ± 5.0 years, 56.3% women). We used Cox models to study associations between metabolites and incident CVD over the 15.8-year follow-up in the Whitehall II study. After adjustment for confounders, higher AHEI score (indicating healthier diet) was associated with higher degree of unsaturation of fatty acids (FA) and higher ratios of polyunsaturated FA, omega-3 and docosahexaenoic acid relative to total FA in both Whitehall II and Young Finns studies. A concordance of associations of metabolites with higher AHEI score and lower CVD risk was observed in Whitehall II. Adherence to healthy diet seems to be associated with specific FA that reduce risk of CVD.

Comparison of the serum metabolic signatures based on 1H NMR between patients and a rat model of deep vein thrombosis

Deep vein thrombosis (DVT) and pulmonary embolism (PE) have high morbidity, reduce quality of life, and can cause death. Biomarkers or genetic risk factors have not been identified in patients with DVT. In present study, serum of 61 patients suffering from DVT and a rat DVT model (n = 10) were assayed by a proton nuclear magnetic resonance (1H NMR) metabolomics technique combing with multivariate statistical analysis to identify the metabolites. The MetPA platform was used to identify differences in the metabolic pathways between the rat model and patients. The metabolomics results discovered that 11 different metabolites in rats and 20 different metabolites in DVT patients. Seven metabolites both altered in the rats and patients. Moreover, we observed changes in the metabolic pathways, including carbohydrate metabolism, lipid metabolism, and amino acid metabolism that were induced immediately by the thrombosis. Pathway of aminoacyl-tRNA biosynthesis perturbed only in the patients which was associated with the genetic risk factor of DVT. The study demonstrated that serum 1H NMR metabolomics can be used to diagnose DVT in the clinic. The altered pathways related to thrombosis and genetics will provide a foundation and new strategies for understanding the pathological mechanism and pharmacological targets of DVT.

Current perspectives of nuclear magnetic resonance metabolomics in melanoma

Current perspectives of nuclear magnetic resonance metabolomics in melanoma

Assessing Exposome Effects on Pregnancy through Urine Metabolomics of a Portuguese (Estarreja) Cohort.

This nuclear magnetic resonance metabolomics study compared the influence of two different central Portugal exposomes, one of which comprised an important source of pollutants (the Estarreja Chemical Complex, ECC), on the urinary metabolic trajectory of a cohort of healthy pregnant women (total n = 107). An exposome-independent description of pregnancy metabolism was found to comprise a set of 18 metabolites reflecting expected changes in branched-chain amino acid catabolism and hormone and lipid metabolisms. In addition, a set of small changes in some metabolites was suggested to be exposome-dependent and characteristic of pregnant subjects from the Estarreja region. These results suggested that the Estarreja exposome may impact to a very low extent pregnancy metabolism, inducing slight changes in amino acid metabolism (alanine, glycine, and 3-hydroxyisobutyrate, possibly involved in valine metabolism), tricarboxylic acid (TCA) cycle (cis-aconitate), diet, or gut microflora (furoylglycine) as well as allantoin, 2-hydroxyisobutyrate, and an unassigned resonance at δ 8.45. Furthermore, the urine of Estarreja subjects was found to generally contain higher levels of 4-hydroxyphenylacetate and lower levels of citrate. However, out of the above metabolites, only glycine and citrate seemed to correlate with the proximity to the ECC, with slightly relative higher levels of these compounds found for subjects living closer to the ECC. This suggested possible small effects of local pollutants on energy metabolism, with the remaining exposome-dependent metabolite changes most probably originating from other aspects of the local exposome such as diet and lifestyle. Despite the limitation of this study regarding the unavailability of objective environmental parameters for the period under study, our results confirm the usefulness of metabolomics of human urine to gauge exposome effects on human health and, particularly, during pregnancy.

A novel NMR-based assay to measure circulating concentrations of branched-chain amino acids: Elevation in subjects with type 2 diabetes mellitus and association with carotid intima media thickness

ObjectivesPlasma branched-chain amino acid (BCAA) levels, measured on nuclear magnetic resonance (NMR) metabolomics research platforms or by mass spectrometry, have been shown to be associated with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). We developed a new test for quantification of BCAA on a clinical NMR analyzer and used this test to determine the clinical correlates of BCAA in 2 independent cohorts. Design and methodsThe performance of the NMR-based BCAA assay was evaluated. A method comparison study was performed with mass spectrometry (LC-MS/MS). Plasma BCAA were measured in the Insulin Resistance Atherosclerosis Study (IRAS, n = 1209; 376 T2DM subjects) and in a Groningen cohort (n = 123; 67 T2DM subjects). In addition, carotid intima media thickness (cIMT) was measured successfully in 119 subjects from the Groningen cohort. ResultsNMR-based BCAA assay results were linear over a range of concentrations. Coefficients of variation for inter- and intra-assay precision ranged from 1.8–6.0, 1.7–5.4, 4.4–9.1, and 8.8–21.3%, for total BCAA, valine, leucine, and isoleucine, respectively. BCAA quantified from the same samples using NMR and LC-MS/MS were highly correlated (R2 = 0.97, 0.95 and 0.90 for valine, leucine and isoleucine). In both cohorts total and individual BCAA were elevated in T2DM (P = 0.01 to ≤0.001). Moreover, cIMT was associated with BCAA independent of age, sex, T2DM and metabolic syndrome (MetS) categorization or alternatively of individual MetS components. ConclusionsBCAA levels, measured by NMR in the clinical laboratory, are elevated in T2DM and may be associated with cIMT, a proxy of subclinical atherosclerosis.

1H-nuclear magnetic resonance metabolomics revealing the intrinsic relationships between neurochemical alterations and neurobehavioral and neuropathological abnormalities in rats exposed to tris(2-chloroethyl)phosphate

Tris(2-chloroethyl)phosphate (TCEP) is a widely used environmental organic pollutant. Studies have revealed the presence of both TCEP and its metabolites in environmental media. The neurotoxicity of TCEP has been investigated in vitro but rarely in mammals. This study aimed to determine the neurotoxic effects of TCEP on rats and to explore the possible intrinsic relationships between neurochemical alterations and the neurotoxic effects. For this, 6-week-old female SD rats were administered 50, 100, or 250 mg/kg/d TCEP daily by oral gavage for 60 days. TCEP exposure produced neurotoxicity in the female SD rats. The Morris water maze results revealed a dose-dependent decline in spatial learning and memory functions of exposed rats. In addition, pathological examination of the brain showed apoptotic and necrotic lesions in the CA1 field pyramidal cells of the hippocampus; further, rats treated with the highest TCEP dose showed inflammatory cells and calcified/ossified foci in the cortex areas. Furthermore, 1H-nuclear magnetic resonance metabolomics results revealed that TCEP exposure interfered with normal biological processes, including amino acid and neurotransmitter metabolism, energy metabolism, and cell membrane function integrity by changing the concentrations of glutamate, γ-aminobutyric acid, N-acetyl-d-aspartate, creatine, and lactic acid metabolites in the brain of treated rats. However, the changes in the concentrations of taurine, myo-inositol, creatine, and choline metabolites, which are associated with antioxidant physiological processes, might be a neuroprotective mechanism to prevent the neurotoxicity induced by TCEP. Thus, metabolomics combined with neuropathology and neurobehavioral analyses provided critical insights to investigate the TCEP-induced neurotoxic effects and mechanisms.

Metabolic characterization of menopause: cross-sectional and longitudinal evidence

BackgroundWomen who experience menopause are at higher cardiometabolic risk and often display adverse changes in metabolic biomarkers compared with pre-menopausal women. It remains elusive whether the changes in cardiometabolic biomarkers during the menopausal transition are due to ovarian aging or chronological aging. Well-conducted longitudinal studies are required to determine this. The aim of this study was to explore the cross-sectional and longitudinal associations of reproductive status, defined according to the 2012 Stages of Reproductive Aging Workshop criteria, with 74 metabolic biomarkers, and establish whether any associations are independent of age-related changes.MethodsWe determined cross-sectional associations of reproductive status with metabolic profiling in 3,312 UK midlife women. In a subgroup of 1,492 women who had repeat assessments after 2.5 years, we assessed how the change in reproductive status was associated with the changes in metabolic biomarkers. Metabolic profiles were measured by high-throughput quantitative nuclear magnetic resonance metabolomics. In longitudinal analyses, we compared the change in metabolic biomarkers for each reproductive-status category change to that of the reference of being pre-menopausal at both time points. As all women aged by a similar amount during follow-up, these analyses contribute to distinguishing age-related changes from those related to change in reproductive status.ResultsConsistent cross-sectional and longitudinal associations of menopause with a wide range of metabolic biomarkers were observed, suggesting the transition to menopause induces multiple metabolic changes independent of chronological aging. The metabolic changes included increased concentrations of very small very low-density lipoproteins, intermediate-density lipoproteins, low-density lipoproteins (LDLs), remnant, and LDL cholesterol, and reduced LDL particle size, all toward an atherogenic lipoprotein profile. Increased inflammation was suggested via an inflammatory biomarker, glycoprotein acetyls, but not via C-reactive protein. Also, levels of glutamine and albumin increased during the transition. Most of these metabolic changes seen at the time of becoming post-menopausal remained or became slightly stronger during the post-menopausal years.ConclusionsThe transition to post-menopause has effects on multiple circulating metabolic biomarkers, over and above the underlying age trajectory. The adverse changes in multiple apolipoprotein-B-containing lipoprotein subclasses and increased inflammation may underlie women’s increased cardiometabolic risk in their post-menopausal years.

Effect of Dietary Counseling on a Comprehensive Metabolic Profile from Childhood to Adulthood

ObjectivesTo study the effects of repeated, infancy-onset dietary counseling on a detailed metabolic profile. Effects of dietary saturated fat replacement on circulating concentrations of metabolic biomarkers still remain unknown.Study designThe Special Turku Coronary Risk Factor Intervention Project (STRIP) study is a longitudinal, randomized atherosclerosis prevention trial in which repeated dietary counseling aimed at reducing the proportion of saturated fat intake. Nuclear magnetic resonance metabolomics quantified circulating metabolites from serum samples assessed at age 9 (n = 554), 11 (n = 553), 13 (n = 508), 15 (n = 517), 17 (n = 457), and 19 (n = 417) years.ResultsThe intervention reduced dietary intake of saturated fat (mean difference in daily percentage of total energy intake: −2.1 [95% CI −1.9 to −2.3]) and increased intake of polyunsaturated fat (0.6 [0.5-0.7]). The dietary counseling intervention led to greater serum proportions of polyunsaturated fatty acids (P < .001), with greater proportions of both circulating omega-3 (P = .02) and omega-6 (P < .001) fatty acids. The proportion of saturated fatty acids in serum was lower for both boys and girls in the intervention group (P < .001), whereas the serum proportion of monounsaturated fat was lower for boys in the intervention group only (P < .001). The intervention also reduced circulating intermediate-density lipoprotein and low-density lipoprotein lipid concentrations (P < .01). Dietary intervention effects on nonlipid biomarkers were minor except from greater concentrations of glutamine in the intervention group.ConclusionsRepeated dietary counseling from infancy to early adulthood yielded favorable effects on multiple circulating fatty acids and lipoprotein subclass lipids, particularly in boys. These molecular effects substantiate the beneficial role of saturated fat replacement on the metabolic risk profile.Trial registrationClinicalTrials.gov: NCT00223600.

Study on serum markers of prostate cancer by nuclear magnetic resonance-based metabolomics

Objective To investigate the clinical value of serum metabolomic profile of prostate cancer using nuclear magnetic resonance-based metabolomics. Methods The retrospective case control study was adopted.The clinical data of 31 patients with prostate cancer, 28 patients of prostatic hyperplasia and 31 healthy volunteers were enrolled in this study from May 2016 to May 2017 at the first affiliated hospital of Xinjiang medical university. In PCa group, the mean age was 66.3 years old, ranging 53-80 years old. In BPH group, the mean age was 59.3 years old, ranging 46-75 years old. In volunteer group, the mean age was 47.8 years old, ranging 35-62 years old.. The serum of the 3 groups was measured by 1H-NMR spectroscopy. Multivariate statistical analysis was used to analyze the serum differential metabolism of the 3 groups, including principal components analysis(PCA), partial least squares discriminant analysis(PLS-DA)and orthogonal partial least squares discriminant analysis(OPLS-DA). Results The multivariate statistical analysis of PCA that the rate of the first principal component 1(PC1) was 53.24%, the second principal component 2(PC2) was 25.31% and the cumulative contribution rate was 78.55%.Results of PLS-DA showed that partial data overlap of the three groups, but the separation trend was appeared.The variance of X(R2X) and Y(R2Y) matrixes and predictive value Q2 were 0.67, 0.60, and 0.42.The results of OPLS-DA showed that the difference among the PCa group and BPH group, healthy group were obvious. The separation trend were appeared and the differential metabolites could be screened effectively. The R2X、R2Y and Q2 was 0.24, 0.57, 0.21 and 0.30, 0.65, 0.36. 26 different serum metabolites were detected in the 3 groups, including citric acid, arginine, threonine, citrulline, glutamine, lactic acid, alanine, unsaturated fats, glycoprotein etc. Conclusions Compared with BPH group and healthy group, the serum of prostate cancer patients showed significant differences in metabolism. Nuclear magnetic resonance metabolomics analysis can effectively distinguish these serum metabolic differences. Key words: Prostate cancer; Nuclear magnetic resonance; Serum biomarkers; Metabolomics; Diagnosis

Serum Conjugated Linoleic Acid and Risk of Incident Heart Failure in Older Men: The British Regional Heart Study.

BackgroundEvidence largely from animal studies suggests that conjugated linoleic acid (CLA) may have cardiovascular health benefits. However, few prospective studies have examined the association between CLA and cardiovascular disease. We have prospectively examined the association between serum CLA and incident coronary heart disease and heart failure (HF) in older men.Methods and ResultsProspective study of 3806 men, aged 60 to 79 years, without prevalent HF followed up for an average of 13 years, during which there were 295 incident HF cases. A high‐throughput serum nuclear magnetic resonance metabolomics platform was used to measure CLA concentration in serum, expressed as a percentage of total fatty acids (CLA%). CLA% was adversely associated with cholesterol and high‐density lipoprotein cholesterol but was inversely associated with C‐reactive protein and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide; a marker of ventricular stress). No association was seen between CLA% and incident coronary heart disease. High CLA% was associated with significantly reduced risk of HF after adjustment for HF risk factors and C‐reactive protein (hazard ratio [95% confidence interval], 0.64 [0.43–0.96]; quartile 4 versus quartile 1). Elevated CLA% was associated with reduced HF risk only in those with higher dairy fat intake, a major dietary source of CLA (test for interaction P=0.03). The reduced risk of HF was partially explained by NT‐proBNP. High dairy fat intake was not associated with incident coronary heart disease but was associated with reduced risk of HF, largely because of the inverse effect of CLA.ConclusionsThe finding that high CLA% is associated with lower risk of incident HF in older men requires confirmation in larger studies.

Challenges in integrating component level technology and system level information from Ayurveda: Insights from NMR phytometabolomics and anti-HIV potential of select Ayurvedic medicinal plants

BackgroundInformation from Ayurveda meeting the analytical challenges of modern technology is an area of immense relevance. Apart from the cerebral task of bringing together two different viewpoints, the question at the pragmatic level remains ‘who benefits whom’. ObjectiveThe aim is to highlight the challenges in integration of information (Ayurvedic) and technology using test examples of Nuclear Magnetic Resonance (NMR) metabolomics and anti-HIV-1 potential of select Ayurvedic medicinal plants. The other value added objective is implications and relevance of such work for Ayurveda. Materials and methodsSix medicinal plants (Azadirachta indica, Tinospora cordifolia, Swertia chirata, Terminalia bellerica, Zingiber officinale and Symplocos racemosa) were studied using high resolution proton NMR spectroscopy based metabolomics and also evaluated for anti-HIV-1 activity on three pseudoviruses (ZM53 M.PB12, ZM109F.PB4, RHPA 4259.7). ResultsOf the six plants, T. bellerica and Z. officinale showed minimum cell cytotoxicity and maximum anti-HIV-1 potential. T. bellerica was effective against all the three HIV-1 pseudoviruses. Untargeted NMR profiling and multivariate analyses demonstrated that the six plants, all of which had different Ayurvedic pharmacological properties, showed maximum differences in the aromatic region of the spectra. ConclusionThe work adds onto the list of potential plants for anti-HIV-1 drug molecules. At the same time, it has drawn attention to the different perspectives of Ayurveda and Western medicine underscoring the inherent limitations of conceptual bilinguism between the two systems, especially in the context of medicinal plants. The study has also highlighted the potential of NMR metabolomics in study of plant extracts as used in Ayurveda.