| 1. |
- Kmezik, Cathleen, 1991, et al.
(författare)
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A polysaccharide utilization locus from the gut bacterium Dysgonomonas mossii encodes functionally distinct carbohydrate esterases.
- 2021
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Ingår i: The Journal of biological chemistry. - : Elsevier BV. - 1083-351X .- 0021-9258. ; 296
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Tidskriftsartikel (refereegranskat)abstract
- The gut microbiota plays a central role in human health by enzymatically degrading dietary fiber and concomitantly excreting short chain fatty acids that are associated with manifold health benefits. The polysaccharide xylan is abundant in dietary fiber but non-carbohydrate decorations hinder efficient cleavage by glycoside hydrolases (GHs) and need to be addressed by carbohydrate esterases (CEs). Enzymes from carbohydrate esterase families 1 and 6 (CE1 & 6) perform key roles in xylan degradation by removing feruloyl and acetate decorations, yet little is known about these enzyme families especially with regards to their diversity in activity. Bacteroidetes bacteria are dominant members of the microbiota and often encode their carbohydrate-active enzymes in multi-gene polysaccharide utilization loci (PULs). Here we present the characterization of three CEs found in a PUL encoded by the gut Bacteroidete Dysgonomonas mossii. We demonstrate that the CEs are functionally distinct, with one highly efficient CE6 acetyl esterase and two CE1 enzymes with feruloyl esterase activities. One multidomain CE1 enzyme contains two CE1 domains: an N-terminal domain feruloyl esterase, and a C-terminal domain with minimal activity on model substrates. We present the structure of the C-terminal CE1 domain with the carbohydrate binding module that bridges the two CE1 domains, as well as a complex of the same protein fragment with methyl ferulate. The investment of D. mossii in producing multiple CEs suggests that improved accessibility of xylan for GHs as well as cleavage of covalent polysaccharide-polysaccharide and lignin-polysaccharide bonds are important enzyme activities in the gut environment.
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| 2. |
- Tyumentsev, Mikhail S, 1988, et al.
(författare)
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Coordination of Trivalent Lanthanides with Bismalonamide Ligands: Implications for Liquid-Liquid Extraction
- 2017
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Ingår i: European Journal of Inorganic Chemistry. - : Wiley. - 1434-1948 .- 1099-0682. ; 2017:37, s. 4285-4298
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Tidskriftsartikel (refereegranskat)abstract
- The complexation of the bismalonamide ligand 2,2'[1,2-phenylenebis(methylene)] bis(N, N, N', N'-tetraethylmalonamide) (L), bearing two C-alkylated N, N, N', N'-tetraethylmalonamide groups, onto an ortho-xylylene [C6H4(CH2)(2)] platform with trivalent lanthanides was investigated, both in solid and solution states. The crystal structures [Nd-2(NO3)(6)L-2]center dot(CH3CN)(3) (2), [Nd-2(NO3)(4)L-2]center dot[Nd(NO3)(5)]center dot(CH3CN) 1.5 (3), Ce(NO3)(3)L-2 (4), and [NdL2]center dot(ClO4)(3)center dot C2H5OH (5) were analyzed by single-crystal X-ray diffraction. The ortho-bismalonamide (L) is tetradentate in structures 2, 3, and 5 and bidentate in 4 only. It was found that structures 2 and 3 are composed of dimeric species. According to electrospray-ionization mass spectrometry, the dimers are prevailing in acetonitrile solutions. The polydentate coordination of the ortho-bismalonamide (L) with trivalent lanthanides suggests that an entropy effect favors liquid-liquid extraction of metal ions with this type of ligand.
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| 3. |
- Ahluwalia, Bani, et al.
(författare)
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A Distinct Faecal Microbiota and Metabolite Profile Linked to Bowel Habits in Patients with Irritable Bowel Syndrome
- 2021
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Patients with irritable bowel syndrome (IBS) are suggested to have an altered intestinal microenvironment. We therefore aimed to determine the intestinal microenvironment profile, based on faecal microbiota and metabolites, and the potential link to symptoms in IBS patients. The faecal microbiota was evaluated by the GA-map(TM) dysbiosis test, and tandem mass spectrometry (GC-MS/MS) was used for faecal metabolomic profiling in patients with IBS and healthy subjects. Symptom severity was assessed using the IBS Severity Scoring System and anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. A principal component analysis based on faecal microbiota (n = 54) and metabolites (n = 155) showed a clear separation between IBS patients (n = 40) and healthy subjects (n = 18). Metabolites were the main driver of this separation. Additionally, the intestinal microenvironment profile differed between IBS patients with constipation (n = 15) and diarrhoea (n = 11), while no clustering was detected in subgroups of patients according to symptom severity or anxiety. Furthermore, ingenuity pathway analysis predicted amino acid metabolism and several cellular and molecular functions to be altered in IBS patients. Patients with IBS have a distinct faecal microbiota and metabolite profile linked to bowel habits. Intestinal microenvironment profiling, based on faecal microbiota and metabolites, may be considered as a future non-invasive diagnostic tool, alongside providing valuable insights into the pathophysiology of IBS.
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| 4. |
- Ahluwalia, Bani, et al.
(författare)
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Differences in Metabolite Composition of Aloe barbadensis Mill. Extracts Lead to Differential Effects on Human Blood T Cell Activity In Vitro
- 2022
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Ingår i: Molecules. - : MDPI AG. - 1420-3049 .- 1420-3049. ; 27:19
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Tidskriftsartikel (refereegranskat)abstract
- Aloe barbadensis Mill. (Aloe) is used for diverse therapeutic properties including immunomodulation. However, owing to the compositionally complex nature of Aloe, bioactive component(s) responsible for its beneficial properties, though thought to be attributed to polysaccharides (acemannan), remain unknown. We therefore aimed to determine the metabolite composition of various commercial Aloe extracts and assess their effects on human blood T cell activity in vitro. Peripheral blood mononuclear cells (PBMC) from healthy donors were stimulated polyclonally in presence or absence of various Aloe extracts. T cell phenotype and proliferation were investigated by flow cytometry. Aloe extracts were analyzed using targeted 1H-NMR spectroscopy for standard phytochemical quality characterization and untargeted gas chromatography mass spectrometry (GC-MS) for metabolite profiling. Aloe extracts differing in their standard phytochemical composition had varying effects on T cell activation, proliferation, apoptosis, and cell-death in vitro, although this was not related to the acemannan content. Furthermore, each Aloe extract had its own distinct metabolite profile, where extracts rich in diverse sugar and sugar-derivatives were associated with reduced T cell activity. Our results demonstrate that all commercial Aloe extracts are unique with distinct metabolite profiles, which lead to differential effects on T cell activity in vitro, independent of the acemannan content.
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| 5. |
- Ahluwalia, Bani, et al.
(författare)
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Randomized clinical trial: Effects of Aloe barbadensis Mill. extract on symptoms, fecal microbiota and fecal metabolite profiles in patients with irritable bowel syndrome
- 2020
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 32:8
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Tidskriftsartikel (refereegranskat)abstract
- Background Aloe barbadensis Mill.(Aloe) with potential prebiotic effects has been suggested to reduce symptoms in patients with irritable bowel syndrome (IBS). We therefore aimed to determine the effects of an Aloe extract on symptoms of IBS, and evaluate whether effects may be mediated by fecal microbiota and metabolites in a randomized, double-blind, controlled trial. Methods Patient with IBS diagnosed according to the ROME III criteria (all subtypes), received Aloe or control treatment (inulin) for 4 weeks. IBS Symptom Severity Score (IBS-SSS) was assessed, and fecal samples collected before and at end of treatment. Fecal microbiota composition and metabolomic profile were determined. Key results In total, 160 IBS patients completed the study. The overall severity of IBS symptoms was reduced in both Aloe and control treatment groups (P < .001, both groups, comparing baseline vs end of treatment), without difference between groups (P = .62). The frequency of responders (IBS-SSS reduction >= 50) did not differ between Aloe treatment (n = 33, 39%) and control (n = 34, 45%) (P = .49). However, fecal microbiota and metabolite profiles differed between Aloe, but not control treatment responders and non-responders both before and after treatment. Conclusion In a mixed group of IBS patients, Aloe was not superior to control treatment, although it showed potential to reduce IBS symptom severity in subsets of IBS patients which could be predicted by fecal microbiota and metabolite profiles. ClinicalTrials.gov no: NCT01400048.
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| 6. |
- Brunnsåker, Daniel, 1992, et al.
(författare)
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High-throughput metabolomics for the design and validation of a diauxic shift model
- 2023
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Ingår i: NPJ systems biology and applications. - : Springer Nature. - 2056-7189. ; 9:1, s. 11-
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Tidskriftsartikel (refereegranskat)abstract
- Saccharomyces cerevisiae is a very well studied organism, yet ∼20% of its proteins remain poorly characterized. Moreover, recent studies seem to indicate that the pace of functional discovery is slow. Previous work has implied that the most probable path forward is via not only automation but fully autonomous systems in which active learning is applied to guide high-throughput experimentation. Development of tools and methods for these types of systems is of paramount importance. In this study we use constrained dynamical flux balance analysis (dFBA) to select ten regulatory deletant strains that are likely to have previously unexplored connections to the diauxic shift. We then analyzed these deletant strains using untargeted metabolomics, generating profiles which were then subsequently investigated to better understand the consequences of the gene deletions in the metabolic reconfiguration of the diauxic shift. We show that metabolic profiles can be utilised to not only gaining insight into cellular transformations such as the diauxic shift, but also on regulatory roles and biological consequences of regulatory gene deletion. We also conclude that untargeted metabolomics is a useful tool for guidance in high-throughput model improvement, and is a fast, sensitive and informative approach appropriate for future large-scale functional analyses of genes. Moreover, it is well-suited for automated approaches due to relative simplicity of processing and the potential to make massively high-throughput.
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| 7. |
- Choung, Rok Seon, et al.
(författare)
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Community-Based Study of Celiac Disease Autoimmunity Progression in Adults
- 2020
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Ingår i: Gastroenterology. - : Elsevier BV. - 1528-0012 .- 0016-5085. ; 158:1, s. 151-159
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: Celiac disease can develop at any age, but outcomes of adults with positive results from serologic tests for tissue transglutaminase antibodies (tTGA) without endoscopic determination of celiac disease (called celiac autoimmunity) have not been thoroughly evaluated. We investigated the proportion of adults with celiac autoimmunity at a community medical center and their progression to celiac disease. Methods: We analyzed waste blood samples from a community clinic from 15,551 adults for tTGA and, if titer results were above 2 U/mL, for endomysial antibody. The blood samples had been collected at 2 time points (median interval, 8.8 years) from 2006 through 2017. We collected data from the clinic on diagnoses of celiac disease based on duodenal biopsy analysis. Results: Of the serum samples collected at the first time point, 15,398 had negative results for tTGA, and 153 had positive results for tTGA (>4 U/mL). Based on medical records, 6 individuals received a diagnosis of celiac disease, for a cumulative incidence of celiac disease diagnosis of 0.06% (95% confidence interval, 0.01–0.11). Forty-nine (0.32%) individuals with a negative result from the first serologic test for tTGA had a positive result from the second test. Among the 153 adults who were tTGA positive at the first time point, 31 (20%) had a subsequent diagnosis of celiac disease, 81 (53%) remained positive for tTGA without a clinical diagnosis of celiac disease, and 41 (27%) had negative test results for tTGA at the second time point. Higher initial tTGA titers, female sex, and a history of hypothyroidism and autoimmune disease were associated with increased risks of subsequent diagnosis of celiac disease. Interestingly, adults whose first blood sample had a positive test result but second blood sample had a negative result for tTGA were older, had lower-than-average initial tTGA titer results, and had a higher mean body mass index than adults whose blood samples were positive for tTGA at both time points and adults later diagnosed with celiac disease. Conclusions: In an analysis of serum samples collected from a community clinic an average of 8.8 years apart, we found that fewer than 1% of adults with negative results from an initial test for tTGA have a positive result on a second test. Of adults with positive results from the test for tTGA, only 20% are later diagnosed with celiac disease; the remaining individuals maintain persistent increases in tTGA without diagnoses of celiac disease or have negative results from second tests.
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| 8. |
- Churqui, Marianela Patzi, 1987, et al.
(författare)
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Extracts of Equisetum giganteum L and Copaifera reticulate Ducke show strong antiviral activity against the sexually transmitted pathogen herpes simplex virus type 2
- 2018
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Ingår i: Journal of Ethnopharmacology. - : Elsevier BV. - 0378-8741 .- 1872-7573. ; 210, s. 192-197
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Tidskriftsartikel (refereegranskat)abstract
- Ethnopharmacological relevance Equisetum giganteum L and Copaifera reticulate Ducke have been traditionally used by women of the Tacana tribe in the Bolivian Amazonas for genital hygiene and for treatment of genital infection/inflammation. Aim of the study To assess the ability of extracts from Equisetum giganteum L and Copaifera reticulate Ducke to block genital viral infection by herpes simplex virus type 2. Materials and Methods Equisetum giganteum L and Copaifera reticulate Ducke were collected from the Amazon region of La Paz, Bolivia. Extracts were prepared and screened for anti-viral activity against herpes simplex virus type 2 (HSV-2) using both in vitro and in in vivo models of infection. Results Equisetum giganteum L and Copaifera reticulate Ducke efficiently blocked HSV-2 infection of cell cultures without major cell cytotoxic effects. Extracts of Equisetum giganteum L and Copaifera reticulate Ducke could prevent HSV-2 disease development when administered together with virus in a mouse model of genital HSV-2 infection. In vitro analyses revealed that both plant extracts exerted their anti-HSV-2 effects by interfering with viral cell attachment and entry, but could not block viral replication post entry. Conclusions These studies show that extracts of Equisetum giganteum L and Copaifera reticulate Ducke have potent antiviral activities against HSV-2 comparable to those two previously identified plants, Croton lechleri Müll. Arg. and Uncaria tomentosa (Willd. ex Schult.) DC. These studies confirm that plants used by the Tacana tribe could be explored further for the development of novel topical antiviral microbicides. © 2017 Elsevier Ireland Ltd
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| 9. |
- Dahlstrand Rudin, Agnes, et al.
(författare)
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Porphyromonas gingivalis Produce Neutrophil Specific Chemoattractants Including Short Chain Fatty Acids
- 2021
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Ingår i: Frontiers in cellular and infection microbiology. - : Frontiers Media SA. - 2235-2988. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Neutrophil migration from blood to tissue-residing microbes is governed by a series of chemoattractant gradients of both endogenous and microbial origin. Periodontal disease is characterized by neutrophil accumulation in the gingival pocket, recruited by the subgingival biofilm consisting mainly of gram-negative, anaerobic and proteolytic species such as Porphyromonas gingivalis. The fact that neutrophils are the dominating cell type in the gingival pocket suggests that neutrophil-specific chemoattractants are released by subgingival bacteria, but characterization of chemoattractants released by subgingival biofilm species remains incomplete. In the present study we characterized small (< 3 kDa) soluble chemoattractants released by growing P. gingivalis, and show that these are selective for neutrophils. Most neutrophil chemoattractant receptors are expressed also by mononuclear phagocytes, the free fatty acid receptor 2 (FFAR2) being an exception. In agreement with the selective neutrophil recruitment, the chemotactic activity found in P. gingivalis supernatants was mediated in part by a mixture of short chain fatty acids (SCFAs) that are recognized by FFAR2, and other leukocytes (including monocytes) did not respond to SCFA stimulation. Although SCFAs, produced by bacterial fermentation of dietary fiber in the gut, has previously been shown to utilize FFAR2, our data demonstrate that the pronounced proteolytic metabolism employed by P. gingivalis (and likely also other subgingival biofilm bacteria associated with periodontal diseases) may result in the generation of SCFAs that attract neutrophils to the gingival pocket. This finding highlights the interaction between SCFAs and FFAR2 in the context of P. gingivalis colonization during periodontal disease, but may also have implications for other inflammatory pathologies involving proteolytic bacteria.
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| 10. |
- Dihm, Katharina, 1990, et al.
(författare)
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Quantification of benzoxazinoids and their metabolites in Nordic breads
- 2017
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Ingår i: Food Chemistry. - : Elsevier BV. - 0308-8146 .- 1873-7072. ; 235, s. 7-13
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Tidskriftsartikel (refereegranskat)abstract
- Benzoxazinoids (Bx) and their metabolites are molecules with suggested health effects in humans, found in cereal grains and consequently in cereal foods. However, to date little is known about the amount of Bx in our diet. In this study, deuterated standards 2-hydroxy-1,4-benzoxazin-3-one (HBOA-d4) and 2-hydroxy-N-(2-hydroxyphenyl) acetamide (HHPAA-d4) were synthesized, to allow quantification of nine Bx and their metabolites in 30 breads and flours from Nordic countries by UHPLC-MS/MS. Samples containing rye had larger amounts of Bx (143–3560 µg/g DM) than the ones containing wheat (11–449 µg/g DM). More Bx were found in whole grain wheat (57–449 µg/g DM) compared to refined wheat (11–92 µg/g DM) breads. Finnish sourdough rye breads were notably high in their 2-hydroxy-N-(2-hydroxyphenyl) acetamide (HHPAA) concentration (40–48 µg/g DM). This new information on Bx content in flours and breads available in the Nordic countries will be useful for future work on determining dietary exposure to Bx.
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| 11. |
- Djekic, Demir, 1989-, et al.
(författare)
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Effects of a Vegetarian Diet on Cardiometabolic Risk Factors, Gut Microbiota, and Plasma Metabolome in Subjects With Ischemic Heart Disease: A Randomized, Crossover Study
- 2020
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Ingår i: Journal of the American Heart Association. - : Wiley-Blackwell Publishing Inc.. - 2047-9980. ; 9:18, s. e016518-e016518
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Tidskriftsartikel (refereegranskat)abstract
- Background A vegetarian diet (VD) may reduce future cardiovascular risk in patients with ischemic heart disease. Methods and Results A randomized crossover study was conducted in subjects with ischemic heart disease, assigned to 4-week intervention periods of isocaloric VD and meat diet (MD) with individually designed diet plans, separated by a 4-week washout period. The primary outcome was difference in oxidized low-density lipoprotein cholesterol (LDL-C) between diets. Secondary outcomes were differences in cardiometabolic risk factors, quality of life, gut microbiota, fecal short-chain and branched-chain fatty acids, and plasma metabolome. Of 150 eligible patients, 31 (21%) agreed to participate, and 27 (87%) participants completed the study. Mean oxidized LDL-C (-2.73 U/L), total cholesterol (-5.03 mg/dL), LDL-C (-3.87 mg/dL), and body weight (-0.67 kg) were significantly lower with the VD than with the MD. Differences between VD and MD were observed in the relative abundance of several microbe genera within the families Ruminococcaceae, Lachnospiraceae, and Akkermansiaceae. Plasma metabolites, including l-carnitine, acylcarnitine metabolites, and phospholipids, differed in subjects consuming VD and MD. The effect on oxidized LDL-C in response to the VD was associated with a baseline gut microbiota composition dominated by several genera of Ruminococcaceae. Conclusions The VD in conjunction with optimal medical therapy reduced levels of oxidized LDL-C, improved cardiometabolic risk factors, and altered the relative abundance of gut microbes and plasma metabolites in patients with ischemic heart disease. Our results suggest that composition of the gut microbiota at baseline may be related to the reduction of oxidized LDL-C observed with the VD. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02942628.
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| 12. |
- González-Domínguez, Álvaro, et al.
(författare)
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Untargeted Metabolomics Based on Liquid Chromatography-Mass Spectrometry for the Analysis of Plasma and Erythrocyte Samples in Childhood Obesity
- 2023
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Ingår i: Methods in Molecular Biology. - New York, NY : Springer US. - 1940-6029 .- 1064-3745. ; , s. 115-122
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The circulating metabolome of human peripheral blood provides valuable information to investigate the molecular mechanisms underlying the development of diseases and to discover candidate biomarkers. In particular, erythrocytes have been proposed as potential systemic indicators of the metabolic and redox status of the organism. To accomplish wide-coverage metabolomics analysis, the combination of complementary analytical techniques is necessary to manage the physicochemical complexity of the human metabolome. Herein, we describe an untargeted metabolomics method to capture the plasmatic and erythroid metabolomes based on ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry, combining reversed-phase liquid chromatography and hydrophilic interaction liquid chromatography. The method provides comprehensive metabolomics fingerprinting of plasma and erythrocyte samples, thereby enabling the elucidation of the distinctive metabolic disturbances behind childhood obesity and associated comorbidities, such as insulin resistance.
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| 13. |
- Gorreja, Frida, et al.
(författare)
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Fecal Supernatants from Patients with Crohn's Disease Induce Inflammatory Alterations in M2 Macrophages and Fibroblasts
- 2024
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Ingår i: CELLS. - 2073-4409. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Intestinal macrophages and fibroblasts act as microenvironmental sentinels mediating inflammation and disease progression in Crohn's disease (CD). We aimed to establish the effects of fecal supernatants (FSs) from patients with CD on macrophage and fibroblast phenotype and function. FS were obtained by ultracentrifugation, and the metabolites were analyzed. Monocyte-derived M2 macrophages and fibroblasts were conditioned with FS, and secreted proteins, surface proteins and gene expression were analyzed. M2 macrophage efferocytosis was evaluated. Patients with CD (n = 15) had a skewed fecal metabolite profile compared to healthy subjects (HS, n = 10). FS from CD patients (CD-FS) induced an anti-inflammatory response in M2 macrophages with higher expression of IL-10, IL1RA and CD206 as compared to healthy FS (HS-FS) while the efferocytotic capacity was unaltered. CD-FS did not affect extracellular matrix production from fibroblasts, but increased expression of the pro-inflammatory proteins IL-6 and MCP-1. Conditioned media from M2 macrophages treated with CD-FS modulated gene expression in fibroblasts for TGF beta superfamily members and reduced IL-4 expression compared to HS-FS. We show that M2 macrophages and fibroblasts react abnormally to the fecal microenvironment of CD patients, resulting in altered protein expression related to inflammation but not fibrosis. This implies that the gut microbiota and its metabolites have an important role in the generation and/or perpetuation of inflammation in CD.
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| 14. |
- Hallingström, Maria, et al.
(författare)
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Metabolomic profiles of mid-trimester amniotic fluid are not associated with subsequent spontaneous preterm delivery or gestational duration at delivery
- 2022
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Ingår i: Journal of Maternal-Fetal and Neonatal Medicine. - : Informa UK Limited. - 1476-7058 .- 1476-4954. ; 35:11, s. 2054-2062
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Tidskriftsartikel (refereegranskat)abstract
- Introduction:Spontaneous preterm delivery (<37 gestational weeks) has a multifactorial etiology with still incompletely identified pathways. Amniotic fluid is a biofluid with great potential for insights into the feto-maternal milieu. It is rich in metabolites, and metabolic consequences of inflammation is yet researched only to a limited extent. Metabolomic profiling provides opportunities to identify potential biomarkers of inflammatory conditioned pregnancy complications such as spontaneous preterm delivery. Objective:The aim of this study was to perform metabolomic profiling of amniotic fluid from uncomplicated singleton pregnancies in the mid-trimester to identify potential biomarkers associated with spontaneous preterm delivery and gestational duration at delivery. A secondary aim was to replicate previously reported mid-trimester amniotic fluid metabolic biomarkers of spontaneous preterm delivery in asymptomatic women. Method:A nested case-control study was performed within a larger cohort study of asymptomatic pregnant women undergoing mid-trimester genetic amniocentesis at 14-19 gestational weeks in Gothenburg, Sweden. Medical records were used to obtain clinical data and delivery outcome variables. Amniotic fluid samples from women with a subsequent spontaneous preterm delivery (n = 37) were matched with amniotic fluid samples from women with a subsequent spontaneous delivery at term (n = 37). Amniotic fluid samples underwent untargeted metabolomic analyses using liquid chromatography-mass spectrometry. Multivariate random forest analyses were used for data processing. A secondary targeted analysis was performed, aiming to replicate previously reported mid-trimester amniotic fluid metabolic biomarkers in women with a subsequent spontaneous preterm delivery. Results:Multivariate analysis did not distinguish the samples from women with a subsequent spontaneous preterm delivery from those with a subsequent term delivery. Neither was the metabolic profile associated with gestational duration at delivery. Potential metabolic biomarker candidates were identified from four publications by two different research groups relating mid-trimester amniotic fluid metabolomes to spontaneous PTD, of which fifteen markers were included in the secondary analysis. None of these were replicated. Conclusions:Metabolomic profiles of early mid-trimester amniotic fluid were not associated with spontaneous preterm delivery or gestational duration at delivery in this cohort.
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| 15. |
- Hartvigsson, Olle, 1991, et al.
(författare)
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Differences between Arterial and Venous Umbilical Cord Plasma Metabolome and Association with Parity
- 2022
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989 .- 2218-1989. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Umbilical cord blood is frequently used in health monitoring of the neonate. Results may be affected by the proportion of arterial and venous cord blood, the venous blood coming from the mother to supply oxygen and nutrients to the infant, and the arterial carrying waste products from the fetus. Here, we sampled arterial and venous umbilical cords separately from 48 newly delivered infants and examined plasma metabolomes using GC-MS/MS metabolomics. We investigated differences in metabolomes between arterial and venous blood and their associations with gestational length, birth weight, sex, and whether the baby was the first born or not, as well as maternal age and BMI. Using multilevel random forest analysis, a classification rate of 79% was achieved for arteriovenous differences (p = 0.004). Several monosaccharides had higher concentrations in the arterial cord plasma while amino acids were higher in venous plasma, suggesting that the main differences in the measured arterial and venous plasma metabolomes are related to amino acid and energy metabolism. Venous cord plasma metabolites related to energy metabolism were positively associated with parity (77% classification rate, p = 0.004) while arterial cord plasma metabolites were not. This underlines the importance of defining cord blood type for metabolomic studies.
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| 16. |
- Iribarren, Cristina, 1993, et al.
(författare)
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Fecal luminal factors from patients with irritable bowel syndrome induce distinct gene expression of colonoids
- 2022
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Ingår i: Neurogastroenterology and Motility. - : Wiley. - 1350-1925 .- 1365-2982. ; 34:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alteration of the host-microbiota cross talk at the intestinal barrier may participate in the pathophysiology of irritable bowel syndrome (IBS). Therefore, we aimed to determine effects of fecal luminal factors from IBS patients on the colonic epithelium using colonoids. Methods: Colon-derived organoid monolayers, colonoids, generated from a healthy subject, underwent stimulation with fecal supernatants from healthy subjects and IBS patients with predominant diarrhea, phosphate-buffered saline (PBS), or lipopolysaccharide (LPS). Cytokines in cell cultures and fecal LPS were measured by ELISA and mRNA gene expression of monolayers was analyzed using Qiagen RT2 Profiler PCR Arrays. The fecal microbiota profile was determined by the GA-map (TM) dysbiosis test and the fecal metabolite profile was analyzed by untargeted liquid chromatography/mass spectrometry. Key results: Colonoid monolayers stimulated with fecal supernatants from healthy subjects (n = 7), PBS (n = 4) or LPS (n = 3) presented distinct gene expression profiles, with some overlap ((RY)-Y-2 = 0.70, Q(2) = 0.43). Addition of fecal supernatants from healthy subjects and IBS patients (n = 9) gave rise to different gene expression profiles of the colonoid monolayers ((RY)-Y-2 = 0.79, Q(2) = 0.64). Genes (n = 22) related to immune response (CD1D, TLR5) and barrier integrity (CLDN15, DSC2) contributed to the separation. Levels of proinflammatory cytokines in colonoid monolayer cultures were comparable when stimulated with fecal supernatants from either donor types. Fecal microbiota and metabolite profiles, but not LPS content, differed between the study groups. Conclusions: Fecal luminal factors from IBS patients induce a distinct colonic epithelial gene expression, potentially reflecting the disease pathophysiology. The culture of colonoids from healthy subjects with fecal supernatants from IBS patients may facilitate the exploration of IBS related intestinal micro-environmental and barrier interactions.
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| 17. |
- Iribarren, Cristina, 1993, et al.
(författare)
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Temporal stability of fecal metabolomic profiles in irritable bowel syndrome
- 2024
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Ingår i: Neurogastroenterology and Motility. - 1350-1925 .- 1365-2982. ; 36:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: The potential of the fecal metabolome to serve as a biomarker for irritable bowel syndrome (IBS) depends on its stability over time. Therefore, this study aimed to determine the temporal dynamics of the fecal metabolome, and the potential relationship with stool consistency, in patients with IBS and healthy subjects. Methods: Fecal samples were collected in two cohorts comprising patients with IBS and healthy subjects. For Cohort A, fecal samples collected during 5 consecutive days were analyzed by gas chromatography-tandem mass spectrometry (GC–MS/MS). For Cohort B, liquid chromatography-MS (LC–MS) was used to analyze fecal samples collected at week 0 (healthy and IBS) and at week 4 (patients only). Stool consistency was determined by the Bristol Stool Form scale. Key Results: Fecal samples were collected from Cohort A (seven healthy subjects and eight IBS patients), and Cohort B (seven healthy subjects and 11 IBS patients). The fecal metabolome of IBS patients was stable short-term (Cohort A, 5 days and within the same day) and long-term (Cohort B, 4 weeks). A similar trend was observed over 5 days in the healthy subjects of Cohort A. The metabolome dissimilarity was larger between than within participants over time in both healthy subjects and IBS patients. Further analyses showed that patients had greater range of stool forms (types) than healthy subjects, with no apparent influence on metabolomic dynamics. Conclusion & Inferences: The fecal metabolome is stable over time within IBS patients as well as healthy subjects. This supports the concept of a stable fecal metabolome in IBS despite fluctuations in stool consistency, and the use of single timepoint sampling to further explore how the fecal metabolome is related to IBS pathogenesis.
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| 18. |
- 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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| 19. |
- 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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| 20. |
- 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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| 21. |
- Liu, Quanli, 1988, et al.
(författare)
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De novo biosynthesis of bioactive isoflavonoids by engineered yeast cell factories
- 2021
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Isoflavonoids comprise a class of plant natural products with great nutraceutical, pharmaceutical and agricultural significance. Their low abundance in nature and structural complexity however hampers access to these phytochemicals through traditional crop-based manufacturing or chemical synthesis. Microbial bioproduction therefore represents an attractive alternative. Here, we engineer the metabolism of Saccharomyces cerevisiae to become a platform for efficient production of daidzein, a core chemical scaffold for isoflavonoid biosynthesis, and demonstrate its application towards producing bioactive glucosides from glucose, following the screening-reconstruction-application engineering framework. First, we rebuild daidzein biosynthesis in yeast and its production is then improved by 94-fold through screening biosynthetic enzymes, identifying rate-limiting steps, implementing dynamic control, engineering substrate trafficking and fine-tuning competing metabolic processes. The optimized strain produces up to 85.4 mg L−1 of daidzein and introducing plant glycosyltransferases in this strain results in production of bioactive puerarin (72.8 mg L−1) and daidzin (73.2 mg L−1). Our work provides a promising step towards developing synthetic yeast cell factories for de novo biosynthesis of value-added isoflavonoids and the multi-phased framework may be extended to engineer pathways of complex natural products in other microbial hosts.
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| 22. |
- Maasfeh, Lujain, et al.
(författare)
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Impaired Luminal Control of Intestinal Macrophage Maturation in Patients With Ulcerative Colitis During Remission
- 2021
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Ingår i: Cellular and Molecular Gastroenterology and Hepatology. - : Elsevier BV. - 2352-345X. ; 12:4, s. 1415-1432
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND & AIMS: Intestinal macrophages adopt a hyporesponsive phenotype through education by local signals. Lack of proper macrophage maturation in patients with ulcerative colitis (UC) in remission may initiate gut inflammation. The aim, therefore, was to determine the effects of fecal luminal factors derived from healthy donors and UC patients in remission on macrophage phenotype and function. METHODS: Fecal supernatants (FS) were extracted from fecal samples of healthy subjects and UC patients in remission. Monocytes were matured into macrophages in the presence of granulocyte-macrophage colony-stimulating factor without/with FS, stimulated with lipopolysaccharide, and macrophage phenotype and function were assessed. Fecal metabolomic profiles were analyzed by gas-chromatography/mass-spectrometry. RESULTS: Fecal luminal factors derived from healthy donors were effective in down-regulating Toll-like receptor signaling, cytokine signaling, and antigen presentation in macrophages. Fecal luminal factors derived from UC patients in remission were less potent in inducing lipopolysaccharide hyporesponsiveness and modulating expression of genes involved in macrophage cytokine and Toll-like receptor signaling pathways. Although phagocytic and bactericidal abilities of macrophages were not affected by FS treatment, healthy FS-treated macrophages showed a greater ability to suppress cluster of differentiation 4(+) T-cell activation and interferon gamma secretion compared with UC remission FS-treated counterparts. Furthermore, metabolomic analysis showed differential fecal metabolite composition for healthy donors and UC patients in remission. CONCLUSIONS: Our data indicate that UC patients in remission lack luminal signals able to condition macrophages toward a hyporesponsive and tolerogenic phenotype, which may contribute to their persistent vulnerability to relapse.
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| 23. |
- Moraes Holst, Luiza, et al.
(författare)
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Fecal Luminal Factors from Patients with Gastrointestinal Diseases Alter Gene Expression Profiles in Caco-2 Cells and Colonoids
- 2022
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1422-0067 .- 1661-6596. ; 23:24
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Tidskriftsartikel (refereegranskat)abstract
- Previous in vitro studies have shown that the intestinal luminal content, including metabolites, possibly regulates epithelial layer responses to harmful stimuli and promotes disease. Therefore, we aimed to test the hypothesis that fecal supernatants from patients with colon cancer (CC), ulcerative colitis (UC) and irritable bowel syndrome (IBS) contain distinct metabolite profiles and establish their effects on Caco-2 cells and human-derived colon organoids (colonoids). The metabolite profiles of fecal supernatants were analyzed by liquid chromatography-mass spectrometry and distinguished patients with CC (n = 6), UC (n = 6), IBS (n = 6) and healthy subjects (n = 6). Caco-2 monolayers and human apical-out colonoids underwent stimulation with fecal supernatants from different patient groups and healthy subjects. Their addition did not impair monolayer integrity, as measured by transepithelial electrical resistance; however, fecal supernatants from different patient groups and healthy subjects altered the gene expression of Caco-2 monolayers, as well as colonoid cultures. In conclusion, the stimulation of Caco-2 cells and colonoids with fecal supernatants derived from CC, UC and IBS patients altered gene expression profiles, potentially reflecting the luminal microenvironment of the fecal sample donor. This experimental approach allows for investigating the crosstalk at the gut barrier and the effects of the gut microenvironment in the pathogenesis of intestinal diseases.
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| 24. |
- Näätänen, Mari, et al.
(författare)
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Metabolic profiles reflect weight loss maintenance and the composition of diet after very-low-energy diet
- 2023
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Ingår i: Clinical Nutrition. - 1532-1983 .- 0261-5614. ; 42:7, s. 1126-1141
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Diet and weight loss affect circulating metabolome. However, metabolite profiles induced by different weight loss maintenance diets and underlying longer term weight loss maintenance remain unknown. Herein, we investigated after-weight-loss metabolic signatures of two isocaloric 24-wk weight maintenance diets differing in satiety value due to dietary fibre, protein and fat contents and identified metabolite features that associated with successful weight loss maintenance. Methods: Non-targeted LC-MS metabolomics approach was used to analyse plasma metabolites of 79 women and men (mean age ± SD 49.7 ± 9.0 years; BMI 34.2 ± 2.5 kg/m2) participating in a weight management study. Participants underwent a 7-week very-low-energy diet (VLED) and were thereafter randomised into two groups for a 24-week weight maintenance phase. Higher satiety food (HSF) group consumed high-fibre, high-protein, and low-fat products, while lower satiety food (LSF) group consumed isocaloric low-fibre products with average protein and fat content as a part of their weight maintenance diets. Plasma metabolites were analysed before the VLED and before and after the weight maintenance phase. Metabolite features discriminating HSF and LSF groups were annotated. We also analysed metabolite features that discriminated participants who maintained ≥10% weight loss (HWM) and participants who maintained <10% weight loss (LWM) at the end of the study, irrespective of the diet. Finally, we assessed robust linear regression between metabolite features and anthropometric and food group variables. Results: We annotated 126 metabolites that discriminated the HSF and LSF groups and HWM and LWM groups (p < 0.05). Compared to LSF, the HSF group had lower levels of several amino acids, e.g. glutamine, arginine, and glycine, short-, medium- and long-chain acylcarnitines (CARs), odd- and even-chain lysoglycerophospholipids, and higher levels of fatty amides. Compared to LWM, the HWM group in general showed higher levels of glycerophospholipids with a saturated long-chain and a C20:4 fatty acid tail, and unsaturated free fatty acids (FFAs). Changes in several saturated odd- and even-chain LPCs and LPEs and fatty amides were associated with the intake of many food groups, particularly grain and dairy products. Increase in several (lyso)glycerophospholipids was associated with decrease in body weight and adiposity. Increased short- and medium-chain CARs were related to decreased body fat-free mass. Conclusions: Our results show that isocaloric weight maintenance diets differing in dietary fibre, protein, and fat content affected amino acid and lipid metabolism. Increased abundances of several phospholipid species and FFAs were related with greater weight loss maintenance. Our findings indicate common and distinct metabolites for weight and dietary related variables in the context of weight reduction and weight management. The study was registered in isrctn.org with identifier 67529475.
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| 25. |
- Pesu, Hannah, et al.
(författare)
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Correlates of Plasma Citrulline, a Potential Marker of Enterocyte Mass, among Children with Stunting: A Cross-Sectional Study in Uganda
- 2024
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Ingår i: Journal of Nutrition. - 1541-6100 .- 0022-3166. ; 154:2, s. 765-776
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Tidskriftsartikel (refereegranskat)abstract
- Background: Environmental enteric dysfunction (EED) is associated with stunting. Citrulline, produced in mature enterocytes, may be a valuable biomarker of small intestinal enterocyte mass in the context of EED. Objectives: We aimed to explore the correlates of plasma citrulline (p-cit) in children with stunting. Methods: In a cross-sectional study using baseline data from the community-based MAGNUS (milk affecting growth, cognition and the gut in child stunting) trial (ISRCTN13093195), we explored potential correlates of p-cit in Ugandan children with stunting aged 12–59 mo. Using linear regression in univariate and multivariate models, we explored associations with socioeconomics, diet, micronutrient status, and water, sanitation, and hygiene characteristics. The influence of covariates age, fasting, and systemic inflammation were also explored. Results: In 750 children, the mean ± standard deviation age was 32.0 ± 11.7 mo, and height-for-age z-score was –3.02 ± 0.74. P-cit, available for 730 children, differed according to time fasted and was 20.7 ± 8.9, 22.3 ± 10.6 and 24.2 ± 13.1 μmol/L if fasted <2, 2–5 and >5 h, respectively. Positive correlates of p-cit were age [0.07; 95% confidence interval (CI): 0.001, 0.15 μmol/L] and log10 serum insulin-like growth factor-1 (8.88; 95% CI: 5.09, 12.67 μmol/L). With adjustment for systemic inflammation, the association with serum insulin-like growth factor-1 reduced (4.98; 95% CI: 0.94, 9.03 μmol/L). Negative correlates of p-cit included food insecurity, wet season (–3.12; 95% CI: –4.97, –1.26 μmol/L), serum C-reactive protein (–0.15; 95% CI: –0.20, –0.10 μmol/L), serum α1-acid glycoprotein (–5.34; 95% CI: –6.98, –3.70 μmol/L) and anemia (–1.95; 95% CI: –3.72, –0.18 μmol/L). Among the negatively correlated water, sanitation, and hygiene characteristics was lack of soap for handwashing (–2.53; 95% CI: –4.82, –0.25 μmol/L). Many associations attenuated with adjustment for inflammation. Conclusions: Many of the correlates of p-cit are characteristic of populations with a high EED prevalence. Systemic inflammation is strongly associated with p-cit and is implicated in EED and stunting. Adjustment for systemic inflammation attenuates many associations, reflecting either confounding, mediation, or both. This study highlights the complex interplay between p-cit and systemic inflammation.
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| 26. |
- Reder, Gabriel, 1992, et al.
(författare)
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AutonoMS: Automated Ion Mobility Metabolomic Fingerprinting
- 2024
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Ingår i: Journal of the American Society for Mass Spectrometry. - 1044-0305 .- 1879-1123. ; 35:3, s. 542-550
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Tidskriftsartikel (refereegranskat)abstract
- Automation is dramatically changing the nature of laboratory life science. Robotic lab hardware that can perform manual operations with greater speed, endurance, and reproducibility opens an avenue for faster scientific discovery with less time spent on laborious repetitive tasks. A major bottleneck remains in integrating cutting-edge laboratory equipment into automated workflows, notably specialized analytical equipment, which is designed for human usage. Here we present AutonoMS, a platform for automatically running, processing, and analyzing high-throughput mass spectrometry experiments. AutonoMS is currently written around an ion mobility mass spectrometry (IM-MS) platform and can be adapted to additional analytical instruments and data processing flows. AutonoMS enables automated software agent-controlled end-to-end measurement and analysis runs from experimental specification files that can be produced by human users or upstream software processes. We demonstrate the use and abilities of AutonoMS in a high-throughput flow-injection ion mobility configuration with 5 s sample analysis time, processing robotically prepared chemical standards and cultured yeast samples in targeted and untargeted metabolomics applications. The platform exhibited consistency, reliability, and ease of use while eliminating the need for human intervention in the process of sample injection, data processing, and analysis. The platform paves the way toward a more fully automated mass spectrometry analysis and ultimately closed-loop laboratory workflows involving automated experimentation and analysis coupled to AI-driven experimentation utilizing cutting-edge analytical instrumentation. AutonoMS documentation is available at https://autonoms.readthedocs.io.
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| 27. |
- Repecka, Donatas, et al.
(författare)
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Expanding functional protein sequence spaces using generative adversarial networks
- 2021
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Ingår i: Nature Machine Intelligence. - : Springer Science and Business Media LLC. - 2522-5839. ; 3:4, s. 324-333
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Tidskriftsartikel (refereegranskat)abstract
- De novo protein design for catalysis of any desired chemical reaction is a long-standing goal in protein engineering because of the broad spectrum of technological, scientific and medical applications. However, mapping protein sequence to protein function is currently neither computationally nor experimentally tangible. Here, we develop ProteinGAN, a self-attention-based variant of the generative adversarial network that is able to ‘learn’ natural protein sequence diversity and enables the generation of functional protein sequences. ProteinGAN learns the evolutionary relationships of protein sequences directly from the complex multidimensional amino-acid sequence space and creates new, highly diverse sequence variants with natural-like physical properties. Using malate dehydrogenase (MDH) as a template enzyme, we show that 24% (13 out of 55 tested) of the ProteinGAN-generated and experimentally tested sequences are soluble and display MDH catalytic activity in the tested conditions in vitro, including a highly mutated variant of 106 amino-acid substitutions. ProteinGAN therefore demonstrates the potential of artificial intelligence to rapidly generate highly diverse functional proteins within the allowed biological constraints of the sequence space.
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| 28. |
- Ronkainen, Justiina, et al.
(författare)
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LongITools: Dynamic longitudinal exposome trajectories in cardiovascular and metabolic noncommunicable diseases
- 2022
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Ingår i: Environmental Epidemiology. - 2474-7882. ; 6:1
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Tidskriftsartikel (refereegranskat)abstract
- The current epidemics of cardiovascular and metabolic noncommunicable diseases have emerged alongside dramatic modifications in lifestyle and living environments. These correspond to changes in our "modern" postwar societies globally characterized by rural-to-urban migration, modernization of agricultural practices, and transportation, climate change, and aging. Evidence suggests that these changes are related to each other, although the social and biological mechanisms as well as their interactions have yet to be uncovered. LongITools, as one of the 9 projects included in the European Human Exposome Network, will tackle this environmental health equation linking multidimensional environmental exposures to the occurrence of cardiovascular and metabolic noncommunicable diseases.
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| 29. |
- Ross, Alastair, 1976, et al.
(författare)
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A high-throughput method for liquid chromatography-tandem mass spectrometry determination of plasma alkylresorcinols, biomarkers of whole grain wheat and rye intake.
- 2016
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 499, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- Plasma alkylresorcinols are increasingly analyzed in cohort studies to improve estimates of whole grain intake and their relationship with disease incidence. Current methods require large volumes of solvent (>10 ml/sample) and have relatively low daily sample throughput. We tested five different supported extraction methods for extracting alkylresorcinols from plasma and improved a normal-phase liquid chromatography coupled to a tandem mass spectrometer method to reduce sample analysis time. The method was validated and compared with gas chromatography-mass spectrometry analysis. Sample preparation with HybridSPE supported extraction was most effective for alkylresorcinol extraction, with recoveries of 77-82% from 100 μl of plasma. The use of 96-well plates allowed extraction of 160 samples per day. Using a 5-cm NH2 column and heptane reduced run times to 3 min. The new method had a limit of detection and limit of quantification equivalent to 1.1-1.8 nmol/L and 3.5-6.1 nmol/L plasma, respectively, for the different alkylresorcinol homologues. Accuracy was 93-105%, and intra- and inter-batch precision values were 4-18% across different plasma concentrations. This method makes it possible to quantify plasma alkylresorcinols in 100 μl of plasma at a rate of at least 160 samples per day without the need for large volumes of organic solvents.
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| 30. |
- Ross, Alastair, 1976, et al.
(författare)
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A new biomarker for quinoa intake
- 2014
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Ingår i: FASEB Journal. - 1530-6860 .- 0892-6638. ; 28:1
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 31. |
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| 32. |
- Ross, Alastair, 1976, et al.
(författare)
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Identification and quantification of even and odd chained 5-n alkylresorcinols, branched chain-alkylresorcinols and methylalkylresorcinols in Quinoa (Chenopodium quinoa)
- 2017
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Ingår i: Food Chemistry. - : Elsevier BV. - 0308-8146 .- 1873-7072. ; 220, s. 344-351
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Tidskriftsartikel (refereegranskat)abstract
- Quinoa is a pseudocereal grown in the Andean region of South America that is of increasing interest worldwide as an alternative staple food. We have detected a complex mixture of both odd- and even-alkyl chain alkylresorcinols (AR), branched-chain alkylresorcinols (bcAR) and methylalkylresorcinols (mAR) in ethyl acetate extracts of quinoa. We quantified the content of AR in 17 commercial samples of quinoa, and found that the mean±SD content of AR was 58±16μg/g, bcAR was 182±52μg/g, and mAR was 136±40μg/g. AR from quinoa could also be detected in plasma after eating quinoa, indicating that some of these unique AR could be used as biomarkers of quinoa intake in humans. Further work is required to understand the role of these ARs in the quinoa plant and whether any of the novel ARs may be of particular interest in human nutrition. © 2016 Elsevier Ltd
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| 33. |
- Ross, Alastair, 1976, et al.
(författare)
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Making complex measurements of meat composition fast: Application of rapid evaporative ionisation mass spectrometry to measuring meat quality and fraud
- 2021
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Ingår i: Meat Science. - : Elsevier BV. - 0309-1740. ; 181
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Tidskriftsartikel (refereegranskat)abstract
- Increasing demands are being placed on meat producers to verify more about their product with regards to safety, quality and authenticity. There are many methods that can detect aspects of these parameters in meat, yet most are too slow to keep up with the demands of modern meat processing plants and supply chains. A new technology, Rapid Evaporative Ionisation Mass Spectrometry (REIMS), has the potential to bridge the gap between advanced laboratory measurements and technology that can screen for quality, safety and authenticity parameters in a single measurement. Analysis with REIMS generates a detailed mass spectral fingerprint representative of a meat sample without the need for sample processing. REIMS has successfully been used to detect species fraud, detect use of hormones in meat animals, monitor meat processing and to detect off flavours such as boar taint. The aim of this review is to summarize these and other applications to highlight the potential of REIMS for meat analysis. Sampling methods and important considerations for data analysis are discussed as well as limitations of the technology and remaining challenges for practical adoption.
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| 34. |
- Ross, Alastair, 1976, et al.
(författare)
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Umbilical cord blood metabolome differs in relation to delivery mode, birth order and sex, maternal diet and possibly future allergy development in rural children
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Allergy is one of the most common diseases among young children yet all factors that affect development of allergy remain unclear. In a small cohort of 65 children living in the same rural area of south-west Sweden, we have previously found that maternal factors, including prenatal diet, affect childhood allergy risk, suggesting that in utero conditions may be important for allergy development. Here, we studied if metabolites in the umbilical cord blood of newborns may be related to development of childhood allergy, accounting for key perinatal factors such as mode of delivery, birth order and sex. Available umbilical cord blood plasma samples from 44 of the participants were analysed using gas chromatography-mass spectrometry metabolomics; allergy was diagnosed by specialised paediatricians at ages 18 months, 3 years and 8 years and included eczema, asthma, food allergy and allergic rhinoconjunctivitis. Nineteen cord blood metabolites were related to future allergy diagnosis though there was no clear pattern of up- or downregulation of metabolic pathways. In contrast, perinatal factors birth order, sex and mode of delivery affected several energy and biosynthetic pathways, including glutamate and aspartic acid-histidine metabolism (p = 0.004) and the tricarboxylic acid cycle (p = 0.006) for birth order; branched chain amino acid metabolism (p = 0.0009) and vitamin B-6 metabolism (p = 0.01) for sex; and glyoxylate and dicarboxylic acid metabolism (p = 0.005) for mode of delivery. Maternal diet was also related to some of the metabolites associated with allergy. In conclusion, the cord blood metabolome includes individual metabolites that reflect lifestyle, microbial and other factors that may be associated with future allergy diagnosis, and also reflects temporally close events/factors. Larger studies are required to confirm these associations, and perinatal factors such as birth order or siblings must be considered in future cord-blood metabolome studies.
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| 35. |
- Savolainen, Otto, 1982, et al.
(författare)
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A Simultaneous Metabolic Profiling and Quantitative Multimetabolite Metabolomic Method for Human Plasma Using Gas-Chromatography Tandem Mass Spectrometry.
- 2016
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3907 .- 1535-3893. ; 15:1, s. 259-265
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Tidskriftsartikel (refereegranskat)abstract
- For the first time it is possible to simultaneously collect targeted and nontargeted metabolomics data from plasma based on GC with high scan speed tandem mass spectrometry (GC-MS/MS). To address the challenge of getting broad metabolome coverage while quantifying known biomarker compounds in high-throughput GC-MS metabolomics, we developed a novel GC-MS/MS metabolomics method using a high scan speed (20 000 Da/second) GC-MS/MS that enables simultaneous data acquisition of both nontargeted full scan and targeted quantitative tandem mass spectrometry data. The combination of these two approaches has hitherto not been demonstrated in metabolomics. This method allows reproducible quantification of at least 37 metabolites using multiple reaction monitoring (MRM) and full mass spectral scan-based detection of 601 reproducible metabolic features from human plasma. The method showed good linearity over normal concentrations in plasma (0.06-343 to 0.86-4800 μM depending on the metabolite) and good intra- and interbatch precision (0.9-16.6 and 2.6-29.6% relative standard deviation). Based on the parameters determined for this method, targeted quantification using MRM can be expanded to cover at least 508 metabolites while still collecting full scan data. The new simultaneous targeted and nontargeted metabolomics method enables more sensitive and accurate detection of predetermined metabolites and biomarkers of interest, while still allowing detection and identification of unknown metabolites. This is the first validated GC-MS/MS metabolomics method with simultaneous full scan and MRM data collection, and clearly demonstrates the utility of GC-MS/MS with high scanning rates for complex analyses.
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| 36. |
- Savolainen, Otto, 1982, et al.
(författare)
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Biomarkers for predicting type 2 diabetes development-Can metabolomics improve on existing biomarkers?
- 2017
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:7
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Tidskriftsartikel (refereegranskat)abstract
- Aim The aim was to determine if metabolomics could be used to build a predictive model for type 2 diabetes (T2D) risk that would improve prediction of T2D over current risk markers. Gas chromatography-tandem mass spectrometry metabolomics was used in a nested casecontrol study based on a screening sample of 64-year-old Caucasian women (n = 629). Candidate metabolic markers of T2D were identified in plasma obtained at baseline and the power to predict diabetes was tested in 69 incident cases occurring during 5.5 years followup. The metabolomics results were used as a standalone prediction model and in combination with established T2D predictive biomarkers for building eight T2D prediction models that were compared with each other based on their sensitivity and selectivity for predicting T2D. Established markers of T2D (impaired fasting glucose, impaired glucose tolerance, insulin resistance (HOMA), smoking, serum adiponectin)) alone, and in combination with metabolomics had the largest areas under the curve (AUC) (0.794 (95% confidence interval [0.738-0.850]) and 0.808 [0.749-0.867] respectively), with the standalone metabolomics model based on nine fasting plasma markers having a lower predictive power (0.657 [0.577-0.736]). Prediction based on non-blood based measures was 0.638 [0.565-0.711]). Established measures of T2D risk remain the best predictor of T2D risk in this population. Additional markers detected using metabolomics are likely related to these measures as they did not enhance the overall prediction in a combined model.
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| 37. |
- Savolainen, Otto, 1982, et al.
(författare)
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Biomarkers of food intake and nutrient status are associated with glucose tolerance status and development of Type 2 diabetes
- 2017
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Ingår i: The FASEB Journal. ; 31:S1, s. 655.4-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND Diet is frequently associated with both the development and prevention of type 2 diabetes (T2D) but there are a lack of objective tools for assessing the causal relationships between diet and T2D. Biomarkers of dietary intake could help strengthen the link between a healthy diet and prevention of diabetes.OBJECTIVE The objective of this study was to explore how diet is related to glucose tolerance status (GTS) and future development of T2D irrespective of metabolic syndrome (MetS) risk factors, using dietary biomarkers as an objective measure of dietary intake unconfounded by recall and reporting bias.RESEARCH DESIGN AND METHODS Dietary biomarkers were measured in plasma from 64-year old women with different glucose tolerance classifications (normal glucose tolerance; NGT (n=190), impaired glucose tolerance; IGT (n=209), and diabetes (n=230)), randomly selected from the population register in Gothenburg, Sweden. The same subjects were followed up after 5 years to determine changes in glucose tolerance (NGT (n=167), IGT (n=174) and diabetes (n=159)). Analysis of covariance (ANCOVA) adjusted for significant measures of MetS was used to explore baseline data for associations between dietary biomarkers, GTS and new T2D cases at follow up (n=69).RESULTS After adjustment for MetS risk factors, alpha-tocopherol, alkylresorcinols C17 and C19 (markers of whole grain wheat and rye), b-alanine (meat), eicosapentaenoic acid (fish) and linoleic acid were associated with GTS and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) (fish) and alpha-tocopherol with future development of T2D.CONCLUSIONS Several dietary biomarkers were strongly associated with GTS irrespective of MetS factors, underlining the role of diet in development and prevention of T2D. The use of multiple dietary biomarkers can provide a link with diet that is unencumbered by recall bias normally associated with dietary studies and allows examination of the role of diet even when dietary information is not available.
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| 38. |
- Savolainen, Otto, 1982, et al.
(författare)
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Biomarkers of food intake and nutrient status are associated with glucose tolerance status and development of type 2 diabetes in older Swedish women
- 2017
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 106:5, s. 1302-1310
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Tidskriftsartikel (refereegranskat)abstract
- Background: Diet is frequently associated with both the development and prevention of type 2 diabetes (T2D), but there is a lack of objective tools for assessing the relation between diet and T2D. Biomarkers of dietary intake are unconfounded by recall and reporting bias, and using multiple dietary biomarkers could help strengthen the link between a healthy diet and the prevention of T2D. Objective: The objective of this study was to explore how diet is related to glucose tolerance status (GTS) and to future development of T2D irrespective of common T2D and cardiovascular disease risk factors by using multiple dietary biomarkers. Design: Dietary biomarkers were measured in plasma from 64-yold Swedish women with different GTS [normal glucose tolerance (NGT; n = 190), impaired glucose tolerance (IGT; n = 209), and diabetes (n = 230)]. The same subjects were followed up after 5 y to determine changes in glucose tolerance (n = 167 for NGT, n = 174 for IGT, and n = 159 for diabetes). ANCOVA and logistic regression were used to explore baseline data for associations between dietary biomarkers, GTS, and new T2D cases at follow-up (n = 69). Results: Of the 10 dietary biomarkers analyzed, beta-alanine (beef) (P-raw, 0.001), alkylresorcinols C17 and C19 (whole-grain wheat and rye) (P-raw = 0.003 and 0.011), eicosapentaenoic acid (fish) (P-raw = 0.041), 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) (fish) (P-raw = 0.002), linoleic acid (P-raw, 0.001), oleic acid (P-raw = 0.003), and alpha-tocopherol (margarine and vegetable oil) (P-raw, 0.001) were associated with GTS, and CMPF (fish) (OR: 0.72; 95% CI: 0.56, 0.93; P-raw = 0.013) and alpha-tocopherol (OR: 0.71; 95% CI: 0.51, 0.98; P-raw = 0.041) were inversely associated with future T2D development. Conclusions: Several circulating dietary biomarkers were strongly associated with GTS after correction for known T2D risk factors, underlining the role of diet in the development and prevention of T2D. To our knowledge, this study is the first to use multiple dietary biomarkers to investigate the link between diet and disease risk.
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| 39. |
- Savolainen, Otto, 1982
(författare)
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GC-MS based metabolomics – Development of a next generation GC-MS method and its application to nutrition and biomarker research
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Metabolomics, the measurement of a broad range of small molecules in a sample, is maturing as a field in analytical chemistry and becoming a standard research tool in biological sciences for helping to generate a wider understanding of the complex biological mechanisms behind, for example, development of disease and effects of diet on health. Metabolomics analysis is generally divided into either targeted or untargeted metabolomics. The former ‘targets’ a specific set of molecules, often quantitatively, while the latter aims to detect as many metabolites as possible in the sample. Both of these approaches have their advantages and disadvantages, and combining both into one single analytical method could allow the specificity, sensitivity, and quantitation of targeted metabolomics to be combined with the broad coverage and potential to find unknown compounds that are the key advantages of untargeted metabolomics. In this thesis, a novel gas chromatography triple quadrupole metabolomics (GC-MS) method that exploits fast data acquisition to simultaneously acquire both targeted quantitative data using multiple reaction and selected ion monitoring, and untargeted qualitative data using full spectrum scanning. The method was developed for human blood plasma and applied to two studies. The first was a crossover intervention study comparing metabolic effects of consumption of herring with chicken and pork in 15 adults. The second was a prospective cohort of 600 older Swedish women for discovering predictive biomarkers of development of type 2 diabetes (T2D) and for exploration of the associations between potential dietary and nutrient biomarkers and glucose tolerance status and development of T2D in the same cohort. The evaluated method parameters (linearity, limit of detection and quantification, precision, accuracy, number of spectral features) supports the approach of combining targeted quantitative and untargeted qualitative data acquisition as a way to improve GC-MS metabolomics. The method was successfully applied to the analysis of 1200 samples from 600 subjects, measured over 24 separate analytical batches with an average within batch metabolite variation of 10 %, based on control sample metabolites detected using multiple reaction monitoring. In the intervention study, the new metabolomics method detected 190 identified metabolites, of which 18 were altered when subjects ate herring instead of chicken and pork. These changes were mainly around the tricarboxylic acid and urea cycles, with an apparent differential effect related to arginine metabolism. This finding was supported by finding that circulating nitric oxide was higher in male subjects after the herring diet compared to the chicken and pork diets. In the cohort study, we established that the best predictive markers of T2D detected using metabolomics improved on or had similar prediction to established predictors of T2D. Using a combination of both the targeted and untargeted data, we were also able to detect 10 dietary and nutrient biomarkers, many of which were strongly associated with glucose tolerance status and development of T2D in this cohort. This is one of the first studies using multiple dietary and nutrient biomarkers that suggests a clear role of diet in prevention of T2D. This supports the current dietary guidelines for eating whole grains and fish for preventing T2D. In conclusion, the metabolomics method developed as part of this thesis detects a wide array of known biomarkers in blood plasma while still providing global untargeted information and having the possibility of expansion by addition of targeted molecules of interest. The method proved to be robust during the analysis of a moderately sized sample set, supporting its further use in observational cohorts. Results from the application of this metabolomics method further support the potential of metabolomics to add value to biological research by highlighting diverse outcome- metabolite relationships that may otherwise be overlooked.
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| 40. |
- Savolainen, Otto, 1982, et al.
(författare)
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Glycosylated Benzoxazinoids Are Degraded during Fermentation of Wheat Bran
- 2015
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Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 63:25, s. 5943-5949
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Tidskriftsartikel (refereegranskat)abstract
- Benzoxazinoids are plant secondary metabolites found in whole grain cereal foods including bread. They are bioavailable and metabolized in humans, and therefore their potential bioactivity is of interest. However, effects of food processing on their content and structure are not yet studied. This study reports effects of bioprocessing on wheat bran benzoxazinoid content. Benzoxazinoid glycosides were completely degraded during fermentation, whereas metabolites of benzoxazinoid aglycones were formed. Fermentation conditions did not affect the conversion process, as both yeast and yeast/lactic acid bacteria mediated fermentations had generally similar impacts. Likewise, enzymatic treatment of the bioprocess samples did not affect the conversion, suggesting that these compounds most likely are freely bioavailable from the grain matrix and not linked to the cell wall polymers. Additionally, the results show that benzoxazinoids undergo structural conversion during the fermentation process, resulting in several unknown compounds that contribute to the phytochemical intake and necessitate further analysis.
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| 41. |
- Savolainen, Otto, 1982, et al.
(författare)
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The role of oxygen in the liquid fermentation of wheat bran
- 2014
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Ingår i: Food Chemistry. - : Elsevier BV. - 0308-8146 .- 1873-7072. ; 153, s. 424-431
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Tidskriftsartikel (refereegranskat)abstract
- The extensive use of wheat bran as a food ingredient is limited due to its bitter taste and hard texture. To overcome these, some preprocessing methods, such as fermentation with yeast and lactic acid bacteria or enzymatic treatments have been proposed. The current work studied microbial communities, acidification, ethanol formation and metabolite profile of wheat bran fermented in either aerated or anaerobic conditions. In aerated conditions, yeasts grew better and the production of organic acids was smaller, and hence pH was higher. In anaerobic conditions, lactic acid bacteria and endogenous heterotrophic bacteria grew better. Aeration had a large effect on the sourdough metabolite profile, as analyzed by UPLC-qTOF-MS. Anaerobic conditions induced degradation of ferulic and caffeic acids, whereas the amount of sinapic acid increased. Aeration caused degradation of amino acids and hydroxycinnamic acid derivatives of polyamines. The results suggest that the control of oxygen could be used for tailoring the properties of bran sourdough. (C) 2013 Elsevier Ltd. All rights reserved.
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| 42. |
- Soni, Nikulkumar, 1984, et al.
(författare)
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Eicosapentaenoic and Docosahexaenoic Acid-Enriched High Fat Diet Delays Skeletal Muscle Degradation in Mice
- 2016
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 8:9, s. 543-
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Tidskriftsartikel (refereegranskat)abstract
- Low-grade chronic inflammatory conditions such as ageing, obesity and related metabolic disorders are associated with deterioration of skeletal muscle (SkM). Human studies have shown that marine fatty acids influence SkM function, though the underlying mechanisms of action are unknown. As a model of diet-induced obesity, we fed C57BL/6J mice either a high fat diet (HFD) with purified marine fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (HFD-ED), a HFD with corn oil, or normal mouse chow for 8 weeks; and used transcriptomics to identify the molecular effects of EPA and DHA on SkM. Consumption of ED-enriched HFD modulated SkM metabolism through increased gene expression of mitochondrial β-oxidation and slow-fiber type genes compared with HFD-corn oil fed mice. Furthermore, HFD-ED intake increased nuclear localization of nuclear factor of activated T-cells (Nfatc4) protein, which controls fiber-type composition. This data suggests a role for EPA and DHA in mitigating some of the molecular responses due to a HFD in SkM. Overall, the results suggest that increased consumption of the marine fatty acids EPA and DHA may aid in the prevention of molecular processes that lead to muscle deterioration commonly associated with obesity-induced low-grade inflammation.
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| 43. |
- Soni, Nikulkumar, 1984, et al.
(författare)
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Splenic Immune Response Is Down-Regulated in C57BL/6J Mice Fed Eicosapentaenoic Acid and Docosahexaenoic Acid Enriched High Fat Diet
- 2017
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 9:1, s. 50-
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Tidskriftsartikel (refereegranskat)abstract
- © 2017 by the authors; licensee MDPI, Basel, Switzerland. Dietary n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are associated with reduction of inflammation, although the mechanisms are poorly understood, especially how the spleen, as a secondary lymphoid organ, is involved. To investigate the effects of EPA and DHA on spleen gene expression, male C57BL/6J mice were fed high fat diets (HFD) differing in fatty acid composition, either based on corn oil (HFD-CO), or CO enriched with 2 g/100 g EPA and DHA (HFD-ED), for eight weeks. Spleen tissue was analyzed using transcriptomics and for fatty acids profiling. Biological processes (BPs) related to the immune response, including T-cell receptor signaling pathway, T-cell differentiation and co-stimulation, myeloid dendritic cell differentiation, antigen presentation and processing, and the toll like receptor pathway were downregulated by HFD-ED compared with control and HFD-CO. These findings were supported by the down-regulation of NF-κB in HFD-ED compared with HFD-CO fed mice. Lower phospholipid arachidonic acid levels in HFD-ED compared with HFD-CO, and control mice suggest attenuation of pathways via prostaglandins and leukotrienes. The HFD-ED also upregulated BPs related to erythropoiesis and hematopoiesis compared with control and HFD-CO fed mice. Our findings suggest that EPA and DHA down-regulate the splenic immune response induced by HFD-CO, supporting earlier work that the spleen is a target organ for the anti-inflammatory effects of these n-3 fatty acids.
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| 44. |
- Vendelbo Lind, Mads, 1988, et al.
(författare)
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The use of mass spectrometry for analysing metabolite biomarkers in epidemiology: methodological and statistical considerations for application to large numbers of biological samples
- 2016
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 1573-7284 .- 0393-2990. ; 31:8, s. 717-733
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Forskningsöversikt (refereegranskat)abstract
- Data quality is critical for epidemiology, and as scientific understanding expands, the range of data available for epidemiological studies and the types of tools used for measurement have also expanded. It is essential for the epidemiologist to have a grasp of the issues involved with different measurement tools. One tool that is increasingly being used for measuring biomarkers in epidemiological cohorts is mass spectrometry (MS), because of the high specificity and sensitivity of MS-based methods and the expanding range of biomarkers that can be measured. Further, the ability of MS to quantify many biomarkers simultaneously is advantageously compared to single biomarker methods. However, as with all methods used to measure biomarkers, there are a number of pitfalls to consider which may have an impact on results when used in epidemiology. In this review we discuss the use of MS for biomarker analyses, focusing on metabolites and their application and potential issues related to large-scale epidemiology studies, the use of MS "omics" approaches for biomarker discovery and how MS-based results can be used for increasing biological knowledge gained from epidemiological studies. Better understanding of the possibilities and possible problems related to MS-based measurements will help the epidemiologist in their discussions with analytical chemists and lead to the use of the most appropriate statistical tools for these data.
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| 45. |
- VINCENT, ANDREW, 1981, et al.
(författare)
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Herring and chicken/pork meals lead to differences in plasma levels of TCA intermediates and arginine metabolites in overweight and obese men and women
- 2017
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Ingår i: Molecular Nutrition & Food Research. - : Wiley. - 1613-4125 .- 1613-4133. ; 61:3
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Tidskriftsartikel (refereegranskat)abstract
- Scope: What effect does replacing chicken or pork with herring as the main dietary source of protein have on the human plasma metabolome? Method and results: A randomised crossover trial with 15 healthy obese men and women (age 24-70 years). Subjects were randomly assigned to four weeks of herring diet or a reference diet of chicken and lean pork, five meals per week, followed by a washout and the other intervention arm. Fasting blood serum metabolites were analysed at 0, 2 and 4 weeks for eleven subjects with available samples, using GC-MS based metabolomics. The herring diet decreased plasma citrate, fumarate, isocitrate, glycolate, oxalate, agmatine and methyhistidine and increased asparagine, ornithine, glutamine and the hexosamine glucosamine. Modelling found that the tricarboxylic acid cycle, glyoxylate, and arginine metabolism were affected by the intervention. The effect on arginine metabolism was supported by an increase in blood nitric oxide in males on the herring diet. Conclusion: The results suggest that eating herring instead of chicken and lean pork leads to important metabolic effects, particularly on energy and amino acid metabolism. Our findings support the hypothesis that there are metabolic effects of herring intake unrelated to the long chain n-3 polyunsaturated fatty acid content.
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