| 1. |
- Forslund, Sofia K., et al.
(författare)
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Combinatorial, additive and dose-dependent drug–microbiome associations
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505
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Tidskriftsartikel (refereegranskat)abstract
- During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease.
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| 2. |
- Molinaro, Antonio, et al.
(författare)
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Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism. Here, we show that subjects with prediabetes and diabetes in the MetaCardis cohort from three European countries have elevated serum imidazole propionate levels. Furthermore, imidazole propionate levels were increased in subjects with low bacterial gene richness and Bacteroides 2 enterotype, which have previously been associated with obesity. The Bacteroides 2 enterotype was also associated with increased abundance of the genes involved in imidazole propionate biosynthesis from dietary histidine. Since patients and controls did not differ in their histidine dietary intake, the elevated levels of imidazole propionate in type 2 diabetes likely reflects altered microbial metabolism of histidine, rather than histidine intake per se. Thus the microbiota may contribute to type 2 diabetes by generating imidazole propionate that can modulate host inflammation and metabolism.
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| 3. |
- Andrikopoulos, Petros, et al.
(författare)
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Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
- 2023
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Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.
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| 4. |
- Blundell, John E, et al.
(författare)
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Variations in the Prevalence of Obesity Among European Countries, and a Consideration of Possible Causes.
- 2017
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Ingår i: Obesity facts. - : S. Karger AG. - 1662-4033 .- 1662-4025. ; 10:1, s. 25-37
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Tidskriftsartikel (refereegranskat)abstract
- Over the last 10 years the prevalence of obesity across the European continent has in general been rising. With the exception of a few countries where a levelling-off can be perceived, albeit at a high level, this upward trend seems likely to continue. However, considerable country to country variation is noticeable, with the proportion of people with obesity varying by 10% or more. This variation is intriguing and suggests the existence of different profiles of risk or protection factors operating in different countries. The identification of such protection factors could indicate suitable targets for interventions to help manage the obesity epidemic in Europe. This report is the output of a 2-day workshop on the 'Diversity of Obesity in Europe'. The workshop included 14 delegates from 12 different European countries. This report contains the contributions and discussions of the materials and viewpoints provided by these 14 experts; it is not the output of a single mind. However, such is the nature of scientific analysis regarding obesity that it is possible that a different set of 14 experts may have come to a different set of conclusions. Therefore the report should not be seen as a definitive statement of a stable situation. Rather it is a focus for discussion and comment, and a vehicle to drive forward further understanding and management of obesity in Europe.
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| 5. |
- Chaix, Basile, et al.
(författare)
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Associations of Supermarket Characteristics with Weight Status and Body Fat: A Multilevel Analysis of Individuals within Supermarkets (RECORD Study)
- 2012
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Previous research on the influence of the food environment on weight status has often used impersonal measures food environment defined for residential neighborhoods, which ignore whether people actually use the food outlets near their residence. To assess whether supermarkets are relevant contexts for interventions, the present study explored between-residential neighborhood and between-supermarket variations in body mass index (BMI) and waist circumference (WC), and investigated associations between brands and characteristics of supermarkets and BMI or WC, after adjustment for individual and residential neighborhood characteristics. Methods: Participants in the RECORD Cohort Study (Paris Region, France, 2007-2008) were surveyed on the supermarket (brand and exact location) where they conducted their food shopping. Overall, 7 131 participants shopped in 1 097 different supermarkets. Cross-classified multilevel linear models were estimated for BMI and WC. Results: Just 11.4% of participants shopped for food primarily within their residential neighborhood. After accounting for participants' residential neighborhood, people shopping in the same supermarket had a more comparable BMI and WC than participants shopping in different supermarkets. After adjustment for individual and residential neighborhood characteristics, participants shopping in specific supermarket brands, in hard discount supermarkets (especially if they had a low education), and in supermarkets whose catchment area comprised low educated residents had a higher BMI/WC. Conclusion: A public health strategy to reduce excess weight may be to intervene on specific supermarkets to change food purchasing behavior, as supermarkets are where dietary preferences are materialized into definite purchased foods.
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| 6. |
- Stocks, Tanja, et al.
(författare)
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Change in Proportional Protein Intake in a 10-Week Energy-Restricted Low- or High-Fat Diet, in Relation to Changes in Body Size and Metabolic Factors
- 2013
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Ingår i: Obesity Facts. - : S. Karger AG. - 1662-4025 .- 1662-4033. ; 6:3, s. 217-227
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Forskningsöversikt (refereegranskat)abstract
- Objective: To investigate in a secondary analysis of a randomised trial the effects of a low-/high-fat diet and reported change from baseline in energy% from protein (prot%), in relation to changes in body size and metabolic factors. Methods: Obese adults (n = 771) were randomised to a 600 kcal energy-deficient low-fat (20-25 fat%) or high-fat (40-45 fat%) diet over 10 weeks. Dietary intake data at baseline and during the intervention were available in 585 completers. We used linear regression to calculate the combined effects of randomised group and groups of prot% change (<-2 /-2 to 2/>2) on outcomes. Results: The low-fat group with >2 prot% increase lost 1.1 kg more weight (p = 0.03) and reduced cholesterol by 0.25 mmol/l more (p = 0.003) than the high-fat group with >2 prot% decrease. These differences were 2.5-fold and 1.8-fold greater than the differences between the low-fat and high-fat groups while not considering prot% change. The high-fat group reduced plasma triglycerides more than the low-fat group, but not compared to those in the low-fat group with >2 units prot% increase (p fat-protein interaction = 0.01). Conclusions: Under energy restriction, participants on a low-fat diet who had increased the percentage energy intake from protein showed the greatest reduction in weight and cholesterol, and a triglyceride reduction equally large to that of participants on a high-fat diet.
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| 7. |
- Stocks, Tanja, et al.
(författare)
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TFAP2B influences the effect of dietary fat on weight loss under energy restriction
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:8, s. e43212-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Numerous gene loci are related to single measures of body weight and shape. We investigated if 55 SNPs previously associated with BMI or waist measures, modify the effects of fat intake on weight loss and waist reduction under energy restriction.Methods and Findings: Randomized controlled trial of 771 obese adults. (Registration: ISRCTN25867281.) One SNP was selected for replication in another weight loss intervention study of 934 obese adults. The original trial was a 10-week 600 kcal/d energy-deficient diet with energy percentage from fat (fat%) in range of 20-25 or 40-45. The replication study used an 8-weeks diet of 880 kcal/d and 20 fat%; change in fat% intake was used for estimation of interaction effects. The main outcomes were intervention weight loss and waist reduction. In the trial, mean change in fat% intake was -12/+4 in the low/high-fat groups. In the replication study, it was -23/-12 among those reducing fat% more/less than the median. TFAP2B-rs987237 genotype AA was associated with 1.0 kg (95% CI, 0.4; 1.6) greater weight loss on the low-fat, and GG genotype with 2.6 kg (1.1; 4.1) greater weight loss on the high-fat (interaction p-value; p=0.00007). The replication study showed a similar (non-significant) interaction pattern. Waist reduction results generally were similar. Study-strengths include (i) the discovery study randomised trial design combined with the replication opportunity (ii) the strict dietary intake control in both studies (iii) the large sample sizes of both studies. Limitations are (i) the low minor allele frequency of the TFAP2B polymorphism, making it hard to investigate non-additive genetic effects (ii) the different interventions preventing identical replication-discovery study designs (iii) some missing data for non-completers and dietary intake. No adverse effects/outcomes or side-effects were observed.Conclusions: Under energy restriction, TFAP2B may modify the effect of dietary fat intake on weight loss and waist reduction.
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