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| 2. |
- 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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| 3. |
- 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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| 4. |
- Maitre, Léa, et al.
(författare)
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State-of-the-art methods for exposure-health studies: Results from the exposome data challenge event
- 2022
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 168
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Tidskriftsartikel (refereegranskat)abstract
- The exposome recognizes that individuals are exposed simultaneously to a multitude of different environmental factors and takes a holistic approach to the discovery of etiological factors for disease. However, challenges arise when trying to quantify the health effects of complex exposure mixtures. Analytical challenges include dealing with high dimensionality, studying the combined effects of these exposures and their interactions, integrating causal pathways, and integrating high-throughput omics layers. To tackle these challenges, the Barcelona Institute for Global Health (ISGlobal) held a data challenge event open to researchers from all over the world and from all expertises. Analysts had a chance to compete and apply state-of-the-art methods on a common partially simulated exposome dataset (based on real case data from the HELIX project) with multiple correlated exposure variables (P > 100 exposure variables) arising from general and personal environments at different time points, biological molecular data (multi-omics: DNA methylation, gene expression, proteins, metabolomics) and multiple clinical phenotypes in 1301 mother–child pairs. Most of the methods presented included feature selection or feature reduction to deal with the high dimensionality of the exposome dataset. Several approaches explicitly searched for combined effects of exposures and/or their interactions using linear index models or response surface methods, including Bayesian methods. Other methods dealt with the multi-omics dataset in mediation analyses using multiple-step approaches. Here we discuss features of the statistical models used and provide the data and codes used, so that analysts have examples of implementation and can learn how to use these methods. Overall, the exposome data challenge presented a unique opportunity for researchers from different disciplines to create and share state-of-the-art analytical methods, setting a new standard for open science in the exposome and environmental health field.
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| 5. |
- Nordin, Elise, 1985, et al.
(författare)
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Fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), but not gluten, elicit modest symptoms of irritable bowel syndrome: a double-blind, placebo-controlled, randomized three-way crossover trial
- 2022
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 115:2, s. 344-352
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Tidskriftsartikel (refereegranskat)abstract
- Background: Irritable bowel syndrome (IBS) has been associated with diets rich in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs), and gluten. Most previous studies have been single-blind and have focused on the elimination of FODMAPs or provocation with single FODMAPs. The effect of gluten is unclear, large trials isolating the effect of gluten from that of FODMAPs are needed. Objectives: The aims of this study were to ensure high intakes of a wide range of FODMAPs, gluten, or placebo, and to evaluate the effects on IBS symptoms using the IBS-severity scoring system (IBS-SSS). Methods: The study was carried out with a double-blind, placebo-controlled, randomized 3-way crossover design in a clinical facility in Uppsala from September 2018 to June 2019. In all, 110 participants fulfilling the IBS Rome IV criteria, with moderate to severe IBS, were randomly assigned; 103 (90 female, 13 male) completed the trial. Throughout, IBS participants maintained a diet with minimal FODMAP content and no gluten. Participants were block-randomly assigned to 1-wk interventions with FODMAPs (50 g/d), gluten (17.3 g/d), or placebo, separated by 1-wk washout. All participants who completed ≥1 intervention were included in the intention-to-treat analysis. Results: In participants with IBS (n = 103), FODMAPs caused higher IBS-SSS scores (mean 240 [95% CI: 222, 257]) than placebo (198 [180, 215]; P = 0.00056) or gluten (208 [190, 226]; P = 0.013); no differences were found between the placebo and gluten groups (P = 1.0). There were large interindividual differences in IBS-SSS scores associated with treatment. No adverse events were reported. Conclusion: In participants with IBS, FODMAPs had a modest effect on typical IBS symptoms, whereas gluten had no effect. The large interindividual differences in responses to the interventions warrant further detailed studies to identify possible underlying causes and enable individual prediction of responses. This trial was registered at www.clinicaltrials.gov as NCT03653689.
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| 6. |
- Nordin, Elise, 1985, et al.
(författare)
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Modest Conformity Between Self-Reporting of Bristol Stool Form and Fecal Consistency Measured by Stool Water Content in Irritable Bowel Syndrome and a FODMAP and Gluten Trial
- 2022
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 1572-0241 .- 0002-9270. ; 117:10, s. 1668-1674
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Altered bowel habits constitute a criterion of irritable bowel syndrome (IBS), with the Bristol Stool Form Scale (BSFS) as the recommended tool for assessment of fecal consistency. However, BSFS is devoid of a comprehensive objective evaluation in subjects with IBS. Therefore, we aimed to evaluate the concordance between subjective reporting of BSFS and objective stool water content in subjects with IBS. Furthermore, we evaluated whether intake of fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) or gluten would affect stool water content. METHODS: Data from a previous crossover trial in IBS with 1-week provocations of FODMAPs, gluten, or placebo were subanalyzed. After each intervention, fecal consistency was subjectively assessed using the BSFS and stool samples were collected. The stool water content was analyzed, where ≤68.5% water content was classified as hard stool, while ≥78% was classified as diarrhea. RESULTS: BSFS correlated to stool water content ( r = 0.36, P < 0.0001). The BSFS score increased in parallel with increasing water content, but with considerable overlap between BSFS scores. Stool water content differed between the BSFS categories 1-2, 3-5, and 6-7 (hard, normal, and loose, respectively) ( P < 0.0001). For BSFS categories 1-2, 77% had water content ≤68.5%, whereas for BSFS categories 6-7, 52% had water content ≥78%. There was no difference in stool water content after consumption of FODMAPs, gluten, or placebo ( P = 0.94). DISCUSSION: Subjective reporting of BSFS conforms only modestly with stool water content in IBS, warranting caution when subtyping IBS according to the BSFS. High intake of FODMAPs and gluten does not affect stool water content.
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| 7. |
- Pirttilä, Kristian, et al.
(författare)
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Comprehensive Peak Characterization (CPC) in Untargeted LC–MS Analysis
- 2022
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989 .- 2218-1989. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- LC–MS-based untargeted metabolomics is heavily dependent on algorithms for automated peak detection and data preprocessing due to the complexity and size of the raw data generated. These algorithms are generally designed to be as inclusive as possible in order to minimize the number of missed peaks. This is known to result in an abundance of false positive peaks that further complicate downstream data processing and analysis. As a consequence, considerable effort is spent identifying features of interest that might represent peak detection artifacts. Here, we present the CPC algorithm, which allows automated characterization of detected peaks with subsequent filtering of low quality peaks using quality criteria familiar to analytical chemists. We provide a thorough description of the methods in addition to applying the algorithms to authentic metabolomics data. In the example presented, the algorithm removed about 35% of the peaks detected by XCMS, a majority of which exhibited a low signal-to-noise ratio. The algorithm is made available as an R-package and can be fully integrated into a standard XCMS workflow.
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| 8. |
- 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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| 9. |
- Skantze, Viktor, 1992, et al.
(författare)
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Identifying metabotypes from tensor data
- 2022
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Metabolic response to diet shows large individual variation, which warrants tailored dietary recommendation i.e., personalized nutrition (PN). A step towards PN is to tailor diet to groups of individuals with similar metabolic phenotype, so called metabotypes (i.e., clusters of individuals with similar metabolism). Metabotyping of high-dimensional data is commonly performed in matrix form using matrix decompositions (e.g., PCA). However, data from e.g., crossover studies can be conveniently organized in multi-dimensional form (i.e., as tensor data) and methods for detecting metabotypes in such data are still lacking. We therefore aimed to develop and evaluate tools to identify potential metabotypes in high-dimensional tensor data. We developed two methods: The first uses CANDECOMP/PARAFAC (CP) decomposition directly on tensor data where clustering was performed on individual’s scores, whereas the second was developed specifically for time-resolved data and uses dynamic mode decomposition (DMD) to model metabolite dynamics, where clustering was performed on individual’s dynamic state trajectories. We applied the methods to identify metabotypes in data from a crossover acute post-prandial dietary intervention study on 17 overweight males (BMI 25–30 kg/m2, 41–67 y of age) undergoing three dietary interventions (pickled herring, baked herring and baked beef, measuring 79 metabolites (from GC-MS metabolomics) at 8 time points (0-7h). Both methods identified two potential metabotype clusters, predominantly in amino acids after the meat diet. The clustering associated to baseline levels of creatinine, strengthening the plausibility of found metabotypes. The CP method is a general approach, not specific to time-resolved data, and provides better fit if the data is multilinear. Conversely, DMD is designed for time-resolved data, for which it often provides a better fit than CP. We concluded that both the CP and the DMD approach are well suited to identify metabotypes in tensor data from a wide variety of complex experimental designs.
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