1. |
- Brunius, Carl, 1974, et al.
(författare)
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Prediction and modeling of pre-analytical sampling errors as a strategy to improve plasma NMR metabolomics data
- 2017
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1460-2059 .- 1367-4811. ; 33:22, s. 3567-3574
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Tidskriftsartikel (refereegranskat)abstract
- Biobanks are important infrastructures for life science research. Optimal sample handling regarding e.g. collection and processing of biological samples is highly complex, with many variables that could alter sample integrity and even more complex when considering multiple study centers or using legacy samples with limited documentation on sample management. Novel means to understand and take into account such variability would enable high-quality research on archived samples. This study investigated whether pre-analytical sample variability could be predicted and reduced by modeling alterations in the plasma metabolome, measured by NMR, as a function of pre-centrifugation conditions (1-36 h pre-centrifugation delay time at 4 A degrees C and 22 A degrees C) in 16 individuals. Pre-centrifugation temperature and delay times were predicted using random forest modeling and performance was validated on independent samples. Alterations in the metabolome were modeled at each temperature using a cluster-based approach, revealing reproducible effects of delay time on energy metabolism intermediates at both temperatures, but more pronounced at 22 A degrees C. Moreover, pre-centrifugation delay at 4 A degrees C resulted in large, specific variability at 3 h, predominantly of lipids. Pre-analytical sample handling error correction resulted in significant improvement of data quality, particularly at 22 A degrees C. This approach offers the possibility to predict pre-centrifugation delay temperature and time in biobanked samples before use in costly downstream applications. Moreover, the results suggest potential to decrease the impact of undesired, delay-induced variability. However, these findings need to be validated in multiple, large sample sets and with analytical techniques covering a wider range of the metabolome, such as LC-MS.
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2. |
- Enlund, Karolina Brunius, et al.
(författare)
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Dental home care in dogs-a questionnaire study among Swedish dog owners, veterinarians and veterinary nurses
- 2020
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Ingår i: BMC Veterinary Research. - : Springer Science and Business Media LLC. - 1746-6148. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Periodontal disease remains one of the dog's most common health issues, even though it is largely preventable by tooth brushing. Implementation of daily tooth brushing would not only improve animal welfare, but also reduce veterinary costs for the owner. There is a paucity of studies investigating attitudes, opinions and practices of dog owners, veterinarians, and veterinary nurses regarding preventative dental home care in dogs. The objective of this study was to investigate these parameters in Sweden, thereby providing a basis for improved prophylactic strategies. Methods Validated questionnaire surveys were distributed to all Swedish dog owners (n = 209,263), veterinarians (n = 3657) and veterinary nurses (n = 1650) with e-mail addresses in the national registry. The response rates were 32% for dog owners and veterinarians, and 38% for veterinary nurses. The survey questions concerned attitudes, opinions and practices regarding dental home care, including whether dog owners received information concerning dental home care or not, and if this information resulted in implementation. Results Attitudes, opinions and practices regarding dental home care are presented for Swedish dog owners, veterinarians, and veterinary nurses. A fundamental finding was that the absolute majority of Swedish dog owners do not perform adequate prophylactic dental home care. Considerable discrepancies were identified in the opinions of veterinary health practitioners and dog owners regarding attitudes towards dental home care and conveying of information. Several areas for improvement in the communication between dog owners and veterinary health practitioners concerning dental home care were identified. Conclusion Our results illustrates the need for validated methods to increase dog owner compliance with dental home care recommendations. We also see a need of further education, regarding canine dental home care, among veterinarians, veterinary nurses, and dog owners. The results from this unique study constitute an important foundation for future development of prophylactic strategies, with the ultimate goal to improve dental health, and thereby animal welfare, in dogs.
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3. |
- Enlund, Karolina Brunius, et al.
(författare)
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Development and validation of two questionnaires: Dental home care and dental health in Swedish dogs
- 2019
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: Dental disease is one of the most common health problems in dogs. However, no studies have investigated the attitudes, opinions and practices of dog owners, veterinarians and veterinary nurses regarding dental health and preventative dental home care in dogs. The objective of this study was therefore to develop and validate questionnaires for this purpose, in accordance with survey methodology guidelines. Methods: Questionnaire items were determined based on the authors' academic knowledge and clinical experience, and modified throughout the validation process. Several measures were taken to reduce sampling, coverage, measurement and non-response errors. Content validity was assessed by Subject-Matter Experts (SME) and cognitive interviews were conducted in accordance with the “think-aloud protocol”. Non-response analysis was performed using several methods. Results: Constructs were identified using exploratory factor analysis and two predefined constructs from the dog owner questionnaire were confirmed “Dog owners' attitudes towards brushing their dog's teeth” (Cronbach's α = 0.86) and “Dog owners' assessment of their dog's dental health” (α = 0.76). Additionally, exploratory factor analysis identified three potential constructs. In the veterinary health practitioner questionnaire, two constructs were identified: “Veterinary health practitioners' attitudes towards dental chews and dental feed” (α = 0.78) and “Veterinary health practitioners' attitudes and opinions on dental problems and dental cleaning” (α = 0.73). Non-response analysis showed a higher proportion of women in the sample of dog owners and veterinarians compared to the target populations. Veterinarians in the sample were also younger. In contrast, gender and age distributions in veterinary nurses did not differ between sample and target. Conclusion: The validation presented in this work showed that the developed questionnaires could be used as accurate and reliable tools for measuring attitudes and practices regarding dental home care in dogs among Swedish dog owners, veterinarians and veterinary nurses.
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4. |
- Enlund, Karolina Brunius, et al.
(författare)
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Dog Owners' Perspectives on Canine Dental Health : A Questionnaire Study in Sweden
- 2020
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Ingår i: Frontiers in Veterinary Science. - : Frontiers Media SA. - 2297-1769. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Periodontal disease is one of the most common diseases affecting dogs, with a reported prevalence of at least 80% in dogs over 3 years of age. However, there is a lack of studies regarding dog owners' assessment of their dog's dental health, and whether they perceive clinical signs often associated with periodontal disease, i.e., dental calculus, halitosis or mobile or lost teeth. A validated questionnaire survey was distributed to all Swedish dog owners with email addresses in the national registry (n = 209,263). The response rate was 32%. The survey questions concerned opinions and practices regarding canine dental health, including assessment of dental health parameters and dog owners' ability to examine their dog's mouth. A construct (α = 0.76) was used to investigate dog owners' assessed symptoms of their dog's dental health in relation to background factors. Half of the respondents rated their dog's dental health as very good. However, one in four dog owners experienced difficulties when inspecting the dog's teeth. The most common reason for this difficulty was stated to be an uncooperative dog. Almost half of the dog owners reported halitosis to some degree in their dog, and almost four in ten owners reported dental calculus. One in eight dogs had been previously anesthetized for dental cleaning, and one in 12 dogs had experienced problems with gum disease, according to the owners. Owners' assessment varied significantly with the dog's age, weight, breed, breed group, sex, and concurrent disease. Owner-related factors that influenced the assessment of the dog's dental health were age, gender, education, county (urban/rural), and whether they were breeders or not. Dog owners with smaller dogs, older dogs and certain breeds predisposed to periodontal disease assessed their dog's dental health as worse than their counterparts, which is in agreement with previously reported higher prevalence of dental disease in these groups. This indicates that dog owners are able to perform relative assessment of their dog's dental health status. Our results also highlight the need for routine professional assessment of periodontal health, as well as education of dog owners and training of dogs to accept dental care procedures.
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5. |
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6. |
- Enlund, Karolina Brunius, et al.
(författare)
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Professional dental cleaning in dogs: clinical routines among Swedish veterinarians and veterinary nurses
- 2020
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Ingår i: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 1751-0147 .- 0044-605X. ; 62:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dental disease is very common in dogs and veterinary professional dental cleaning and examination, together with daily dental home care, is the foundation for good dental health. To our knowledge, no previous study has investigated professional dental cleaning routines in small animal veterinary practice. A validated questionnaire survey was distributed to all veterinarians and veterinary nurses with registered e-mail addresses in the Swedish national registry (veterinarians; n = 3657, veterinary nurses; n = 1650). Response rates were 32% for veterinarians (V) and 38% for veterinary nurses (VN). Results: In total, 73% (V)/96% (VN) of respondents reported that professional dental cleaning was performed at their work place under general anesthesia, and 27% (V)/18% (VN) that dental cleaning was performed under sedation. Of the respondents, 43% (V)/96% (VN) considered regular dental cleaning under general anesthesia fairly or very important, and 49% (V)/47% (VN) stated that it was sometimes important for good dental health in dogs. A majority of respondents, 84% (V)/97% (VN), reported that dental extractions were performed at their clinic, and 72% (V)/90% (VN) had access to dental radiography equipment. Conclusion: A majority of Swedish veterinarians and veterinary nurses perform professional dental cleaning under general anesthesia with access to dental radiography equipment, in accordance with national and international recommendations. However, a considerable proportion of professional dental cleanings were performed under sedation only, and extractions performed without access to dental radiography equipment were common, suggesting several areas of improvement in the routines in Swedish veterinary clinics and hospitals. Our results clearly indicate the need for improved educational efforts to increase the awareness among veterinary health professionals regarding guidelines and official recommendations in canine dental care.
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7. |
- Rådjursöga, Millie, 1977, et al.
(författare)
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The H-1 NMR serum metabolomics response to a two meal challenge: a cross-over dietary intervention study in healthy human volunteers
- 2019
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Ingår i: Nutrition Journal. - : Springer Science and Business Media LLC. - 1475-2891. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Metabolomics represents a powerful tool for exploring modulation of the human metabolome in response to food intake. However, the choice of multivariate statistical approach is not always evident, especially for complex experimental designs with repeated measurements per individual. Here we have investigated the serum metabolic responses to two breakfast meals: an egg and ham based breakfast and a cereal based breakfast using three different multivariate approaches based on the Projections to Latent Structures framework. Methods: In a cross over design, 24 healthy volunteers ate the egg and ham breakfast and cereal breakfast on four occasions each. Postprandial serum samples were subjected to metabolite profiling using H-1 nuclear magnetic resonance spectroscopy and metabolites were identified using 2D nuclear magnetic resonance spectroscopy. Metabolic profiles were analyzed using Orthogonal Projections to Latent Structures with Discriminant Analysis and Effect Projections and ANOVA-decomposed Projections to Latent Structures. Results: The Orthogonal Projections to Latent Structures with Discriminant Analysis model correctly classified 92 and 90% of the samples from the cereal breakfast and egg and ham breakfast, respectively, but confounded dietary effects with inter-personal variability. Orthogonal Projections to Latent Structures with Effect Projections removed inter-personal variability and performed perfect classification between breakfasts, however at the expense of comparing means of respective breakfasts instead of all samples. ANOVA-decomposed Projections to Latent Structures managed to remove inter-personal variability and predicted 99% of all individual samples correctly. Proline, tyrosine, and N-acetylated amino acids were found in higher concentration after consumption of the cereal breakfast while creatine, methanol, and isoleucine were found in higher concentration after the egg and ham breakfast. Conclusions: Our results demonstrate that the choice of statistical method will influence the results and adequate methods need to be employed to manage sample dependency and repeated measurements in cross-over studies. In addition, H-1 nuclear magnetic resonance serum metabolomics could reproducibly characterize postprandial metabolic profiles and identify discriminatory metabolites largely reflecting dietary composition.
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8. |
- Almanza-Aguilera, Enrique, et al.
(författare)
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Impact in Plasma Metabolome as Effect of Lifestyle Intervention for Weight-Loss Reveals Metabolic Benefits in Metabolically Healthy Obese Women
- 2018
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3907 .- 1535-3893. ; 17:8, s. 2600-2610
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Tidskriftsartikel (refereegranskat)abstract
- Little is known regarding metabolic benefits of weight loss (WL) on the metabolically healthy obese (MHO) patients. We aimed to examine the impact of a lifestyle weight loss (LWL) treatment on the plasma metabolomic profile in MHO individuals. Plasma samples from 57 MHO women allocated to an intensive LWL treatment group (TG, hypocaloric Mediterranean diet and regular physical activity, n = 30) or to a control group (CG, general recommendations of a healthy diet and physical activity, n = 27) were analyzed using an untargeted1H NMR metabolomics approach at baseline, after 3 months (intervention), and 12 months (follow-up). The impact of the LWL intervention on plasma metabolome was statistically significant at 3 months but not at follow-up and included higher levels of formate and phosphocreatine and lower levels of LDL/VLDL (signals) and trimethylamine in the TG. These metabolites were also correlated with WL. Higher myo-inositol, methylguanidine, and 3-hydroxybutyrate, and lower proline, were also found in the TG; higher levels of hippurate and asparagine, and lower levels of 2-hydroxybutyrate and creatine, were associated with WL. The current findings suggest that an intensive LWL treatment, and the consequent WL, leads to an improved plasma metabolic profile in MHO women through its impact on energy, amino acid, lipoprotein, and microbial metabolism.
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9. |
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10. |
- Bodén, Stina, et al.
(författare)
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Dietary patterns, untargeted metabolite profiles and their association with colorectal cancer risk
- 2024
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322 .- 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- We investigated data-driven and hypothesis-driven dietary patterns and their association to plasma metabolite profiles and subsequent colorectal cancer (CRC) risk in 680 CRC cases and individually matched controls. Dietary patterns were identified from combined exploratory/confirmatory factor analysis. We assessed association to LC–MS metabolic profiles by random forest regression and to CRC risk by multivariable conditional logistic regression. Principal component analysis was used on metabolite features selected to reflect dietary exposures. Component scores were associated to CRC risk and dietary exposures using partial Spearman correlation. We identified 12 data-driven dietary patterns, of which a breakfast food pattern showed an inverse association with CRC risk (OR per standard deviation increase 0.89, 95% CI 0.80–1.00, p = 0.04). This pattern was also inversely associated with risk of distal colon cancer (0.75, 0.61–0.96, p = 0.01) and was more pronounced in women (0.69, 0.49–0.96, p = 0.03). Associations between meat, fast-food, fruit soup/rice patterns and CRC risk were modified by tumor location in women. Alcohol as well as fruit and vegetables associated with metabolite profiles (Q2 0.22 and 0.26, respectively). One metabolite reflecting alcohol intake associated with increased CRC risk, whereas three metabolites reflecting fiber, wholegrain, and fruit and vegetables associated with decreased CRC risk.
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11. |
- Brunius, Carl, 1974, et al.
(författare)
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Targeted and untargeted metabolomics for specific food intake assessment whole grains as an example
- 2017
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Ingår i: Advances in the Assessment of Dietary Intake. - Boca Raton : CRC Press, 2017. : CRC Press. - 9781498749329 ; , s. 315-336
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This chapter provides an overview of the current available knowledge about alternative approaches to address food intakes by using dietary biomarkers. Biomarkers of whole grain intake identified by targeted and untargeted metabolomics approaches will be used as illustrative examples. The chapter addresses discovery, validation, and implementation of biomarkers of specific foods using targeted, and with particular emphasis, untargeted metabolomics approaches with whole grain foods as an example of a food category important to human health. The choice of experimental design for biomarker discovery will have a large impact on the choice of statistical techniques, what can be found in the data, and also on workload of study participants and researchers. The gold standard for statistical modeling validation is to use external validation, i.e. that separate datasets are used for model construction and validation. The chapter outlines a suggested approach to discover urinary biomarkers of specific food consumption using whole grain rye consumption in a healthy, free-living population as an example.
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12. |
- Cheng, Ken, 1987, et al.
(författare)
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An LC-QToF MS based method for untargeted metabolomics of human fecal samples
- 2020
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Ingår i: Metabolomics. - : Springer Science and Business Media LLC. - 1573-3882 .- 1573-3890. ; 16:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Consensus in sample preparation for untargeted human fecal metabolomics is lacking. Objectives: To obtain sample preparation with broad metabolite coverage for high-throughput LC–MS. Methods: Extraction solvent, solvent ratio and fresh frozen-vs-lyophilized samples were evaluated by metabolite feature quality. Results: Methanol at 5 mL per g wet feces provided a wide metabolite coverage with optimal balance between signal intensity and saturation for both fresh frozen and lyophilized samples. Lyophilization did not affect SCFA and is recommended because of convenience in normalizing to dry matter. Conclusion: The suggested sample preparation is simple, efficient and suitable for large-scale human fecal metabolomics.
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13. |
- Eriksen, Anne Kirstine, et al.
(författare)
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Effects of whole-grain wheat, rye, and lignan supplementation on cardiometabolic risk factors in men with metabolic syndrome: A randomized crossover trial
- 2020
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 111:4, s. 864-876
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Tidskriftsartikel (refereegranskat)abstract
- A whole-grain (WG)-rich diet has shown to have potential for both prevention and treatment of the metabolic syndrome (MetS), which is a cluster of risk factors that increase the risk of type 2 diabetes and cardiovascular disease. Different WGs may have different health effects. WG rye, in particular, may improve glucose homeostasis and blood lipids, possibly mediated through fermentable dietary fiber and lignans. Recent studies have also suggested a crucial role of the gut microbiota in response to WG. Objectives: The aim was to investigate WG rye, alone and with lignan supplements [secoisolariciresinol diglucoside (SDG)], and WG wheat diets on glucose tolerance [oral-glucose-tolerance test (OGTT)], other cardiometabolic outcomes, enterolignans, and microbiota composition. Moreover, we exploratively evaluated the role of gut microbiota enterotypes in response to intervention diets. Methods: Forty men with MetS risk profile were randomly assigned to WG diets in an 8-wk crossover study. The rye diet was supplemented with 280 mg SDG at weeks 4-8. Effects of treatment were evaluated by mixed-effects modeling, and effects on microbiota composition and the role of gut microbiota as a predictor of response to treatment were analyzed by random forest plots. Results: The WG rye diet (± SDG supplements) did not affect the OGTT compared with WG wheat. Total and LDL cholesterol were lowered (-0.06 and -0.09 mmol/L, respectively; P < 0.05) after WG rye compared with WG wheat after 4 wk but not after 8 wk. WG rye resulted in higher abundance of Bifidobacterium [fold-change (FC) = 2.58, P < 0.001] compared with baseline and lower abundance of Clostridium genus compared with WG wheat (FC = 0.54, P = 0.02). The explorative analyses suggest that baseline enterotype is associated with total and LDL-cholesterol response to diet. Conclusions: WG rye, alone or with SDG supplementation, compared with WG wheat did not affect glucose metabolism but caused transient LDL-cholesterol reduction. The effect of WG diets appeared to differ according to enterotype. This trial was registered at www.clinicaltrials.gov as NCT02987595.
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14. |
- Esberg, Anders, et al.
(författare)
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Carbonic Anhydrase 6 Gene Variation influences Oral Microbiota Composition and Caries Risk in Swedish adolescents
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- Carbonic anhydrase VI (CA6) catalyses the reversible hydration of carbon dioxide in saliva with possible pH regulation, taste perception, and tooth formation effects. This study assessed effects of variation in the CA6 gene on oral microbiota and specifically the acidophilic and caries-associated Streptococcus mutans in 17-year old Swedish adolescents (n = 154). Associations with caries status and secreted CA6 protein were also evaluated. Single Nucleotide Polymorphisms (27 SNPs in 5 haploblocks) and saliva and tooth biofilm microbiota from Illumina MiSeq 16S rDNA (V3-V4) sequencing and culturing were analysed. Haploblock 4 (rs10864376, rs3737665, rs12138897) CCC associated with low prevalence of S. mutans (OR (95% CI): 0.5 (0.3, 0.8)), and caries (OR 0.6 (0.3, 0.9)), whereas haploblock 4 TTG associated with high prevalence of S. mutans (OR: 2.7 (1.2, 5.9)) and caries (OR: 2.3 (1.2, 4.4)). The TTG-haploblock 4 (represented by rs12138897(G)) was characterized by S. mutans, Scardovia wiggsiae, Treponema sp. HOT268, Tannerella sp. HOT286, Veillonella gp.1 compared with the CCC-haploblock 4 (represented by rs12138897(C)). Secreted CA6 in saliva was weakly linked to CA6 gene variation. In conclusion, the results indicate that CA6 gene polymorphisms influence S. mutans colonization, tooth biofilm microbiota composition and risk of dental caries in Swedish adolescents.
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15. |
- Fernández-Ochoa, Álvaro, et al.
(författare)
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A case report of switching from specific vendor-based to R-based pipelines for untargeted LC-MS metabolomics
- 2020
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989 .- 2218-1989. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Data pre-processing of the LC-MS data is a critical step in untargeted metabolomics studies in order to achieve correct biological interpretations. Several tools have been developed for pre-processing, and these can be classified into either commercial or open source software. This case report aims to compare two specific methodologies, Agilent Profinder vs. R pipeline, for a metabolomic study with a large number of samples. Specifically, 369 plasma samples were analyzed by HPLC-ESI-QTOF-MS. The collected data were pre-processed by both methodologies and later evaluated by several parameters (number of peaks, degree of missingness, quality of the peaks, degree of misalignments, and robustness in multivariate models). The vendor software was characterized by ease of use, friendly interface and good quality of the graphs. The open source methodology could more effectively correct the drifts due to between and within batch effects. In addition, the evaluated statistical methods achieved better classification results with higher parsimony for the open source methodology, indicating higher data quality. Although both methodologies have strengths and weaknesses, the open source methodology seems to be more appropriate for studies with a large number of samples mainly due to its higher capacity and versatility that allows combining different packages, functions, and methods in a single environment.
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16. |
- Fernandez-Ochoa, Alvaro, et al.
(författare)
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Metabolic Disturbances in Urinary and Plasma Samples from Seven Different Systemic Autoimmune Diseases Detected by HPLC-ESI-QTOF-MS
- 2020
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3907 .- 1535-3893. ; 19:8, s. 3220-3229
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Tidskriftsartikel (refereegranskat)abstract
- Systemic autoimmune diseases (SADs) are characterized by dysfunctioning of the immune system, which causes damage in several tissues and organs. Among these pathologies are systemic lupus erythematosus (SLE), systemic sclerosis or scleroderma, Sjogren's syndrome, rheumatoid arthritis, primary antiphospholipid syndrome (PAPS), mixed connective tissue disease (MCTD), and undifferentiated connective tissue disease (UCTD). Early diagnosis is difficult due to similarity in symptoms, signs, and clinical test results. Hence, our aim was to search for differentiating metabolites of these diseases in plasma and urine samples. We performed metabolomic profiling by liquid chromatography-mass spectrometry (LC-MS) of samples from 228 SADs patients and 55 healthy volunteers. Multivariate PLS models were applied to investigate classification accuracies and identify metabolites differentiating SADs and healthy controls. Furthermore, we specifically investigated UCTD against the other SADs. PLS models were able to classify most SADs vs healthy controls (area under the roc curve (AUC) > 0.7), with the exception of MCTD and PAPS. Differentiating metabolites consisted predominantly of unsaturated fatty acids, acylglycines, acylcarnitines, and amino acids. In accordance with the difficulties in defining UCTD, the UCTD metabolome did not differentiate well from the other SADs. However, most UCTD cases were dassified as SLE, suggesting that metabolomics may provide a tool to reassess UCTD diagnosis into other conditions for more well-informed therapeutic strategies.
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17. |
- González-Domínguez, Álvaro, et al.
(författare)
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QComics: Recommendations and Guidelines for Robust, Easily Implementable and Reportable Quality Control of Metabolomics Data
- 2024
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Ingår i: Analytical Chemistry. - 0003-2700 .- 1520-6882. ; 96:3, s. 1064-1072
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Tidskriftsartikel (refereegranskat)abstract
- The implementation of quality control strategies is crucial to ensure the reproducibility, accuracy, and meaningfulness of metabolomics data. However, this pivotal step is often overlooked within the metabolomics workflow and frequently relies on the use of nonstandardized and poorly reported protocols. To address current limitations in this respect, we have developed QComics, a robust, easily implementable and reportable method for monitoring and controlling data quality. The protocol operates in various sequential steps aimed to (i) correct for background noise and carryover, (ii) detect signal drifts and “out-of-control” observations, (iii) deal with missing data, (iv) remove outliers, (v) monitor quality markers to identify samples affected by improper collection, preprocessing, or storage, and (vi) assess overall data quality in terms of precision and accuracy. Notably, this tool considers important issues often neglected along quality control, such as the need of separately handling missing values and truly absent data to avoid losing relevant biological information, as well as the large impact that preanalytical factors may elicit on metabolomics results. Altogether, the guidelines compiled in QComics might contribute to establishing gold standard recommendations and best practices for quality control within the metabolomics community.
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18. |
- 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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20. |
- Harlid, Sophia, 1978-, et al.
(författare)
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A two-tiered targeted proteomics approach to identify pre-diagnostic biomarkers of colorectal cancer risk
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer prognosis is dependent on stage, and measures to improve early detection are urgently needed. Using prospectively collected plasma samples from the population-based Northern Sweden Health and Disease Study, we evaluated protein biomarkers in relation to colorectal cancer risk. Applying a two-tiered approach, we analyzed 160 proteins in matched sequential samples from 58 incident colorectal cancer case–control pairs. Twenty-one proteins selected from both this discovery phase and the literature were then analyzed in a validation set of 450 case–control pairs. Odds ratios were estimated by conditional logistic regression. LASSO regression and ROC analysis were used for multi-marker analyses. In the main validation analysis, no proteins retained statistical significance. However, exploratory subgroup analyses showed associations between FGF-21 and colon cancer risk (multivariable OR per 1 SD: 1.23 95% CI 1.03–1.47) as well as between PPY and rectal cancer risk (multivariable OR per 1 SD: 1.47 95% CI 1.12–1.92). Adding protein markers to basic risk predictive models increased performance modestly. Our results highlight the challenge of developing biomarkers that are effective in the asymptomatic, prediagnostic window of opportunity for early detection of colorectal cancer. Distinguishing between cancer subtypes may improve prediction accuracy. However, single biomarkers or small panels may not be sufficient for effective precision screening.
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21. |
- Hartvigsson, Olle, 1991, et al.
(författare)
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Associations of maternal and infant metabolomes with immune maturation and allergy development at 12 months in the Swedish NICE-cohort
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322 .- 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Allergic diseases are the most common chronic diseases in childrenin the Western world, but little is know about what factors influence immune maturation and allergy development. We therefore aimed to associate infant and maternal metabolomes to T- and B-cell subpopulations and allergy diagnosis. We performed liquid chromatography-mass spectrometry based untargeted metabolomics on blood plasma from mothers (third trimester, n = 605; delivery, n = 558) and from the umbilical cord (n = 366). The measured metabolomes were associated to T- and B-cell subpopulations up to 4 months after delivery and to doctor´s diagnosed eczema, food allergy and asthma at one year of age using random forest analysis. Maternal and cord plasma at delivery could predict the number of CD24+CD38low memory B-cells (p = 0.033, n = 26 and p = 0.009, n = 22), but future allergy status could not be distinguished from any of the three measured metabolomes. Replication of previous literature findings showed hypoxanthine to be upregulated in the umbilical cord of children with subsequent asthma. This exploratory study suggests foetal immune programming occuring during pregnancy as the metabolomic profiles of mothers and infants at delivery related to infants’ B-cell maturation.
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22. |
- Hartvigsson, Olle, 1991, et al.
(författare)
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Associations of the placental metabolome with immune maturation up to one year of age in the Swedish NICE-cohort
- 2024
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Ingår i: Metabolomics. - : Springer Nature. - 1573-3882 .- 1573-3890. ; 20:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Allergies and other immune-mediated diseases are thought to result from incomplete maturation of the immune system early in life. We previously showed that infants’ metabolites at birth were associated with immune cell subtypes during infancy. The placenta supplies the fetus with nutrients, but may also provide immune maturation signals. Objectives: To examine the relationship between metabolites in placental villous tissue and immune maturation during the first year of life and infant and maternal characteristics (gestational length, birth weight, sex, parity, maternal age, and BMI). Methods: Untargeted metabolomics was measured using Liquid Chromatography-Mass Spectrometry. Subpopulations of T and B cells were measured using flow cytometry at birth, 48 h, one, four, and 12 months. Random forest analysis was used to link the metabolomics data with the T and B cell sub populations as well as infant and maternal characteristics. Results: Modest associations (Q2 = 0.2–0.3) were found between the placental metabolome and kappa-deleting recombination excision circles (KREC) at birth and naïve B cells and memory T cells at 12 months. Weak associations were observed between the placental metabolome and sex and parity. Still, most metabolite features of interest were of low intensity compared to associations previously found in cord blood, suggesting that underlying metabolites were not of placental origin. Conclusion: Our results indicate that metabolomic measurements of the placenta may not effectively recognize metabolites important for immune maturation.
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23. |
- 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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24. |
- Hålldin, Elin, et al.
(författare)
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Factors Explaining Interpersonal Variation in Plasma Enterolactone Concentrations in Humans
- 2019
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Ingår i: Molecular Nutrition and Food Research. - : Wiley. - 1613-4125 .- 1613-4133. ; 63:16
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Forskningsöversikt (refereegranskat)abstract
- Lignans are diphenolic plant compounds with potential health modulating properties that are absorbed to the circulation and metabolized to the enterolignans enterodiol (END) and enterolactone (ENL) by gut microbiota. Epidemiological studies have inconsistently shown that a high lignan intake and circulating ENL are associated with reduced risk of breast-, prostate-, and colorectal cancer as well as cardiovascular disease and total and cause-specific mortality. Inconsistencies can be due to interpersonal variation of ENL formation or responses. The aim of this review is to identify and evaluate the impact of factors influencing variability in plasma concentrations of the main enterolignan, ENL. The main determinants of plasma ENL concentrations are intake of lignan and lignan-rich foods, composition and activity of intestinal microflora, antimicrobial use, nutrient intake, BMI, smoking, sex, and age. Composition and activity of the intestinal microbiota appear to be the most critical factor governing interpersonal variability in plasma ENL concentration followed by the use of antibiotics. Future studies with combined data from gut microbiota and metabolomics with food intake and life style data can be used to estimate the relative contribution of the different factors to ENL concentration in quantitative terms.
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25. |
- Iversen, Kia Noehr, 1987, et al.
(författare)
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Appetite and Subsequent Food Intake Were Unaffected by the Amount of Sourdough and Rye in Soft Bread-A Randomized Cross-Over Breakfast Study
- 2018
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 10:11
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Tidskriftsartikel (refereegranskat)abstract
- Sourdough fermented bread has been suggested to have beneficial health effects, in part mediated by increased satiety in the postprandial phase, but only limited research has been conducted to verify this. The current study aimed to investigate the effect of the amounts of sourdough and rye in soft bread on postprandial appetite. On 6 occasions, 23 healthy volunteers consumed 5 different test breads, with varying amount of rye and sourdough, and a yeast-fermented refined wheat control bread as part of a breakfast meal. The sourdough ranged between 9⁻51% of dough weight and rye content between 35⁻48% of flour weight. Appetite was recorded using visual analogue scales from immediately before breakfast and every 30 min the following 4 h. An ad libitum lunch was served 4 h after the breakfast meal, from which voluntary energy intake was measured. While some of the test breads resulted in lower hunger ratings and increased sense of fullness compared to the refined wheat bread, there were no differences between the test breads. The content of rye in the test breads differed within a narrow range, which might explain the lack of a consistent effect of rye on appetite. Microstructural examination of the test breads showed an increased aggregation of proteins in the breads with high content of sourdough, indicating additional changes to the breads, beyond change in pH, which may counteract the potential effect of decreased pH in the bread on appetite. In conclusion, our study does not support an effect of sourdough on appetite and ad libitum food intake.
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26. |
- Klåvus, Anton, et al.
(författare)
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“Notame”: Workflow for non-targeted LC-MS metabolic profiling
- 2020
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989 .- 2218-1989. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Metabolomics analysis generates vast arrays of data, necessitating comprehensive workflows involving expertise in analytics, biochemistry and bioinformatics in order to provide coherent and high-quality data that enable discovery of robust and biologically significant metabolic findings. In this protocol article, we introduce notame, an analytical workflow for non-targeted metabolic profiling approaches, utilizing liquid chromatography-mass spectrometry analysis. We provide an overview of lab protocols and statistical methods that we commonly practice for the analysis of nutritional metabolomics data. The paper is divided into three main sections: the first and second sections introducing the background and the study designs available for metabolomics research and the third section describing in detail the steps of the main methods and protocols used to produce, preprocess and statistically analyze metabolomics data and, finally, to identify and interpret the compounds that have emerged as interesting.
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27. |
- Kyro, Cecilie, et al.
(författare)
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Alkylresorcinols (biomarkers of whole grain intake), cereal fibre intake and metabolic profile - results from a European study
- 2020
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Ingår i: Proceedings of the Nutrition Society. - : Cambridge University Press. - 0029-6651 .- 1475-2719. ; 79:OCE2, s. E648-E648
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: High intakes of whole-grains and cereal fiber have been consistently associated with lower risk of cardiometabolic diseases in observational studies. Yet, improved understanding about the underlying mechanisms is needed. We hypothesized that cereal fiber and whole-grain are associated with beneficial metabolic marker profiles.Aim: To investigate if cereal fiber intake, estimated by food frequency questionnaires and plasma total alkylresorcinols concentrations as well as the C17:0/C21:0-ratio in plasma as biomarkers of whole-grain wheat and rye intake or the relative whole-grain rye to wheat intake, respectively, were associated with metabolic biomarkers.Design: A cross-sectional study conducted to investigate the associations between alkylresorcinols as biomarker of whole-grain wheat and rye intake, cereal fiber and selected metabolic biomarkers among 954 participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cereal fiber intake was assessed by FFQ and whole grain wheat and rye were reflected by biomarkers analyzed in plasma samples, i.e. total alkylresorcinol (AR). Moreover, the ratio of two of the five measured alkylresorcinols (AR C17:0/C21:0 ratio) was used as an indicator of whole-grain source (wheat or rye). Metabolic biomarkers (HbA1c, C-peptide, IGFBP-1, IGFBP-2, total cholesterol, LDL, HDL, triglycerides, apolipoprotein A-I (apoA), apolipoprotein B (ApoB) and CRP) were measured in blood samples. All biomarkers were already measured for nested case-control studies of colorectal cancer matched based on sex, study center, age at blood collection, date and time of blood collection, fasting status. Women were further matched by menopausal status, phase of menstrual cycle, and use of oral contraceptives or hormone replacement therapy at time of blood collection. Multivariable linear regression analysis was used to investigate the relationship between exposure variables metabolic biomarkers adjusted for case-control status and common confounders.Results: No associations were found between cereal fiber intake and the metabolic markers. However, whole-grain wheat and rye intake, reflected by total AR, was associated with a lower concentration of the inflammation marker CRP. The alkylresorcinol C17:0/C21:0 ratio was not associated with any of the measured metabolic markers in this cohort.Conclusion: Overall, we found no support for an association between cereal fibre intake, whole grain wheat and rye intake reflected by biomarkers and metabolic markers in the present cohort. One exception was the finding of an inverse association between whole grain biomarkers and CRP. Prospective studies or RCTs are warranted to confirm our findings.
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28. |
- Li, Wenyun, et al.
(författare)
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Personalized microbial fingerprint associated with differential glycemic effects of a whole grain rye intervention on Chinese adults
- 2024
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Ingår i: Molecular Nutrition & Food Research. - : John Wiley & Sons. - 1613-4125 .- 1613-4133.
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Tidskriftsartikel (refereegranskat)abstract
- Scope: This study aims to identify the gut enterotypes that explain differential responses to intervention with whole grain rye by proposing an “enterotype - metabolic” model.Methods and results: A 12-week randomized controlled trial is conducted in Chinese adults, with 79 subjects consuming whole grain products with fermented rye bran (FRB) and 77 consuming refined wheat products in this exploratory post-hoc analysis. Responders or non-responders are identified according to whether blood glucose decreased by more than 10% after rye intervention. Compared to non-responders, responders in FRB have higher baseline Bacteroides (p < 0.001), associated with reduced blood glucose (p < 0.001), increased Faecalibacterium (p = 0.020) and Erysipelotrichaceae_UCG.003 (p = 0.022), as well as deceased 7β-hydroxysteroid dehydrogenase (p = 0.033) after intervention. The differentiated gut microbiota and metabolites between responders and non-responders after intervention are enriched in aminoacyl-tRNA biosynthesis.Conclusion: The work confirms the previously suggested importance of microbial enterotypes in differential responses to whole grain interventions and supports taking enterotypes into consideration for improved efficacy of whole grain intervention for preventing type 2 diabetes. Altered short-chain fatty acids and bile acid metabolism might be a potential mediator for the beneficial effects of whole grain rye on glucose metabolism.
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29. |
- Madawala, Samanthi R.P., et al.
(författare)
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Impact of location on composition of selected phytochemicals in wild sea buckthorn (Hippophae rhamnoides)
- 2018
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Ingår i: Journal of Food Composition and Analysis. - : Elsevier BV. - 0889-1575 .- 1096-0481. ; 72, s. 115-121
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Tidskriftsartikel (refereegranskat)abstract
- Sea buckthorn (Hippophae rhamnoides; SB) is rich in many essential nutrients and an ideal crop for the sub-Himalayan region in India, as well as other marginal lands with extreme weather conditions. Naturally growing SB from selected geographical locations in India and Sweden were evaluated for total lipid content, fatty acid composition, carotenoids, tocopherols, sterols and phenolic compounds, as well as for untargeted metabolite profiles. Principal component and partial least squares analyses of targeted data showed similar distinctions between Swedish and Indian locations in the first component, attributed to differences in total lipids, individual fatty acids and phenols. The second component distinguished between Indian locations, predominantly due to differences in fatty acids, sitostanol, lutein and caffeic acid. Untargeted analysis by LC–MS metabolomics analysis confirmed that variability from targeted analysis was representative of overall variability. All analyses of targeted and untargeted data indicated a large systematic variability in phytochemicals in relation to sampling location. The results have implications for optimisation of agronomical factors for differential use of SB as a source for food and nutraceuticals and further downstream for increased profitability for the sub-Himalayan and other regions with suitable growing conditions for sea buckthorn. The results also clearly showed that differences between locations were well captured with a few targeted analyses.
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30. |
- Madrid-Gambin, Francisco, et al.
(författare)
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Untargeted 1H NMR-Based Metabolomics Analysis of Urine and Serum Profiles after Consumption of Lentils, Chickpeas, and Beans: An Extended Meal Study to Discover Dietary Biomarkers of Pulses
- 2018
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Ingår i: Journal of Agricultural and Food Chemistry. - : American Chemical Society (ACS). - 0021-8561 .- 1520-5118. ; 66:27, s. 6997-7005
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Tidskriftsartikel (refereegranskat)abstract
- High legume intake has been shown to have beneficial effects on the health of humans. The use of nutritional biomarkers, as a complement to self-reported questionnaires, could assist in evaluating dietary intake and downstream effects on human health. The aim of this study was to investigate potential biomarkers of the consumption of pulses (i.e., white beans, chickpeas, and lentils) by using untargeted NMR-based metabolomics. Meals rich in pulses were consumed by a total of 11 participants in a randomized crossover study and multilevel partial least-squares regression was employed for paired comparisons. Metabolomics analysis indicated that trigonelline, 3-methylhistidine, dimethylglycine, trimethylamine, and lysine were potential, though not highly specific, biomarkers of pulse intake. Furthermore, monitoring of these metabolites for a period of 48 h after intake revealed a range of different excretion patterns among pulses. Following the consumption of pulses, a metabolomic profiling revealed that the concentration ratios of trigonelline, choline, lysine, and histidine were similar to those found in urine. In conclusion, this study identified potential urinary biomarkers of exposure to dietary pulses and provided valuable information about the time-response effect of these putative biomarkers.
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31. |
- 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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32. |
- Noerman, Stefania, 1987, et al.
(författare)
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Associations of the serum metabolite profile with a healthy Nordic diet and risk of coronary artery disease
- 2021
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 1532-1983 .- 0261-5614. ; 40:5, s. 3250-3262
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Tidskriftsartikel (refereegranskat)abstract
- Background & aim: A healthy Nordic diet (HND) rich in wholegrain cereals, berries, vegetables, and fish, has been associated with a lower risk of cardiovascular disease, but the molecular links remain unclear. Here, we present the application of nontargeted metabolic profiling based on liquid chromatography with tandem mass spectrometry (LC-MS/MS) to identify metabolites that would potentially reflect the adherence to HND and their relationship with the risk of coronary artery disease (CAD). Methods: From a Finnish population-based prospective cohort (Kuopio Ischaemic Heart Disease Risk Factor Study; KIHD), we collected 364 baseline serum samples in 4 groups: 1) 94 participants with high adherence to HND who developed CAD during the follow-up of 20.4 ± 7.6 years (cases), 2) 88 participants with high adherence who did not develop CAD during follow-up (controls), 3) 93 CAD cases with low adherence, and 4) 89 controls with low adherence. Results: Indolepropionic acid, proline betaine, vitamin E derivatives, and medium-chain acylcarnitines were associated with adherence to HND after adjustments for age, waist-to-hip ratio (WHR), physical activity, and total cholesterol. These metabolites also correlated negatively with blood lipid profiles, BMI, insulin, inflammation marker high-sensitivity C reactive protein (hsCRP), smoking, and alcohol consumption, as well as positively with physical activity. Predictors of CAD risk included several lipid molecules, which also indicated lower adherence to HND. But, only the associations with the plasmalogens PC(O-16:0/18:2) and PC(O-16:1/18:2) remained significant after adjusting for age, smoking, systolic blood pressure, LDL cholesterol, and WHR. These plasmalogens did not correlate with any investigated risk factors of CAD at baseline, which may highlight their potential as novel predictors of CAD risk. Interestingly, the metabolic profile predicting CAD risk differed based on the adherence to HND. Also, HND adherence was more distinct within CAD cases than controls, which may emphasize the interaction between HND adherence and CAD risk. Conclusions: The association between higher adherence to HND and a lower risk of CAD likely involves a complex interaction of various endogenous, plant-, and microbial-derived metabolites.
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33. |
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34. |
- Noerman, Stefania, 1987, et al.
(författare)
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Fasting plasma metabolites reflecting meat consumption and their associations with incident type 2 diabetes in two Swedish cohorts
- 2024
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Ingår i: The American journal of clinical nutrition. - : Elsevier. - 0002-9165 .- 1938-3207. ; 119:5, s. 1280-1292
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Tidskriftsartikel (refereegranskat)abstract
- Background: Consumption of processed red meat has been associated with increased risk of developing type 2 diabetes (T2D), but challenges in dietary assessment call for objective intake biomarkers. Objectives: This study aimed to investigate metabolite biomarkers of meat intake and their associations with T2D risk. Methods: Fasting plasma samples were collected from a case–control study nested within Västerbotten Intervention Program (VIP) (214 females and 189 males) who developed T2D after a median follow-up of 7 years. Panels of biomarker candidates reflecting the consumption of total, processed, and unprocessed red meat and poultry were selected from the untargeted metabolomics data collected on the controls. Observed associations were then replicated in Swedish Mammography clinical subcohort in Uppsala (SMCC) (n = 4457 females). Replicated metabolites were assessed for potential association with T2D risk using multivariable conditional logistic regression in the discovery and Cox regression in the replication cohorts. Results: In total, 15 metabolites were associated with ≥1 meat group in both cohorts. Acylcarnitines 8:1, 8:2, 10:3, reflecting higher processed meat intake [r > 0.22, false discovery rate (FDR) < 0.001 for VIP and r > 0.05; FDR < 0.001 for SMCC) were consistently associated with higher T2D risk in both data sets. Conversely, lysophosphatidylcholine 17:1 and phosphatidylcholine (PC) 15:0/18:2 were associated with lower processed meat intake (r < −0.12; FDR < 0.023, for VIP and r < −0.05; FDR < 0.001, for SMCC) and with lower T2D risk in both data sets, except for PC 15:0/18:2, which was significant only in the VIP cohort. All associations were attenuated after adjustment for BMI (kg/m2). Conclusions: Consistent associations of biomarker candidates involved in lipid metabolism between higher processed red meat intake with higher T2D risk and between those reflecting lower intake with the lower risk may suggest a relationship between processed meat intake and higher T2D risk. However, attenuated associations after adjusting for BMI indicates that such a relationship may at least partly be mediated or confounded by BMI.
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35. |
- Noerman, Stefania, 1987, et al.
(författare)
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Serum metabolites associated with wholegrain consumption using nontargeted metabolic profiling: a discovery and reproducibility study
- 2023
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 62:2, s. 713-726
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To identify fasting serum metabolites associated with WG intake in a free-living population adjusted for potential confounders. Methods: We selected fasting serum samples at baseline from a subset (n = 364) of the prospective population-based Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) cohort. The samples were analyzed using nontargeted metabolomics with liquid chromatography coupled with mass spectrometry (LC–MS). Association with WG intake was investigated using both random forest followed by linear regression adjusted for age, BMI, smoking, physical activity, energy and alcohol consumption, and partial Spearman correlation adjusted for the same covariates. Features selected by any of these models were shortlisted for annotation. We then checked if we could replicate the findings in an independent subset from the same cohort (n = 200). Results: Direct associations were observed between WG intake and pipecolic acid betaine, tetradecanedioic acid, four glucuronidated alkylresorcinols (ARs), and an unknown metabolite both in discovery and replication cohorts. The associations remained significant (FDR<0.05) even after adjustment for the confounders in both cohorts. Sinapyl alcohol was positively correlated with WG intake in both cohorts after adjustment for the confounders but not in linear models in the replication cohort. Some microbial metabolites, such as indolepropionic acid, were positively correlated with WG intake in the discovery cohort, but the correlations were not replicated in the replication cohort. Conclusions: The identified associations between WG intake and the seven metabolites after adjusting for confounders in both discovery and replication cohorts suggest the potential of these metabolites as robust biomarkers of WG consumption.
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36. |
- Nordin, Elise, 1985, et al.
(författare)
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Effects of FODMAPs and Gluten on Gut Microbiota and Their Association with the Metabolome in Irritable Bowel Syndrome: A Double-Blind, Randomized, Cross-Over Intervention Study
- 2023
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643 .- 2072-6643. ; 15:13
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Tidskriftsartikel (refereegranskat)abstract
- Background: A mechanistic understanding of the effects of dietary treatment in irritable bowel syndrome (IBS) is lacking. Our aim was therefore to investigate how fermentable oligo- di-, monosaccharides, and polyols (FODMAPs) and gluten affected gut microbiota and circulating metabolite profiles, as well as to investigate potential links between gut microbiota, metabolites, and IBS symptoms. Methods: We used data from a double-blind, randomized, crossover study with week-long provocations of FODMAPs, gluten, and placebo in participants with IBS. To study the effects of the provocations on fecal microbiota, fecal and plasma short-chain fatty acids, the untargeted plasma metabolome, and IBS symptoms, we used Random Forest, linear mixed model and Spearman correlation analysis. Results: FODMAPs increased fecal saccharolytic bacteria, plasma phenolic-derived metabolites, 3-indolepropionate, and decreased isobutyrate and bile acids. Gluten decreased fecal isovalerate and altered carnitine derivatives, CoA, and fatty acids in plasma. For FODMAPs, modest correlations were observed between microbiota and phenolic-derived metabolites and 3-indolepropionate, previously associated with improved metabolic health, and reduced inflammation. Correlations between molecular data and IBS symptoms were weak. Conclusions: FODMAPs, but not gluten, altered microbiota composition and correlated with phenolic-derived metabolites and 3-indolepropionate, with only weak associations with IBS symptoms. Thus, the minor effect of FODMAPs on IBS symptoms must be weighed against the effect on microbiota and metabolites related to positive health factors.
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37. |
- Nordin, Elise, 1985, et al.
(författare)
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Exploration of differential responses to FODMAPs and gluten in people with irritable bowel syndrome- a double-blind randomized cross-over challenge study
- 2024
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Ingår i: Metabolomics. - : Springer. - 1573-3882 .- 1573-3890. ; 20:2
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Tidskriftsartikel (refereegranskat)abstract
- There is large variation in response to diet in irritable bowel syndrome (IBS) and determinants for differential response are poorly understood. Objectives Our aim was to investigate differential clinical and molecular responses to provocation with fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) and gluten in individuals with IBS. Methods Data were used from a crossover study with week-long interventions with either FODMAPs, gluten or placebo. The study also included a rapid provocation test. Molecular data consisted of fecal microbiota, short chain fatty acids, and untargeted plasma metabolomics. IBS symptoms were evaluated with the IBS severity scoring system. IBS symptoms were modelled against molecular and baseline questionnaire data, using Random Forest (RF; regression and clustering), Parallel Factor Analysis (PARAFAC), and univariate methods. Results Regression and classification RF models were in general of low predictive power (Q2 <= 0.22, classification rate < 0.73). Out of 864 clustering models, only 2 had significant associations to clusters (0.69 < CR < 0.73, p < 0.05), but with no associations to baseline clinical measures. Similarly, PARAFAC revealed no clear association between metabolome data and IBS symptoms. Conclusion Differential IBS responses to FODMAPs or gluten exposures could not be explained from clinical and molecular data despite extensive exploration with different data analytical approaches. The trial is registered at www.clinicaltrials.gov as NCT03653689 31/08/2018.
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38. |
- 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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39. |
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40. |
- Nordin, Elise, 1985, et al.
(författare)
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IBS randomized study : FODMAPs alter bile acids, phenolic- and tryptophan metabolites, while gluten modifies lipids
- 2023
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - : American Physiological Society. - 0363-6119 .- 1522-1490. ; 325:3, s. R248-R259
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Tidskriftsartikel (refereegranskat)abstract
- Diet is considered a culprit for symptoms in irritable bowel syndrome (IBS), although the mechanistic understanding of underlying causes is lacking. Metabolomics, i.e., the analysis of metabolites in biological samples may offer a diet-responsive fingerprint for IBS. Our aim was to explore alterations in the plasma metabolome after interventions with fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) or gluten versus control in IBS, and to relate such alterations to symptoms. People with IBS (n = 110) were included in a double-blind, randomized, crossover study with 1-wk provocations of FODMAPs, gluten, or placebo. Symptoms were evaluated with the IBS severity scoring system (IBS-SSS). Untargeted metabolomics was performed on plasma samples using LC-qTOF-MS. Discovery of metabolite alterations by treatment was performed using random forest followed by linear mixed modeling. Associations were studied using Spearman correlation. The metabolome was affected by FODMAP [classification rate (CR) 0.88, P < 0.0001], but less by gluten intake CR 0.72, P = 0.01). FODMAP lowered bile acids, whereas phenolic-derived metabolites and 3-indolepropionic acid (IPA) were higher compared with placebo. IPA and some unidentified metabolites correlated weakly to abdominal pain and quality of life. Gluten affected lipid metabolism weakly, but with no interpretable relationship to IBS. FODMAP affected gut microbial-derived metabolites relating to positive health outcomes. IPA and unknown metabolites correlated weakly to IBS severity. Minor symptom worsening by FODMAP intake must be weighed against general positive health aspects of FODMAP. The gluten intervention affected lipid metabolism weakly with no interpretable association to IBS severity. Registration: www.clinicaltrials.gov as NCT03653689. NEW & NOTEWORTHY In irritable bowel syndrome (IBS), fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) affected microbial-derived metabolites relating to positive health outcomes such as reduced risk of colon cancer, inflammation, and type 2 diabetes, as shown in previous studies. The minor IBS symptom induction by FODMAP intake must be weighed against the positive health aspects of FODMAP consumption. Gluten affected lipids weakly with no association to IBS severity.
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41. |
- 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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42. |
- Palau-Rodriguez, Magali, et al.
(författare)
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Effects of a long-term lifestyle intervention on metabolically healthy women with obesity: Metabolite profiles according to weight loss response
- 2020
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Ingår i: Clinical Nutrition. - : Elsevier BV. - 1532-1983 .- 0261-5614. ; 39:1, s. 215-224
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: The benefits of weight loss in subjects with metabolically healthy obesity (MHO) are still a matter of controversy. We aimed to identify metabolic fingerprints and their associated pathways that discriminate women with MHO with high or low weight loss response after a lifestyle intervention, based on a hypocaloric Mediterranean diet (MedDiet) and physical activity. Methods: A UPLC-Q-Exactive-MS/MS metabolomics workflow was applied to plasma samples from 27 women with MHO before and after 12 months of a hypocaloric weight loss intervention with a MedDiet and increased physical activity. The subjects were stratified into two age-matched groups according to weight loss: <10% (low weight loss group, LWL) and >10% (high weight loss group, HWL). Random forest analysis was performed to identify metabolites discriminating between the LWL and the HWL as well as within-status effects. Modulated pathways and associations between metabolites and anthropometric and biochemical variables were also investigated. Results: Thirteen metabolites discriminated between the LWL and the HWL, including 1,5-anhydroglucitol, carotenediol, 3-(4-hydroxyphenyl)lactic acid, N-acetylaspartate and several lipid species (steroids, a plasmalogen, sphingomyelins, a bile acid and long-chain acylcarnitines). 1,5-anhydroglucitol, 3-(4-hydroxyphenyl)lactic acid and sphingomyelins were positively associated with weight variables whereas N-acetylaspartate and the plasmalogen correlated negatively with them. Changes in very long-chain acylcarnitines and hydroxyphenyllactic levels were observed in the HWL and positively correlated with fasting glucose, and changes in levels of the plasmalogen negatively correlated with insulin resistance. Additionally, the cholesterol profile was positively associated with changes in acid hydroxyphenyllactic, sphingolipids and 1,5-AG. Conclusions: Higher weight loss after a hypocaloric MedDiet and increased physical activity for 12 months is associated with changes in the plasma metabolome in women with MHO. These findings are associated with changes in biochemical variables and may suggest an improvement of the cardiometabolic risk profile in those patients that lose greater weight. Further studies are needed to investigate whether the response of those subjects with MHO to this intervention differs from those with unhealthy obesity.
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43. |
- Palmnäs, Marie, 1988, et al.
(författare)
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Perspective: Metabotyping—A Potential Personalized Nutrition Strategy for Precision Prevention of Cardiometabolic Disease
- 2020
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Ingår i: Advances in nutrition (Bethesda, Md.). - : Elsevier BV. - 2161-8313 .- 2156-5376. ; 11:3, s. 524-532
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Forskningsöversikt (refereegranskat)abstract
- Diet is an important, modifiable lifestyle factor of cardiometabolic disease risk, and an improved diet can delay or even prevent the onset of disease. Recent evidence suggests that individuals could benefit from diets adapted to their genotype and phenotype: that is, personalized nutrition. A novel strategy is to tailor diets for groups of individuals according to their metabolic phenotypes (metabotypes). Randomized controlled trials evaluating metabotype-specific responses and nonresponses are urgently needed to bridge the current gap of knowledge with regard to the efficacy of personalized strategies in nutrition. In this Perspective, we discuss the concept of metabotyping, review the current literature on metabotyping in the context of cardiometabolic disease prevention, and suggest potential strategies for metabotype-based nutritional advice for future work. We also discuss potential determinants of metabotypes, including gut microbiota, and highlight the use of metabolomics to define effective markers for cardiometabolic disease-related metabotypes. Moreover, we hypothesize that people at high risk for cardiometabolic diseases have distinct metabotypes and that individuals grouped into specific metabotypes may respond differently to the same diet, which is being tested in a project of the Joint Programming Initiative: A Healthy Diet for a Healthy Life.
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44. |
- 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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45. |
- Ribbenstedt, Anton, et al.
(författare)
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In-plate toxicometabolomics of single zebrafish embryos
- 2020
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Ingår i: Molecular Omics. - : Royal Society of Chemistry (RSC). - 2515-4184. ; 16:3, s. 185-194
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Tidskriftsartikel (refereegranskat)abstract
- Toxicometabolomic studies involving zebrafish embryos have become increasingly popular for linking apical endpoints to biochemical perturbations as part of adverse outcome pathway determination. These experiments involve pooling embryos to generate sufficient biomass for metabolomic measurement, which adds both time and cost. To address this limitation, we developed a high-throughput toxicometabolomic assay involving single zebrafish embryos. Incubation, microscopy, embryo extraction, and instrumental metabolomic analysis were all performed in the same 96-well plate, following acquisition of conventional toxicological endpoints. The total time for the assay (including testing of 6 doses/n= 12 embryos per dose plus positive and negative controls, assessing conventional endpoints, instrumental analysis, data processing and multivariate statistics) is <14 days. Metabolomic perturbations at low dose were linked statistically to those observed at high dose and in the presence of an adverse effect, thereby contextualizing omic data amongst apical endpoints. Overall, this assay enables collection of high resolution metabolomic data in a high throughput manner, suitable for mode of action hypothesis generation in the context of pharmaceutical or toxicological screening.
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46. |
- 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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47. |
- 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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48. |
- Rostgaard-Hansen, Agnetha, 1986, et al.
(författare)
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Relative Validity and Reproducibility of a Web-Based Semi-Quantitative Food Frequency Questionnaire in the Danish Diet, Cancer, and Health—Next Generations MAX Study
- 2023
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Ingår i: Nutrients. - 2072-6643 .- 2072-6643. ; 15:10
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Tidskriftsartikel (refereegranskat)abstract
- The food frequency questionnaire (FFQ) is designed to capture an individual’s habitual dietary intake and is the most applied method in nutritional epidemiology. Our aim was to assess the relative validity and reproducibility of the FFQ used in the Diet, Cancer, and Health—Next Generations cohort (DCH-NG). We included 415 Danish women and men aged 18–67 years. Spearman’s correlations coefficients, Bland–Altman limits of agreement and cross-classification between dietary intakes estimated from the FFQ administered at baseline (FFQbaseline), and the mean of three 24-h dietary recalls (24-HDRs) and the FFQ administered after 12 months (FFQ12 months) were determined. Nutrient intakes were energy-adjusted by Nutrient Density and Residual methods. Correlation coefficients ranged from 0.18–0.58 for energy and energy-adjusted nutrient intakes, and the percentage of participants classified into the same quartile ranged from 28–47% between the FFQbaseline and the 24-HDRs. For the FFQ12 months compared with FFQbaseline, correlation coefficients ranged from 0.52–0.88 for intakes of energy, energy-adjusted nutrients, and food groups, and the proportion of participants classified into the same quartiles ranged from 43–69%. Overall, the FFQ provided a satisfactory ranking of individuals according to energy, nutrient, and food group intakes, making the FFQ suitable for use in epidemiological studies investigating diet in relation to disease outcomes.
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49. |
- Rostgaard-Hansen, Agnetha, 1986, et al.
(författare)
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Temporal gut microbiota variability and association with dietary patterns : from the one-year observational Diet, cancer, and health - Next generations MAX study
- 2024
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Ingår i: American Journal of Clinical Nutrition. - : Elsevier. - 0002-9165 .- 1938-3207. ; 119:4, s. 1015-1026
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Tidskriftsartikel (refereegranskat)abstract
- Background: Knowledge about the variability of gut microbiota within an individual over time is important to allow meaningful investigations of the gut microbiota in relation to diet and health outcomes in observational studies. Plant-based dietary patterns have been associated with a lower risk of morbidity and mortality and may alter gut microbiota in a favorable direction.Objectives: To assess the gut microbiota variability during one year and investigate the association between adherence to diet indexes and the gut microbiota in a Danish population.Methods: Four hundred forty-four participants were included in the Diet, Cancer, and Health - Next Generations MAX study (DCH-NG MAX). Stool samples collected up to three times during a year were analyzed by 16S ribosomal ribonucleic acid gene sequencing. Diet was obtained by 24-hour dietary recalls. Intraclass correlation coefficient (ICC) was calculated to assess temporal microbial variability based on 214 individuals. Diet indexes (Nordic, Mediterranean, and plant-based diets) and food groups thereof were associated with gut microbiota using linear regression analyses.Results: We found that 91 out of 234 genera had an ICC >0.5. We identified three subgroups dominated by Bacteroides, Prevotella 9, and Ruminococcaceae and adherence to diet indexes differed between subgroups. Higher adherence to diet indexes was associated with the relative abundance of 22 genera. Across diet indexes, higher intakes of fruit, vegetables, whole grains/cereals, and nuts were most frequently associated with these genera.Conclusions: In the DCH-NG MAX study, 39% of the genera had an ICC >0.5 over one year, suggesting that these genera could be studied with health outcomes in prospective analyses with acceptable precision. Adherence to the Nordic, Mediterranean, and plant-based diets differed between bacterial subgroups and was associated with a higher abundance of genera with fiber-degrading properties. Fruits, vegetables, whole grains/cereals, and nuts were frequently associated with these genera.
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50. |
- Schillemans, Tessa, et al.
(författare)
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Associations of PFAS-related plasma metabolites with cholesterol and triglyceride concentrations
- 2023
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 216
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Tidskriftsartikel (refereegranskat)abstract
- The wide-spread environmental pollutants per- and polyfluoroalkyl substances (PFAS) have repeatedly been associated with elevated serum cholesterol in humans. However, underlying mechanisms are still unclear. Furthermore, we have previously observed inverse associations with plasma triglycerides. To better understand PFAS-induced effects on lipid pathways we investigated associations of PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations. We used 290 PFAS-related metabolite features that we previously discovered from untargeted liquid chromatography-mass spectometry metabolomics in a case-control study within the Swedish Västerbotten Intervention Programme cohort. Herein, we studied associations of these PFAS-related metabolite features with plasma cholesterol and triglyceride concentrations in plasma samples from 187 healthy control subjects collected on two occasions between 1991 and 2013. The PFAS-related features did not associate with cholesterol, but 50 features were associated with triglycerides. Principal component analysis on these features indicated that one metabolite pattern, dominated by glycerophospholipids, correlated with longer chain PFAS and associated inversely with triglycerides (both cross-sectionally and prospectively), after adjustment for confounders. The observed time-trend of the metabolite pattern resembled that of the longer chain PFAS, with higher levels during the years 2004–2010. Mechanisms linking PFAS exposures to triglycerides may thus occur via longer chain PFAS affecting glycerophospholipid metabolism. If the results reflect a cause-effect association, as implied by the time-trend and prospective analyses, this may affect the general adult population.
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