| 1. |
- Ahmed, Hany, et al.
(författare)
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Microbiota-derived metabolites as drivers of gut–brain communication
- 2022
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Ingår i: Gut Microbes. - : Informa UK Limited. - 1949-0984 .- 1949-0976. ; 14:1
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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.
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| 2. |
- Haikonen, Retu, et al.
(författare)
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Diet- and microbiota-related metabolite, 5-aminovaleric acid betaine (5-AVAB), in health and disease
- 2022
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Ingår i: Trends in Endocrinology and Metabolism. - : Elsevier BV. - 1879-3061 .- 1043-2760. ; 33:7, s. 463-480
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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.
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| 3. |
- 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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| 4. |
- Koistinen, Ville Mikael, et al.
(författare)
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Interlaboratory coverage test on plant food bioactive compounds and their metabolites by mass spectrometry-based untargeted metabolomics
- 2018
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989 .- 2218-1989. ; 8:3
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Tidskriftsartikel (refereegranskat)abstract
- Bioactive compounds present in plant-based foods, and their metabolites derived from gut microbiota and endogenous metabolism, represent thousands of chemical structures of potential interest for human nutrition and health. State-of-the-art analytical methodologies, including untargeted metabolomics based on high-resolution mass spectrometry, are required for the profiling of these compounds in complex matrices, including plant food materials and biofluids. The aim of this project was to compare the analytical coverage of untargeted metabolomics methods independently developed and employed in various European platforms. In total, 56 chemical standards representing the most common classes of bioactive compounds spread over a wide chemical space were selected and analyzed by the participating platforms (n = 13) using their preferred untargeted method. The results were used to define analytical criteria for a successful analysis of plant food bioactives. Furthermore, they will serve as a basis for an optimized consensus method.
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| 5. |
- Koistinen, Ville Mikael, et al.
(författare)
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Metabolic changes in response to varying whole-grain wheat and rye intake
- 2024
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Ingår i: npj Science of Food. - 2396-8370. ; 8:1
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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.
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| 6. |
- Koistinen, Ville Mikael, et al.
(författare)
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Side-stream products of malting: a neglected source of phytochemicals
- 2020
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Ingår i: npj Science of Food. - : Springer Science and Business Media LLC. - 2396-8370. ; 4:1
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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.
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| 7. |
- 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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| 8. |
- Low, Dorrain Yanwen, et al.
(författare)
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Data sharing in PredRet for accurate prediction of retention time: Application to plant food bioactive compounds
- 2021
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Ingår i: Food Chemistry. - : Elsevier BV. - 0308-8146 .- 1873-7072. ; 357
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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.
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| 9. |
- 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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| 10. |
- Vitale, Marilena, et al.
(författare)
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Putative metabolites involved in the beneficial effects of wholegrain cereal: Nontargeted metabolite profiling approach
- 2021
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Ingår i: Nutrition, Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 31:4, s. 1156-1165
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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).
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| 11. |
- Zhang, Pei, et al.
(författare)
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Defining the Scope of Exposome Studies and Research Needs from a Multidisciplinary Perspective
- 2021
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Ingår i: Environmental Science and Technology Letters. - : American Chemical Society (ACS). - 2328-8930. ; 8:10, s. 839-852
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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.
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