| 1. |
- Ahmed, Hany, et al.
(författare)
-
Microbiota-derived metabolites as drivers of gut–brain communication
- 2022
-
Ingår i: Gut Microbes. - : Informa UK Limited. - 1949-0984 .- 1949-0976. ; 14:1
-
Forskningsöversikt (refereegranskat)abstract
- Alterations in the gut microbiota composition have been associated with a range of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. The gut microbes transform and metabolize dietary- and host-derived molecules generating a diverse group of metabolites with local and systemic effects. The bi-directional communication between brain and the microbes residing in the gut, the so-called gut–brain axis, consists of a network of immunological, neuronal, and endocrine signaling pathways. Although the full variety of mechanisms of the gut–brain crosstalk is yet to be established, the existing data demonstrates that a single metabolite or its derivatives are likely among the key inductors within the gut–brain axis communication. However, more research is needed to understand the molecular mechanisms underlying how gut microbiota associated metabolites alter brain functions, and to examine if different interventional approaches targeting the gut microbiota could be used in prevention and treatment of neurological disorders, as reviewed herein. Abbreviations:4-EPS 4-ethylphenylsulfate; 5-AVA(B) 5-aminovaleric acid (betaine); Aβ Amyloid beta protein; AhR Aryl hydrocarbon receptor; ASD Autism spectrum disorder; BBB Blood–brain barrier; BDNF Brain-derived neurotrophic factor; CNS Central nervous system; GABA ɣ-aminobutyric acid; GF Germ-free; MIA Maternal immune activation; SCFA Short-chain fatty acid; 3M-4-TMAB 3-methyl-4-(trimethylammonio)butanoate; 4-TMAP 4-(trimethylammonio)pentanoate; TMA(O) Trimethylamine(-N-oxide); TUDCA Tauroursodeoxycholic acid; ZO Zonula occludens proteins.
|
|
| 2. |
- Haikonen, Retu, et al.
(författare)
-
Diet- and microbiota-related metabolite, 5-aminovaleric acid betaine (5-AVAB), in health and disease
- 2022
-
Ingår i: Trends in Endocrinology and Metabolism. - : Elsevier BV. - 1879-3061 .- 1043-2760. ; 33:7, s. 463-480
-
Forskningsöversikt (refereegranskat)abstract
- 5-Aminovaleric acid betaine (5-AVAB) is a trimethylated compound associated with the gut microbiota, potentially produced endogenously, and related to the dietary intake of certain foods such as whole grains. 5-AVAB accumulates within the metabolically active tissues and has been typically found in higher concentrations in the heart, muscle, and brown adipose tissue. Furthermore, 5-AVAB has been associated with positive health effects such as fetal brain development, insulin secretion, and reduced cancer risk. However, it also has been linked with some negative health outcomes such as cardiovascular disease and fatty liver disease. At the cellular level, 5-AVAB can influence cellular energy metabolism by reducing β-oxidation of fatty acids. This review will focus on the metabolic role of 5-AVAB with respect to both physiology and pathology. Moreover, the analytics and origin of 5-AVAB and related compounds will be reviewed.
|
|
| 3. |
- Hanhineva, Kati, 1972
(författare)
-
Application of Metabolomics for the Assessment of Health Effects of Whole grain Foods
- 2021
-
Ingår i: Whole Grains and Health: Second Edition. - : Wiley. ; , s. 375-388
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Metabolomics techniques offer the possibility to semi-quantitatively examine a wide scale of endogenous metabolites potentially affected by the consumption of whole grain. Various metabolite analysis applications, including both mass spectrometry and NMR-based technology, have been utilized in this research field. This chapter focuses on the published metabolomics research regarding endogenous metabolic changes observed in studies involving whole grain consumption and impact on health. The evidence from prospective, observational studies on the impact of whole grains on human health is convincing as high consumption has been associated with reduced risk of major chronic diseases including cardiovascular diseases. Very few metabolomics approaches have been undertaken on epidemiological studies involving examination of dietary intake of whole grain products. While plasma and urine are the predominant sample materials available from human studies, animal trials are often necessitated in order to find out more detailed information on the perturbations caused by the dietary differences on cellular metabolism.
|
|
| 4. |
- Klåvus, Anton, et al.
(författare)
-
“Notame”: Workflow for non-targeted LC-MS metabolic profiling
- 2020
-
Ingår i: Metabolites. - : MDPI AG. - 2218-1989 .- 2218-1989. ; 10:4
-
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.
|
|
| 5. |
- Koistinen, Ville Mikael, et al.
(författare)
-
Metabolic changes in response to varying whole-grain wheat and rye intake
- 2024
-
Ingår i: npj Science of Food. - 2396-8370. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Epidemiological studies have shown associations between whole-grain intake and lowered disease risk. A sufficient level of whole-grain intake to reach the health benefits has not been established, and there is limited knowledge about the impact of whole-grain intake on metabolite levels. In this clinical intervention study, we aimed to identify plasma and urine metabolites associated with two different intake levels of whole-grain wheat and rye and to correlate them with clinical plasma biomarkers. Healthy volunteers (N = 68) were divided into two groups receiving either whole-grain wheat or whole-grain rye in two four-week interventions with 48 and 96 g/d of whole grains consumed. The metabolomics of the plasma samples was performed with UPLC–QTOF-MS. Plasma alkylresorcinols were quantified with GC-MS and plasma and urinary mammalian lignans with HPLC-ECD. The high-dose intervention impacted the metabolite profile, including microbial metabolites, more in the rye-enriched diet compared with wheat. Among the increased metabolites were alkylresorcinol glucuronides, sinapyl alcohol, and pipecolic acid betaine, while the decreased metabolites included acylcarnitines and ether lipids. Plasma alkylresorcinols, urinary enterolactone, and total mammalian lignans reflected the study diets in a dose-dependent manner. Several key metabolites linked with whole-grain consumption and gut microbial metabolism increased in a linear manner between the two interventions. The results reveal that an increase in whole-grain intake, particularly rye, is strongly reflected in the metabolite profile, is correlated with clinical variables, and suggests that a diet rich in whole grains promotes the growth and/or metabolism of microbes producing potentially beneficial microbial metabolites.
|
|
| 6. |
- Koistinen, Ville M., et al.
(författare)
-
Metabolite pattern derived from Lactiplantibacillus plantarum : fermented rye foods and in vitro gut fermentation synergistically inhibits bacterial growth
- 2022
-
Ingår i: Molecular Nutrition & Food Research. - : John Wiley & Sons. - 1613-4125 .- 1613-4133. ; 66:21
-
Tidskriftsartikel (refereegranskat)abstract
- Scope: Fermentation improves many food characteristics using microbes, such as lactic acid bacteria (LAB). Recent studies suggest fermentation may also enhance the health properties, but mechanistic evidence is lacking. We aimed to identify a metabolite pattern reproducibly produced during sourdough and in vitro colonic fermentation of various whole-grain rye products and how it affects the growth of bacterial species of potential importance to health and disease.Methods and results: We used Lactiplantibacillus plantarum DSMZ 13890 strain, previously shown to favour rye as its substrate. Using LC-MS metabolomics, we found seven microbial metabolites commonly produced during the fermentations, including dihydroferulic acid, dihydrocaffeic acid, and five amino acid metabolites, and stronger inhibition was achieved when exposing the bacteria to a mixture of the metabolites in vitro compared to individual compound exposures.Conclusion: Our study suggests that metabolites produced by LAB may synergistically modulate the local microbial ecology, such as in the gut. This could provide new hypotheses on how fermented foods influence human health via diet–microbiota interactions.
|
|
| 7. |
- Koistinen, Ville Mikael, et al.
(författare)
-
Side-stream products of malting: a neglected source of phytochemicals
- 2020
-
Ingår i: npj Science of Food. - : Springer Science and Business Media LLC. - 2396-8370. ; 4:1
-
Tidskriftsartikel (refereegranskat)abstract
- Whole grain consumption reduces the risk of several chronic diseases. A major contributor to the effect is the synergistic and additive effect of phytochemicals. Malting is an important technological method to process whole grains; the main product, malted grain, is used mainly for brewing, but the process also yields high amounts of side-stream products, such as rootlet. In this study, we comprehensively determined the phytochemical profile of barley, oats, rye, and wheat in different stages of malting and the subsequent extraction phases to assess the potential of malted products and side-streams as a dietary source of bioactive compounds. Utilizing semi-quantitative LC–MS metabolomics, we annotated 285 phytochemicals from the samples, belonging to more than 13 chemical classes. Malting significantly altered the levels of the compounds, many of which were highly increased in the rootlet. Whole grain cereals and the malting products were found to be a diverse and rich source of phytochemicals, highlighting the value of these whole foods as a staple. The characterization of phytochemicals from the 24 different sample types revealed previously unknown existence of some of the compound classes in certain species. The rootlet deserves more attention in human nutrition, rather than its current use mainly as feed, to benefit from its high content of bioactive components.
|
|
| 8. |
- Landberg, Rikard, 1981, et al.
(författare)
-
Biomarkers of a healthy nordic diet : from dietary exposure biomarkers to microbiota signatures in the metabolome
- 2020
-
Ingår i: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 12:1
-
Forskningsöversikt (refereegranskat)abstract
- Whole diets and dietary patterns are increasingly highlighted in modern nutrition and health research instead of single food items or nutrients alone. The Healthy Nordic Diet is a dietary pattern typically associated with beneficial health outcomes in observational studies, but results from randomized controlled trials are mixed. Dietary assessment is one of the greatest challenges in observational studies and compliance is a major challenge in dietary interventions. During the last decade, research has shown the great importance of the gut microbiota in health and disease. Studies have have both shown that the Nordic diet affects the gut microbiota and that the gut microbiota predicts the effects of such a diet. Rapid technique developments in the area of high-throughput mass spectrometry have enabled the large-scale use of metabolomics both as an objective measurement of dietary intake as well as in providing the final readout of the endogenous metabolic processes and the impact of the gut microbiota. In this review, we give an update on the current status on biomarkers that reflect a Healthy Nordic Diet or individual components thereof (food intake biomarkers), biomarkers that show the effects of a Healthy Nordic Diet and biomarkers reflecting the role of a Healthy Nordic Diet on the gut microbiota as well as how the gut microbiota or derived molecules may be used to predict the effects of a Healthy Nordic Diet on different outcomes.
|
|
| 9. |
- Leung, Howell, et al.
(författare)
-
Risk assessment with gut microbiome and metabolite markers in NAFLD development
- 2022
-
Ingår i: Science Translational Medicine. - : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 14:648, s. eabk0855-
-
Tidskriftsartikel (refereegranskat)abstract
- A growing body of evidence suggests interplay between the gut microbiota and the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the role of the gut microbiome in early detection of NAFLD is unclear. Prospective studies are necessary for identifying reliable, microbiome markers for early NAFLD. We evaluated 2487 individuals in a community-based cohort who were followed up 4.6 years after initial clinical examination and biospecimen sampling. Metagenomic and metabolomic characterizations using stool and serum samples taken at baseline were performed for 90 participants who progressed to NAFLD and 90 controls who remained NAFLD free at the follow-up visit. Cases and controls were matched for gender, age, body mass index (BMI) at baseline and follow-up, and 4-year BMI change. Machine learning models integrating baseline microbial signatures (14 features) correctly classified participants (auROCs of 0.72 to 0.80) based on their NAFLD status and liver fat accumulation at the 4-year follow up, outperforming other prognostic clinical models (auROCs of 0.58 to 0.60). We confirmed the biological relevance of the microbiome features by testing their diagnostic ability in four external NAFLD case-control cohorts examined by biopsy or magnetic resonance spectroscopy, from Asia, Europe, and the United States. Our findings raise the possibility of using gut microbiota for early clinical warning of NAFLD development.
|
|
| 10. |
- Low, Dorrain Yanwen, et al.
(författare)
-
Data sharing in PredRet for accurate prediction of retention time: Application to plant food bioactive compounds
- 2021
-
Ingår i: Food Chemistry. - : Elsevier BV. - 0308-8146 .- 1873-7072. ; 357
-
Tidskriftsartikel (refereegranskat)abstract
- Prediction of retention times (RTs) is increasingly considered in untargeted metabolomics to complement MS/MS matching for annotation of unidentified peaks. We tested the performance of PredRet (http://predret.org/) to predict RTs for plant food bioactive metabolites in a data sharing initiative containing entry sets of 29–103 compounds (totalling 467 compounds, >30 families) across 24 chromatographic systems (CSs). Between 27 and 667 predictions were obtained with a median prediction error of 0.03–0.76 min and interval width of 0.33–8.78 min. An external validation test of eight CSs showed high prediction accuracy. RT prediction was dependent on shape and type of LC gradient, and number of commonly measured compounds. Our study highlights PredRet's accuracy and ability to transpose RT data acquired from one CS to another CS. We recommend extensive RT data sharing in PredRet by the community interested in plant food bioactive metabolites to achieve a powerful community-driven open-access tool for metabolomics annotation.
|
|
| 11. |
- Meuronen, Topi, et al.
(författare)
-
FADS1 rs174550 genotype and high linoleic acid diet modify plasma PUFA phospholipids in a dietary intervention study
- 2022
-
Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 61:2, s. 1109-1120
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Fatty acid desaturase 1 (FADS1) gene encodes for delta-5 desaturase enzyme which is needed in conversion of linoleic acid (LA) to arachidonic acid (AA). Recent studies have shown that response to dietary PUFAs differs between the genotypes in circulating fatty acids. However, interactions between the FADS1 genotype and dietary LA on overall metabolism have not been studied. Objectives: We aimed to examine the interactions of FADS1 rs174550 genotypes (TT and CC) and high-LA diet to identify plasma metabolites that respond differentially to dietary LA according to the FADS1 genotype. Methods: A total of 59 men (TT n = 26, CC n = 33) consumed a sunflower oil supplemented diet for 4 weeks. Daily dose of 30, 40, or 50 ml was calculated based on body mass index. It resulted in 17–28 g of LA on top of the usual daily intake. Fasting plasma samples at the beginning and at the end of the intervention were analyzed with LC–MS/MS non-targeted metabolomics method. Results: At the baseline, the carriers of FADS1 rs174550-TT genotype had higher abundance of long-chain PUFA phospholipids compared to the FADS1 rs174550-CC one. In response to the high-LA diet, LA phospholipids and long-chain acylcarnitines increased and lysophospholipids decreased in fasting plasma similarly in both genotypes. LysoPE (20:4), LysoPC (20:4), and PC (16:0_20:4) decreased and cortisol increased in the carriers of rs174550-CC genotype; however, these genotype–diet interactions were not significant after correction for multiple testing. Conclusion: Our findings show that both FADS1 rs174550 genotype and high-LA diet modify plasma phospholipid composition. Trial registration: The study was registered to ClinicalTrials: NCT02543216, September 7, 2015 (retrospectively registered).
|
|
| 12. |
- Noerman, Stefania, 1987, et al.
(författare)
-
Associations of the serum metabolite profile with a healthy Nordic diet and risk of coronary artery disease
- 2021
-
Ingår i: Clinical Nutrition. - : Elsevier BV. - 1532-1983 .- 0261-5614. ; 40:5, s. 3250-3262
-
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.
|
|
| 13. |
- Noerman, Stefania, 1987, et al.
(författare)
-
Serum metabolites associated with wholegrain consumption using nontargeted metabolic profiling: a discovery and reproducibility study
- 2023
-
Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 62:2, s. 713-726
-
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.
|
|
| 14. |
- Nordin, Elise, 1985, et al.
(författare)
-
An inverse association between plasma benzoxazinoid metabolites and PSA after rye intake in men with prostate cancer revealed with a new method
- 2022
-
Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer (PC) is a common cancer among men, and preventive strategies are warranted. Benzoxazinoids (BXs) in rye have shown potential against PC in vitro but human studies are lacking. The aim was to establish a quantitative method for analysis of BXs and investigate their plasma levels after a whole grain/bran rye vs refined wheat intervention, as well as exploring their association with PSA, in men with PC. A quantitative method for analysis of 22 BXs, including novel metabolites identified by mass spectrometry and NMR, was established, and applied to plasma samples from a randomized crossover study where patients with indolent PC (n = 17) consumed 485 g whole grain rye/rye bran or fiber supplemented refined wheat daily for 6 wk. Most BXs were significantly higher in plasma after rye (0.3–19.4 nmol/L in plasma) vs. refined wheat (0.05–2.9 nmol/L) intake. HBOA-glc, 2-HHPAA, HBOA-glcA, 2-HPAA-glcA were inversely correlated to PSA in plasma (p < 0.04). To conclude, BXs in plasma, including metabolites not previously analyzed, were quantified. BX metabolites were significantly higher after rye vs refined wheat consumption. Four BX-related metabolites were inversely associated with PSA, which merits further investigation.
|
|
| 15. |
- Poutanen, Kaisa S., et al.
(författare)
-
Grains - a major source of sustainable protein for health
- 2022
-
Ingår i: Nutrition Reviews. - : Oxford University Press (OUP). - 0029-6643 .- 1753-4887. ; 80:6, s. 1648-1663
-
Forskningsöversikt (refereegranskat)abstract
- Cereal grains are the main dietary source of energy, carbohydrates, and plant proteins world-wide. Currently, only 41% of grains are used for human consumption, and up to 35% are used for animal feed. Cereals have been overlooked as a source of environmentally sustainable and healthy plant proteins and could play a major role in transitioning towards a more sustainable food system for healthy diets. Cereal plant proteins are of good nutritional quality, but lysine is often the limiting amino acid. When consumed as whole grains, cereals provide health-protecting components such as dietary fiber and phytochemicals. Shifting grain use from feed to traditional foods and conceptually new foods and ingredients could improve protein security and alleviate climate change. Rapid development of new grain-based food ingredients and use of grains in new food contexts, such as dairy replacements and meat analogues, could accelerate the transition. This review discusses recent developments and outlines future perspectives for cereal grain use.
|
|
| 16. |
- Schillemans, Tessa, et al.
(författare)
-
Associations of PFAS-related plasma metabolites with cholesterol and triglyceride concentrations
- 2023
-
Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 216
-
Tidskriftsartikel (refereegranskat)abstract
- The wide-spread environmental pollutants per- and polyfluoroalkyl substances (PFAS) have repeatedly been associated with elevated serum cholesterol in humans. However, underlying mechanisms are still unclear. Furthermore, we have previously observed inverse associations with plasma triglycerides. To better understand PFAS-induced effects on lipid pathways we investigated associations of PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations. We used 290 PFAS-related metabolite features that we previously discovered from untargeted liquid chromatography-mass spectometry metabolomics in a case-control study within the Swedish Västerbotten Intervention Programme cohort. Herein, we studied associations of these PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations in plasma samples from 187 healthy control subjects collected on two occasions between 1991 and 2013. The PFAS-related features did not associate with cholesterol, but 50 features were associated with triglycerides. Principal component analysis on these features indicated that one metabolite pattern, dominated by glycerophospholipids, correlated with longer chain PFAS and associated inversely with triglycerides (both cross-sectionally and prospectively), after adjustment for confounders. The observed time-trend of the metabolite pattern resembled that of the longer chain PFAS, with higher levels during the years 2004–2010. Mechanisms linking PFAS exposures to triglycerides may thus occur via longer chain PFAS affecting glycerophospholipid metabolism. If the results reflect a cause-effect association, as implied by the time-trend and prospective analyses, this may affect the general adult population.
|
|
| 17. |
- Schillemans, Tessa, et al.
(författare)
-
Plasma metabolites associated with exposure to perfluoroalkyl substances and risk of type 2 diabetes – A nested case-control study
- 2021
-
Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 146
-
Tidskriftsartikel (refereegranskat)abstract
- Perfluoroalkyl substances (PFAS) are widespread persistent environmental pollutants. There is evidence that PFAS induce metabolic perturbations in humans, but underlying mechanisms are still unknown. In this exploratory study, we investigated PFAS-related plasma metabolites for their associations with type 2 diabetes (T2D) to gain potential mechanistic insight in these perturbations. We used untargeted LC-MS metabolomics to find metabolites related to PFAS exposures in a case-control study on T2D (n = 187 matched pairs) nested within the Västerbotten Intervention Programme cohort. Following principal component analysis (PCA), six PFAS measured in plasma appeared in two groups: 1) perfluorononanoic acid, perfluorodecanoic acid and perfluoroundecanoic acid and 2) perfluorohexane sulfonic acid, perfluorooctane sulfonic acid and perfluorooctanoic acid. Using a random forest algorithm, we discovered metabolite features associated with individual PFAS and PFAS exposure groups which were subsequently investigated for associations with risk of T2D. PFAS levels correlated with 171 metabolite features (0.16 ≤ |r| ≤ 0.37, false discovery rate (FDR) adjusted p < 0.05). Out of these, 35 associated with T2D (p < 0.05), with 7 remaining after multiple testing adjustment (FDR < 0.05). PCA of the 35 PFAS- and T2D-related metabolite features revealed two patterns, dominated by glycerophospholipids and diacylglycerols, with opposite T2D associations. The glycerophospholipids correlated positively with PFAS and associated inversely with risk for T2D (Odds Ratio (OR) per 1 standard deviation (1-SD) increase in metabolite PCA pattern score = 0.2; 95% Confidence Interval (CI) = 0.1–0.4). The diacylglycerols also correlated positively with PFAS, but they associated with increased risk for T2D (OR per 1-SD = 1.9; 95% CI = 1.3–2.7). These results suggest that PFAS associate with two groups of lipid species with opposite relations to T2D risk.
|
|
| 18. |
- U-Din, Mueez, et al.
(författare)
-
Cold-stimulated brown adipose tissue activation is related to changes in serum metabolites relevant to NAD + metabolism in humans
- 2023
-
Ingår i: Cell Reports. - 2211-1247. ; 42:9
-
Tidskriftsartikel (refereegranskat)abstract
- Cold-induced brown adipose tissue (BAT) activation is considered to improve metabolic health. In murine BAT, cold increases the fundamental molecule for mitochondrial function, nicotinamide adenine dinucleotide (NAD+), but limited knowledge of NAD+ metabolism during cold in human BAT metabolism exists. We show that cold increases the serum metabolites of the NAD+ salvage pathway (nicotinamide and 1-methylnicotinamide) in humans. Additionally, individuals with cold-stimulated BAT activation have decreased levels of metabolites from the de novo NAD+ biosynthesis pathway (tryptophan, kynurenine). Serum nicotinamide correlates positively with cold-stimulated BAT activation, whereas tryptophan and kynurenine correlate negatively. Furthermore, the expression of genes involved in NAD+ biosynthesis in BAT is related to markers of metabolic health. Our data indicate that cold increases serum tryptophan conversion to nicotinamide to be further utilized by BAT. We conclude that NAD+ metabolism is activated upon cold in humans and is probably regulated in a coordinated fashion by several tissues.
|
|
| 19. |
- Vitale, Marilena, et al.
(författare)
-
Putative metabolites involved in the beneficial effects of wholegrain cereal: Nontargeted metabolite profiling approach
- 2021
-
Ingår i: Nutrition, Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 31:4, s. 1156-1165
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Wholegrain cereals have been implicated in the reduction of lifestyle-related chronic diseases risk including cardiovascular diseases and type 2 diabetes. Molecular mechanisms responsible for the beneficial health effects are not entirely understood. The aims of this study were 1) to identify new potential plasma biomarker candidate metabolites of wholegrain cereal foods intake and 2) to examine whether some putative metabolites associated with wholegrain foods intake may play a role in the improvement of cardiometabolic risk factors. Methods and results: Analysis have been conducted in 54 individuals with metabolic syndrome of both genders, age 40–65 years, randomly assigned to 2 dietary interventions lasting 12-week: 1) wholegrain enriched diet (n = 28), and 2) refined-wheat cereals diet (control diet) (n = 26). Nontargeted metabolite profiling analysis was performed on fasting plasma samples collected at baseline and at the end of the experimental diets. Our data show that, at the end of the intervention, a higher intake of wholegrain (tertile 3) was significantly associated with a marked increase in several lipid compounds, as PC (20:4/16:1), LPC (20:4), LPC (22:6), LPC (18:3), LPC (22:5), and a phenolic compound (P < .05 for all). In the wholegrain group, higher concentrations of these metabolites (tertile 3 vs tertile 1 of each metabolite) were significantly associated with lower postprandial insulin and triglyceride responses (P < .05) by 29% and 37%, respectively. Conclusion: These observations suggest a possible role of lipid and polyphenol metabolites in the postprandial metabolic benefits of wholegrains in subjects at high risk of cardiovascular disease. In addition, they provide insight into the role of these metabolites as potential candidate biomarkers of wholegrain foods. The study was registered on ClinicalTrials.gov (identifier: NCT00945854).
|
|
| 20. |
- Zhang, Pei, et al.
(författare)
-
Defining the Scope of Exposome Studies and Research Needs from a Multidisciplinary Perspective
- 2021
-
Ingår i: Environmental Science and Technology Letters. - : American Chemical Society (ACS). - 2328-8930. ; 8:10, s. 839-852
-
Forskningsöversikt (refereegranskat)abstract
- The concept of the exposome was introduced over 15 years ago to reflect the important role that the environment exerts on health and disease. While originally viewed as a call-to-arms to develop more comprehensive exposure assessment methods applicable at the individual level and throughout the life course, the scope of the exposome has now expanded to include the associated biological response. In order to explore these concepts, a workshop was hosted by the Gunma University Initiative for Advanced Research (GIAR, Japan) to discuss the scope of exposomics from an international and multidisciplinary perspective. This Global Perspective is a summary of the discussions with emphasis on (1) top-down, bottom-up, and functional approaches to exposomics, (2) the need for integration and standardization of LC- and GC-based high-resolution mass spectrometry methods for untargeted exposome analyses, (3) the design of an exposomics study, (4) the requirement for open science workflows including mass spectral libraries and public databases, (5) the necessity for large investments in mass spectrometry infrastructure in order to sequence the exposome, and (6) the role of the exposome in precision medicine and nutrition to create personalized environmental exposure profiles. Recommendations are made on key issues to encourage continued advancement and cooperation in exposomics.
|
|
