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| 2. |
- Klåvus, Anton, et al.
(författare)
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“Notame”: Workflow for non-targeted LC-MS metabolic profiling
- 2020
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989 .- 2218-1989. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Metabolomics analysis generates vast arrays of data, necessitating comprehensive workflows involving expertise in analytics, biochemistry and bioinformatics in order to provide coherent and high-quality data that enable discovery of robust and biologically significant metabolic findings. In this protocol article, we introduce notame, an analytical workflow for non-targeted metabolic profiling approaches, utilizing liquid chromatography-mass spectrometry analysis. We provide an overview of lab protocols and statistical methods that we commonly practice for the analysis of nutritional metabolomics data. The paper is divided into three main sections: the first and second sections introducing the background and the study designs available for metabolomics research and the third section describing in detail the steps of the main methods and protocols used to produce, preprocess and statistically analyze metabolomics data and, finally, to identify and interpret the compounds that have emerged as interesting.
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| 3. |
- Kortesniemi, Maaria, et al.
(författare)
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Nutritional metabolomics: Recent developments and future needs
- 2023
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Ingår i: Current Opinion in Chemical Biology. - 1879-0402 .- 1367-5931. ; 77
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Forskningsöversikt (refereegranskat)abstract
- Metabolomics has rapidly been adopted as one of the key methods in nutrition research. This review focuses on the recent developments and updates in the field, including the analytical methodologies that encompass improved instrument sensitivity, sampling techniques and data integration (multiomics). Metabolomics has advanced the discovery and validation of dietary biomarkers and their implementation in health research. Metabolomics has come to play an important role in the understanding of the role of small molecules resulting from the diet–microbiota interactions when gut microbiota research has shifted towards improving the understanding of the activity and functionality of gut microbiota rather than composition alone. Currently, metabolomics plays an emerging role in precision nutrition and the recent developments therein are discussed.
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| 4. |
- Landberg, Rikard, 1981, et al.
(författare)
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Dietary biomarkers-an update on their validity and applicability in epidemiological studies
- 2023
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Ingår i: Nutrition Reviews. - 0029-6643 .- 1753-4887. ; In Press
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Forskningsöversikt (refereegranskat)abstract
- The aim of this literature review was to identify and provide a summary update on the validity and applicability of the most promising dietary biomarkers reflecting the intake of important foods in the Western diet for application in epidemiological studies. Many dietary biomarker candidates, reflecting intake of common foods and their specific constituents, have been discovered from intervention and observational studies in humans, but few have been validated. The literature search was targeted for biomarker candidates previously reported to reflect intakes of specific food groups or components that are of major importance in health and disease. Their validity was evaluated according to 8 predefined validation criteria and adapted to epidemiological studies; we summarized the findings and listed the most promising food intake biomarkers based on the evaluation. Biomarker candidates for alcohol, cereals, coffee, dairy, fats and oils, fruits, legumes, meat, seafood, sugar, tea, and vegetables were identified. Top candidates for all categories are specific to certain foods, have defined parent compounds, and their concentrations are unaffected by nonfood determinants. The correlations of candidate dietary biomarkers with habitual food intake were moderate to strong and their reproducibility over time ranged from low to high. For many biomarker candidates, critical information regarding dose response, correlation with habitual food intake, and reproducibility over time is yet unknown. The nutritional epidemiology field will benefit from the development of novel methods to combine single biomarkers to generate biomarker panels in combination with self-reported data. The most promising dietary biomarker candidates that reflect commonly consumed foods and food components for application in epidemiological studies were identified, and research required for their full validation was summarized.
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| 5. |
- Noerman, Stefania, 1987, et al.
(författare)
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Associations of the serum metabolite profile with a healthy Nordic diet and risk of coronary artery disease
- 2021
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 1532-1983 .- 0261-5614. ; 40:5, s. 3250-3262
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Tidskriftsartikel (refereegranskat)abstract
- Background & aim: A healthy Nordic diet (HND) rich in wholegrain cereals, berries, vegetables, and fish, has been associated with a lower risk of cardiovascular disease, but the molecular links remain unclear. Here, we present the application of nontargeted metabolic profiling based on liquid chromatography with tandem mass spectrometry (LC-MS/MS) to identify metabolites that would potentially reflect the adherence to HND and their relationship with the risk of coronary artery disease (CAD). Methods: From a Finnish population-based prospective cohort (Kuopio Ischaemic Heart Disease Risk Factor Study; KIHD), we collected 364 baseline serum samples in 4 groups: 1) 94 participants with high adherence to HND who developed CAD during the follow-up of 20.4 ± 7.6 years (cases), 2) 88 participants with high adherence who did not develop CAD during follow-up (controls), 3) 93 CAD cases with low adherence, and 4) 89 controls with low adherence. Results: Indolepropionic acid, proline betaine, vitamin E derivatives, and medium-chain acylcarnitines were associated with adherence to HND after adjustments for age, waist-to-hip ratio (WHR), physical activity, and total cholesterol. These metabolites also correlated negatively with blood lipid profiles, BMI, insulin, inflammation marker high-sensitivity C reactive protein (hsCRP), smoking, and alcohol consumption, as well as positively with physical activity. Predictors of CAD risk included several lipid molecules, which also indicated lower adherence to HND. But, only the associations with the plasmalogens PC(O-16:0/18:2) and PC(O-16:1/18:2) remained significant after adjusting for age, smoking, systolic blood pressure, LDL cholesterol, and WHR. These plasmalogens did not correlate with any investigated risk factors of CAD at baseline, which may highlight their potential as novel predictors of CAD risk. Interestingly, the metabolic profile predicting CAD risk differed based on the adherence to HND. Also, HND adherence was more distinct within CAD cases than controls, which may emphasize the interaction between HND adherence and CAD risk. Conclusions: The association between higher adherence to HND and a lower risk of CAD likely involves a complex interaction of various endogenous, plant-, and microbial-derived metabolites.
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| 6. |
- Noerman, Stefania, 1987, et al.
(författare)
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Blood metabolite profiles linking dietary patterns with health—Toward precision nutrition
- 2023
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 293:4, s. 408-432
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Forskningsöversikt (refereegranskat)abstract
- Diet is one of the most important exposures that may affect health throughout life span. Investigations on dietary patterns rather than single food components are gaining in popularity because they take the complexity of the whole dietary context into account. Adherence to such dietary patterns can be measured by using metabolomics, which allows measurements of thousands of molecules simultaneously. Derived metabolite signatures of dietary patterns may reflect the consumption of specific groups of foods or their constituents originating from the dietary pattern per se, or the physiological response toward the food-derived metabolites, their interaction with endogenous metabolism, and exogenous factors such as gut microbiota. Here, we review and discuss blood metabolite fingerprints of healthy dietary patterns. The plasma concentration of several food-derived metabolites—such as betaines from whole grains and n − 3 polyunsaturated fatty acids and furan fatty acids from fish—seems to consistently reflect the intake of common foods of several healthy dietary patterns. The metabolites reflecting shared features of different healthy food indices form biomarker panels for which specific, targeted assays could be developed. The specificity of such biomarker panels would need to be validated, and proof-of-concept feeding trials are needed to evaluate to what extent the panels may mediate the effects of dietary patterns on disease risk indicators or if they are merely food intake biomarkers. Metabolites mediating health effects may represent novel targets for precision prevention strategies of clinical relevance to be verified in future studies.
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| 7. |
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| 8. |
- Noerman, Stefania, et al.
(författare)
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Fasting plasma metabolites reflecting meat consumption and their associations with incident type 2 diabetes in two Swedish cohorts
- 2024
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier. - 0002-9165 .- 1938-3207.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Consumption of processed red meat has been associated with increased risk of developing type 2 diabetes (T2D), but challenges in dietary assessment call for objective intake biomarkers.Objectives: This study aimed to investigate metabolite biomarkers of meat intake and their associations with T2D risk. Methods: Fasting plasma samples were collected from a case–control study nested within Västerbotten Intervention Program (VIP) (214 females and 189 males) who developed T2D after a median follow-up of 7 years. Panels of biomarker candidates reflecting the consumption of total, processed, and unprocessed red meat and poultry were selected from the untargeted metabolomics data collected on the controls. Observed associations were then replicated in Swedish Mammography clinical subcohort in Uppsala (SMCC) (n = 4457 females). Replicated metabolites were assessed for potential association with T2D risk using multivariable conditional logistic regression in the discovery and Cox regression in the replication cohorts.Results: In total, 15 metabolites were associated with ≥1 meat group in both cohorts. Acylcarnitines 8:1, 8:2, 10:3, reflecting higher processed meat intake [r > 0.22, false discovery rate (FDR) < 0.001 for VIP and r > 0.05; FDR < 0.001 for SMCC) were consistently associated with higher T2D risk in both data sets. Conversely, lysophosphatidylcholine 17:1 and phosphatidylcholine (PC) 15:0/18:2 were associated with lower processed meat intake (r < −0.12; FDR < 0.023, for VIP and r < −0.05; FDR < 0.001, for SMCC) and with lower T2D risk in both data sets, except for PC 15:0/18:2, which was significant only in the VIP cohort. All associations were attenuated after adjustment for BMI (kg/m2).Conclusions: Consistent associations of biomarker candidates involved in lipid metabolism between higher processed red meat intake with higher T2D risk and between those reflecting lower intake with the lower risk may suggest a relationship between processed meat intake and higher T2D risk. However, attenuated associations after adjusting for BMI indicates that such a relationship may at least partly be mediated or confounded by BMI.
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| 9. |
- Noerman, Stefania, 1987, et al.
(författare)
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Fasting plasma metabolites reflecting meat consumption and their associations with incident type 2 diabetes in two Swedish cohorts
- 2024
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Ingår i: The American journal of clinical nutrition. - : Elsevier. - 0002-9165 .- 1938-3207. ; 119:5, s. 1280-1292
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Tidskriftsartikel (refereegranskat)abstract
- Background: Consumption of processed red meat has been associated with increased risk of developing type 2 diabetes (T2D), but challenges in dietary assessment call for objective intake biomarkers. Objectives: This study aimed to investigate metabolite biomarkers of meat intake and their associations with T2D risk. Methods: Fasting plasma samples were collected from a case–control study nested within Västerbotten Intervention Program (VIP) (214 females and 189 males) who developed T2D after a median follow-up of 7 years. Panels of biomarker candidates reflecting the consumption of total, processed, and unprocessed red meat and poultry were selected from the untargeted metabolomics data collected on the controls. Observed associations were then replicated in Swedish Mammography clinical subcohort in Uppsala (SMCC) (n = 4457 females). Replicated metabolites were assessed for potential association with T2D risk using multivariable conditional logistic regression in the discovery and Cox regression in the replication cohorts. Results: In total, 15 metabolites were associated with ≥1 meat group in both cohorts. Acylcarnitines 8:1, 8:2, 10:3, reflecting higher processed meat intake [r > 0.22, false discovery rate (FDR) < 0.001 for VIP and r > 0.05; FDR < 0.001 for SMCC) were consistently associated with higher T2D risk in both data sets. Conversely, lysophosphatidylcholine 17:1 and phosphatidylcholine (PC) 15:0/18:2 were associated with lower processed meat intake (r < −0.12; FDR < 0.023, for VIP and r < −0.05; FDR < 0.001, for SMCC) and with lower T2D risk in both data sets, except for PC 15:0/18:2, which was significant only in the VIP cohort. All associations were attenuated after adjustment for BMI (kg/m2). Conclusions: Consistent associations of biomarker candidates involved in lipid metabolism between higher processed red meat intake with higher T2D risk and between those reflecting lower intake with the lower risk may suggest a relationship between processed meat intake and higher T2D risk. However, attenuated associations after adjusting for BMI indicates that such a relationship may at least partly be mediated or confounded by BMI.
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| 10. |
- Noerman, Stefania, 1987, et al.
(författare)
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Serum metabolites associated with wholegrain consumption using nontargeted metabolic profiling: a discovery and reproducibility study
- 2023
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 62:2, s. 713-726
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To identify fasting serum metabolites associated with WG intake in a free-living population adjusted for potential confounders. Methods: We selected fasting serum samples at baseline from a subset (n = 364) of the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) cohort. The samples were analyzed using nontargeted metabolomics with liquid chromatography coupled with mass spectrometry (LC–MS). Association with WG intake was investigated using both random forest followed by linear regression adjusted for age, BMI, smoking, physical activity, energy and alcohol consumption, and partial Spearman correlation adjusted for the same covariates. Features selected by any of these models were shortlisted for annotation. We then checked if we could replicate the findings in an independent subset from the same cohort (n = 200). Results: Direct associations were observed between WG intake and pipecolic acid betaine, tetradecanedioic acid, four glucuronidated alkylresorcinols (ARs), and an unknown metabolite both in discovery and replication cohorts. The associations remained significant (FDR<0.05) even after adjustment for the confounders in both cohorts. Sinapyl alcohol was positively correlated with WG intake in both cohorts after adjustment for the confounders but not in linear models in the replication cohort. Some microbial metabolites, such as indolepropionic acid, were positively correlated with WG intake in the discovery cohort, but the correlations were not replicated in the replication cohort. Conclusions: The identified associations between WG intake and the seven metabolites after adjusting for confounders in both discovery and replication cohorts suggest the potential of these metabolites as robust biomarkers of WG consumption.
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