Now showing 1 - 9 of 9
  • Publication
    Metabolomic-based identification of clusters that reflect dietary patterns
    Scope: Classification of subjects into dietary patterns generally relies on self-reporting dietary data which are prone to error. The aim of the present study was to develop a model for objective classification of people into dietary patterns based on metabolomic data. Methods and results: Dietary and urinary metabolomic data from the National Adult Nutrition Survey (NANS) was used in the analysis (n=567). Two-step cluster analysis was applied to the urinary data to identify clusters. The subsequent model was used in an independent cohort to classify people into dietary patterns. Two distinct dietary patterns were identified. Cluster 1 was characterized by significantly higher intakes of breakfast cereals, low fat and skimmed milks, potatoes, fruit and fish, fish dishes (P<0.05) representing a 'healthy' cluster. Cluster 2 had significantly higher intakes of chips/processed potatoes, meat products, savory snacks and high-energy beverages (P<0.05) representing an 'unhealthy cluster'. Classification was supported by significant differences in nutrient status (P<0.05). Validation in an independent group revealed that 94% of subjects were correctly classified. Conclusion: The model developed was capable of classifying individuals into dietary patterns based on metabolomics data. Future applications of this approach could be developed for rapid and objective assignment of subjects into dietary patterns.
      733Scopus© Citations 24
  • Publication
    Exploring the Links between Diet and Health in an Irish Cohort: A Lipidomic Approach
    Epidemiology and clinical studies provide clear evidence of the complex links between diet and health. To understand these links, reliable dietary assessment methods are pivotal. Biomarkers have emerged as more objective measures of intake compared with traditional dietary assessment methods. However, there are only a limited number of putative biomarkers of intake successfully identified and validated. The use of biomarkers that reflect food intake to examine diet related diseases represents the next step in biomarker research. Therefore, the aim of this study was to (1) identify and confirm biomarkers associated with dietary fat intake and (2) examine the relationship between those biomarkers with health parameters. Heatmap analysis identified a panel of 22 lipid biomarkers associated with total dietary fat intake in the Metabolic Challenge (MECHE) Study. Confirmation of four of these biomarkers demonstrated responsiveness to different levels of fat intake in a separate intervention study (NutriTech study). Linear regression identified a significant relationship between the panel of dietary fat biomarkers and HOMA-IR, with three lipid biomarkers (C16, PCaaC36:2, and PCae36:4) demonstrating significant associations. Identifying such links allows us to explore the relationship between diet and health to determine whether these biomarkers can be modulated through diet to improve health outcomes.
      811Scopus© Citations 7
  • Publication
    Demonstration of the utility of biomarkers for dietary intake assessment; proline betaine as an example
    Scope: There is a dearth of studies demonstrating the use of dietary biomarkers for determination of food intake. The objective of this study was to develop calibration curves for use in quantifying citrus intakes in an independent cohort. Methods and results: Participants (n=50) from the NutriTech food-intake study consumed standardized breakfasts for three consecutive days over three consecutive weeks. Orange juice intake decreased over the weeks. Urine samples were analyzed by NMR-spectroscopy and proline betaine was quantified and normalized to osmolality. Calibration curves were developed and used to predict citrus intake in an independent cohort; the Irish National Adult Nutrition Survey (NANS) (n=565). Proline betaine displayed a dose-response relationship to orange juice intake in 24h and fasting samples (p<0.001). In a test set, predicted orange juice intakes displayed excellent agreement with true intake. There were significant associations between predicted intake measured in 24h and fasting samples and true intake(r=0.710- 0.919). Citrus intakes predicted for the NANS cohort demonstrated good agreement with self-reported intake and this agreement improved following normalization to osmolality. Conclusion: The developed calibration curves successfully predicted citrus intakes in an independent cohort. Expansion of this approach to other foods will be important for the development of objective intake measurements.
    Scopus© Citations 59  901
  • Publication
    Sexual dimorphism, age, and fat mass are key phenotypic drivers of proteomic signatures
    Validated protein biomarkers are needed for assessing health trajectories, predicting and subclassifying disease, and optimizing diagnostic and therapeutic clinical decision-making. The sensitivity, specificity, accuracy, and precision of single or combinations of protein biomarkers may be altered by differences in physiological states limiting the ability to translate research results to clinically useful diagnostic tests. Aptamer based affinity assays were used to test whether low abundant serum proteins differed based on age, sex, and fat mass in a healthy population of 94 males and 102 females from the MECHE cohort. The findings were replicated in 217 healthy male and 377 healthy female participants in the DiOGenes consortium. Of the 1129 proteins in the panel, 141, 51, and 112 proteins (adjusted p < 0.1) were identified in the MECHE cohort and significantly replicated in DiOGenes for sexual dimorphism, age, and fat mass, respectively. Pathway analysis classified a subset of proteins from the 3 phenotypes to the complement and coagulation cascades pathways and to immune and coagulation processes. These results demonstrated that specific proteins were statistically associated with dichotomous (male vs female) and continuous phenotypes (age, fat mass), which may influence the identification and use of biomarkers of clinical utility for health diagnosis and therapeutic strategies.
      435Scopus© Citations 14
  • Publication
    Phenotypic factors influencing the variation in response of circulating cholesterol level to personalised dietary advice in the Food4me study
    Individual response to dietary interventions can be highly variable. The phenotypic characteristics of those who will respond positively to personalised dietary advice are largely unknown. The objective of this study was to compare the phenotypic profiles of differential responders to personalised dietary intervention, with a focus on total circulating cholesterol. Subjects from the Food4Me multi-centre study were classified as responders or non-responders to dietary advice based on the change in cholesterol level from baseline to month 6, with lower and upper quartiles defined as the responder and non-responder groups, respectively. There were no significant differences between the demographic and anthropometric profiles of the groups. Furthermore, with the exception of alcohol, there was no significant difference in reported dietary intake, at baseline. However, there were marked differences in baseline fatty acid profiles. The responder group had significantly higher levels of stearic acid (18:0, p=0.034) and lower levels of palmitic acid (16:0, p=0.009). Total monounsaturated fatty acids (p=0.016) and total polyunsaturated fatty acids (p=0.008) also differed between the groups. In a stepwise logistic regression model, age, baseline total cholesterol, glucose, five fatty acids and alcohol intake were selected as factors that successfully discriminated responders from non-responders, with sensitivity of 82% and specificity of 83%. The successful delivery of personalised dietary advice may depend on our ability to identify phenotypes that are responsive. The results demonstrate the potential use of metabolic profiles in identifying response to an intervention and could play an important role in the development of precision nutrition.  
      506Scopus© Citations 15
  • Publication
    Uncovering Factors Related to Pancreatic Beta-Cell Function
    Aim: The incidence of type 2 diabetes has increased rapidly on a global scale. Beta-cell dysfunction contributes to the overall pathogenesis of type 2 diabetes. However, factors contributing to beta-cell function are not clear. The aims of this study were (i) to identify factors related to pancreatic beta-cell function and (ii) to perform mechanistic studies in vitro. Methods: Three specific measures of beta-cell function were assessed for 110 participants who completed an oral glucose tolerance test as part of the Metabolic Challenge Study. Anthropometric and biochemical parameters were assessed as potential modulators of beta-cell function. Subsequent in vitro experiments were performed using the BRIN-BD11 pancreatic beta-cell line. Validation of findings were performed in a second human cohort. Results: Waist-to-hip ratio was the strongest anthropometric modulator of beta-cell function, with beta-coefficients of -0.33 (p = 0.001) and -0.30 (p = 0.002) for beta-cell function/homeostatic model assessment of insulin resistance (HOMA-IR), and disposition index respectively. Additionally, the resistin-to-adiponectin ratio (RA index) emerged as being strongly associated with beta-cell function, with beta-coefficients of -0.24 (p = 0.038) and -0.25 (p = 0.028) for beta-cell function/HOMA-IR, and disposition index respectively. Similar results were obtained using a third measure for beta-cell function. In vitro experiments revealed that the RA index was a potent regulator of acute insulin secretion where a high RA index (20ng ml-1 resistin, 5nmol l-1 g-adiponectin) significantly decreased insulin secretion whereas a low RA index (10ng ml-1 resistin, 10nmol l-1 g-adiponectin) significantly increased insulin secretion. The RA index was successfully validated in a second human cohort with beta-coefficients of -0.40 (p = 0.006) and -0.38 (p = 0.008) for beta-cell function/ HOMA-IR, and disposition index respectively. Conclusions: Waist-to-hip ratio and RA index were identified as significant modulators of beta-cell function. The ability of the RA index to modulate insulin secretion was confirmed in mechanistic studies. Future work should identify strategies to alter the RA index.
      426Scopus© Citations 4
  • Publication
    Capturing health and eating status through a Nutritional Perception Screening Questionnaire (NPSQ9) in a randomised internet-based Personalised Nutrition intervention: the Food4Me study
    Background: National guidelines emphasize healthy eating to promote wellbeing and prevention of non-communicable diseases. The perceived healthiness of food is determined by many factors affecting food intake. A positive perception of healthy eating has been shown to be associated with greater diet quality. Internet-based methodologies allow contact with large populations. Our present study aims to design and evaluate a short nutritional perception questionnaire, to be used as a screening tool for assessing nutritional status, and to predict an optimal level of personalisation in nutritional advice delivered via the Internet. Methods: Data from all participants who were screened and then enrolled into the Food4Me proof-of-principle study (n = 2369) were used to determine the optimal items for inclusion in a novel screening tool, the Nutritional Perception Screening Questionnaire-9 (NPSQ9). Exploratory and confirmatory factor analyses were performed on anthropometric and biochemical data and on dietary indices acquired from participants who had completed the Food4Me dietary intervention (n = 1153). Baseline and intervention data were analysed using linear regression and linear mixed regression, respectively. Results: A final model with 9 NPSQ items was validated against the dietary intervention data. NPSQ9 scores were inversely associated with BMI (β = −0.181, p < 0.001) and waist circumference (Β = −0.155, p < 0.001), and positively associated with total carotenoids (β = 0.198, p < 0.001), omega-3 fatty acid index (β = 0.155, p < 0.001), Healthy Eating Index (HEI) (β = 0.299, p < 0.001) and Mediterranean Diet Score (MDS) (β = 0. 279, p < 0.001). Findings from the longitudinal intervention study showed a greater reduction in BMI and improved dietary indices among participants with lower NPSQ9 scores. Conclusions: Healthy eating perceptions and dietary habits captured by the NPSQ9 score, based on nine questionnaire items, were associated with reduced body weight and improved diet quality. Likewise, participants with a lower score achieved greater health improvements than those with higher scores, in response to personalised advice, suggesting that NPSQ9 may be used for early evaluation of nutritional status and to tailor nutritional advice.
      703Scopus© Citations 11
  • Publication
    Within-person reproducibility and sensitivity to dietary change of C15:0 and C17:0 levels in dried blood spots: data from the European Food4Me Study
    ScopePrevious work highlighted the potential of odd-chain length saturated fatty acids as potential markers of dairy intake. The aim of this study was to assess the reproducibility of these biomarkers and their sensitivity to changes in dairy intake.Methods and ResultsFatty acid profiles and dietary intakes from food frequency questionnaires (FFQs) were measured three times over six months in the Food4Me Study. Reproducibility was explored through intra-class correlation coefficients (ICCs) and within-subject coefficients of variation (WCV). Sensitivity to changes in diet was examined using regression analysis. C15:0 blood levels showed high correlation over time (ICC: 0.62, 95% CI: 0.57, 0.68), however, the ICC for C17:0 was much lower (ICC: 0.32, 95% CI: 0.28, 0.46). The WCV for C15:0 was 16.6% and that for C17:0 was 14.6%. There were significant associations between changes in intakes of total dairy, high-fat dairy, cheese and butter and C15:0; and change in intakes of high-fat dairy and cream and C17:0.ConclusionsResults provide evidence of reproducibility of C15:0 levels over time and sensitivity to change in intake of high-fat dairy products with results comparable to the well-established biomarker of fish intake (EPA+DHA).
      423Scopus© Citations 13
  • Publication
    Estimation of chicken intake using metabolomics derived markers
    Background: Improved assessment of meat intake using metabolomics derived markers can provide objective data and could be helpful in clarifying proposed associations between meat intake and health.Objective: The objective was to identify novel markers of chicken intake using a metabolomics approach, and use markers to determine intake in an independent cohort. Methods: Ten participants (age, 62 y; BMI, 28.25 Kg/m2) in NutriTech Food Intake Study (NCT01684917) consumed increased amounts of chicken from 88 to 290 g/day over three weeks. Urine and blood samples were analyzed by NMR and MS, respectively. Multivariate data analysis was performed to identify markers associated with chicken intake. A calibration curve was built based on dose response association using NutriTech data. Bland and Altman analysis evaluated the agreement between reported and calculated chicken intake in National Adult Nutrition Survey (NANS) cohort. Results: Multivariate data analysis of postprandial and fasting urine samples collected in NutriTech revealed good discrimination between high (290 g/day) and low (88 g/day)  chicken intakes. Urinary metabolite profiles showed differences in metabolite levels between low and high chicken intakes. Examining metabolite profiles revealed guanidoacetate significantly increased from 1.47 to 3.66 mmol/L following increasing chicken intake from 88 to 290 g/day (P < 0.01). Using a calibration curve developed from NutriTech study, chicken intake was calculated in NANS, where chicken consumers had higher guanidoacetate excretion (0.70 mmol/L) than non-consumers (0.47 mmol/L) (P < 0.01). Bland and Altman analysis revealed good agreement between reported and calculated intakes with a bias of -30.2g/day. Plasma metabolite analysis demonstrated that 3-methylhistidine (3-Meth-His) was a more suitable indicator of chicken intake compared with 1-methylhistidine (1-Meth-His). Conclusions: Guanidoacetate was successfully identified and confirmed as a marker of chicken intake, and importantly its measurement in fasting urine samples could be used to determine chicken intake in a free-living population.
      566Scopus© Citations 23