| 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. |
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| 3. |
- de Mello, Vanessa D., et al.
(författare)
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Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Wide-scale profiling technologies including metabolomics broaden the possibility of novel discoveries related to the pathogenesis of type 2 diabetes (T2D). By applying non-targeted metabolomics approach, we investigated here whether serum metabolite profile predicts T2D in a well-characterized study population with impaired glucose tolerance by examining two groups of individuals who took part in the Finnish Diabetes Prevention Study (DPS); those who either early developed T2D (n = 96) or did not convert to T2D within the 15-year follow-up (n = 104). Several novel metabolites were associated with lower likelihood of developing T2D, including indole and lipid related metabolites. Higher indolepropionic acid was associated with reduced likelihood of T2D in the DPS. Interestingly, in those who remained free of T2D, indolepropionic acid and various lipid species were associated with better insulin secretion and sensitivity, respectively. Furthermore, these metabolites were negatively correlated with low-grade inflammation. We replicated the association between indolepropionic acid and T2D risk in one Finnish and one Swedish population. We suggest that indolepropionic acid, a gut microbiota-produced metabolite, is a potential biomarker for the development of T2D that may mediate its protective effect by preservation of alpha-cell function. Novel lipid metabolites associated with T2D may exert their effects partly through enhancing insulin sensitivity.
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| 4. |
- de Mello, Vanessa D., et al.
(författare)
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Serum aromatic and branched-chain amino acids associated with NASH demonstrate divergent associations with serum lipids
- 2021
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Ingår i: Liver International. - : Wiley. - 1478-3223 .- 1478-3231. ; 41:4, s. 754-763
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Non-alcoholic fatty liver disease (NAFLD) has been associated with multiple metabolic abnormalities. By applying a non-targeted metabolomics approach, we aimed at investigating whether serum metabolite profile that associates with NAFLD would differ in its association with NAFLD-related metabolic risk factors. Methods & Results: A total of 233 subjects (mean ± SD: 48.3 ± 9.3 years old; BMI: 43.1 ± 5.4 kg/m2; 64 male) undergoing bariatric surgery were studied. Of these participants, 164 with liver histology could be classified as normal liver (n = 79), simple steatosis (SS, n = 40) or non-alcoholic steatohepatitis (NASH, n = 45). Among the identified fasting serum metabolites with higher levels in those with NASH when compared to those with normal phenotype were the aromatic amino acids (AAAs: tryptophan, tyrosine and phenylalanine), the branched-chain amino acids (BCAAs: leucine and isoleucine), a phosphatidylcholine (PC(16:0/16:1)) and uridine (all FDRp < 0.05). Only tryptophan was significantly higher in those with NASH compared to those with SS (FDRp < 0.05). Only the AAAs tryptophan and tyrosine correlated positively with serum total and LDL cholesterol (FDRp < 0.1), and accordingly, with liver LDLR at mRNA expression level. In addition, tryptophan was the single AA associated with liver DNA methylation of CpG sites known to be differentially methylated in those with NASH. Conclusions: We found that serum levels of the NASH-related AAAs and BCAAs demonstrate divergent associations with serum lipids. The specific correlation of tryptophan with LDL-c may result from the molecular events affecting LDLR mRNA expression and NASH-associated methylation of genes in the liver.
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| 5. |
- 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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| 6. |
- Hanhineva, Kati, 1972
(författare)
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Application of Metabolomics for the Assessment of Health Effects of Whole grain Foods
- 2021
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Ingår i: Whole Grains and Health: Second Edition. - : Wiley. ; , s. 375-388
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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.
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| 7. |
- Hanhineva, Kati, et al.
(författare)
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Discovery of urinary biomarkers of whole grain rye intake in free-living subjects using non-targeted LC-MS metabolite profiling
- 2015
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Ingår i: Molecular Nutrition & Food Research. - : Wiley. - 1613-4125 .- 1613-4133. ; 59:11, s. 2315-2325
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Tidskriftsartikel (refereegranskat)abstract
- SCOPE: Whole grain (WG) intake is associated with decreased risk of developing colorectal cancer, type 2 diabetes and cardiovascular disease and its comorbidities. However, the role of specific grains is unclear. Moreover, intake of specific WG is challenging to measure accurately with traditional dietary assessment methods. Our aim was to use non-targeted metabolite profiling to discover specific urinary biomarkers for WG rye to objectively reflect intake under free-living conditions.METHODS AND RESULTS: WG rye intake was estimated by weighed food records, and 24 h urine collections were analyzed by LC-MS. Multivariate modelling was undertaken by repeated double cross-validated partial least squares regression against reported WG rye intake, which correlated well with multivariate prediction estimates (r = 0.67-0.80, p<0.001), but not with intakes of WG wheat or oats. Hydroxyhydroxyphenyl acetamide (HHPA) sulfate, 3,5-dihydroxyphenylpropionic acid (DHPPA) sulfate, caffeic acid sulfate and hydroxyphenyl acetamide (HPAA) sulfate were among the 20 features which had the greatest potential as intake biomarkers of WG. In addition, three compounds exhibited MS/MS fragmentation of carnitine structures.CONCLUSION: With this non-targeted approach, we confirmed the specificity of alkylresorcinol metabolites as biomarkers for WG rye intake, but also discovered other compounds that should be evaluated as putative biomarkers in future studies.
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| 8. |
- 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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| 9. |
- 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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| 10. |
- Koistinen, Ville M., et al.
(författare)
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Metabolite pattern derived from Lactiplantibacillus plantarum : fermented rye foods and in vitro gut fermentation synergistically inhibits bacterial growth
- 2022
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Ingår i: Molecular Nutrition & Food Research. - : John Wiley & Sons. - 1613-4125 .- 1613-4133. ; 66:21
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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.
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