1. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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2. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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3. |
- Vieira-Silva, S., et al.
(author)
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Statin therapy is associated with lower prevalence of gut microbiota dysbiosis
- 2020
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 581:7808, s. 310-315
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Journal article (peer-reviewed)abstract
- Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n=888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n=2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
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4. |
- Fromentin, S., et al.
(author)
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Microbiome and metabolome features of the cardiometabolic disease spectrum
- 2022
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In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 28:2, s. 303-314
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Journal article (peer-reviewed)abstract
- By studying individuals along a spectrum of cardiometabolic disease and adjusting for effects of lifestyle and medication, this investigation identifies alterations of the metabolome and microbiome from dysmetabolic conditions, such as obesity and type 2 diabetes, to ischemic heart disease. Previous microbiome and metabolome analyses exploring non-communicable diseases have paid scant attention to major confounders of study outcomes, such as common, pre-morbid and co-morbid conditions, or polypharmacy. Here, in the context of ischemic heart disease (IHD), we used a study design that recapitulates disease initiation, escalation and response to treatment over time, mirroring a longitudinal study that would otherwise be difficult to perform given the protracted nature of IHD pathogenesis. We recruited 1,241 middle-aged Europeans, including healthy individuals, individuals with dysmetabolic morbidities (obesity and type 2 diabetes) but lacking overt IHD diagnosis and individuals with IHD at three distinct clinical stages-acute coronary syndrome, chronic IHD and IHD with heart failure-and characterized their phenome, gut metagenome and serum and urine metabolome. We found that about 75% of microbiome and metabolome features that distinguish individuals with IHD from healthy individuals after adjustment for effects of medication and lifestyle are present in individuals exhibiting dysmetabolism, suggesting that major alterations of the gut microbiome and metabolome might begin long before clinical onset of IHD. We further categorized microbiome and metabolome signatures related to prodromal dysmetabolism, specific to IHD in general or to each of its three subtypes or related to escalation or de-escalation of IHD. Discriminant analysis based on specific IHD microbiome and metabolome features could better differentiate individuals with IHD from healthy individuals or metabolically matched individuals as compared to the conventional risk markers, pointing to a pathophysiological relevance of these features.
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5. |
- Forslund, Sofia K., et al.
(author)
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Combinatorial, additive and dose-dependent drug–microbiome associations
- 2021
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505
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Journal article (peer-reviewed)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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6. |
- Kageyama, Masa, et al.
(author)
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A multi-model CMIP6-PMIP4 study of Arctic sea ice at 127 ka : sea ice data compilation and model differences
- 2021
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In: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 17:1, s. 37-62
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Journal article (peer-reviewed)abstract
- The Last Interglacial period (LIG) is a period with increased summer insolation at high northern latitudes, which results in strong changes in the terrestrial and marine cryosphere. Understanding the mechanisms for this response via climate modelling and comparing the models' representation of climate reconstructions is one of the objectives set up by the Paleoclimate Modelling Intercomparison Project for its contribution to the sixth phase of the Coupled Model Intercomparison Project. Here we analyse the results from 16 climate models in terms of Arctic sea ice. The multi-model mean reduction in minimum sea ice area from the pre industrial period (PI) to the LIG reaches 50 % (multi-model mean LIG area is 3.20×106 km2, compared to 6.46×106 km2 for the PI). On the other hand, there is little change for the maximum sea ice area (which is 15–16×106 km2 for both the PI and the LIG. To evaluate the model results we synthesise LIG sea ice data from marine cores collected in the Arctic Ocean, Nordic Seas and northern North Atlantic. The reconstructions for the northern North Atlantic show year-round ice-free conditions, and most models yield results in agreement with these reconstructions. Model–data disagreement appear for the sites in the Nordic Seas close to Greenland and at the edge of the Arctic Ocean. The northernmost site with good chronology, for which a sea ice concentration larger than 75 % is reconstructed even in summer, discriminates those models which simulate too little sea ice. However, the remaining models appear to simulate too much sea ice over the two sites south of the northernmost one, for which the reconstructed sea ice cover is seasonal. Hence models either underestimate or overestimate sea ice cover for the LIG, and their bias does not appear to be related to their bias for the pre-industrial period. Drivers for the inter-model differences are different phasing of the up and down short-wave anomalies over the Arctic Ocean, which are associated with differences in model albedo; possible cloud property differences, in terms of optical depth; and LIG ocean circulation changes which occur for some, but not all, LIG simulations. Finally, we note that inter-comparisons between the LIG simulations and simulations for future climate with moderate (1 % yr−1) CO2 increase show a relationship between LIG sea ice and sea ice simulated under CO2 increase around the years of doubling CO2. The LIG may therefore yield insight into likely 21st century Arctic sea ice changes using these LIG simulations.
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7. |
- Molinaro, Antonio, et al.
(author)
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Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Journal article (peer-reviewed)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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8. |
- Petersen, Anders Ø., et al.
(author)
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Conjugated C-6 hydroxylated bile acids in serum relate to human metabolic health and gut Clostridia species
- 2021
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 11:1
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Journal article (peer-reviewed)abstract
- Knowledge about in vivo effects of human circulating C-6 hydroxylated bile acids (BAs), also called muricholic acids, is sparse. It is unsettled if the gut microbiome might contribute to their biosynthesis. Here, we measured a range of serum BAs and related them to markers of human metabolic health and the gut microbiome. We examined 283 non-obese and obese Danish adults from the MetaHit study. Fasting concentrations of serum BAs were quantified using ultra-performance liquid chromatography-tandem mass-spectrometry. The gut microbiome was characterized with shotgun metagenomic sequencing and genome-scale metabolic modeling. We find that tauro- and glycohyocholic acid correlated inversely with body mass index (P = 4.1e-03, P = 1.9e-05, respectively), waist circumference (P = 0.017, P = 1.1e-04, respectively), body fat percentage (P = 2.5e-03, P = 2.3e-06, respectively), insulin resistance (P = 0.051, P = 4.6e-4, respectively), fasting concentrations of triglycerides (P = 0.06, P = 9.2e-4, respectively) and leptin (P = 0.067, P = 9.2e-4). Tauro- and glycohyocholic acids, and tauro-a-muricholic acid were directly linked with a distinct gut microbial community primarily composed of Clostridia species (P = 0.037, P = 0.013, P = 0.027, respectively). We conclude that serum conjugated C-6-hydroxylated BAs associate with measures of human metabolic health and gut communities of Clostridia species. The findings merit preclinical interventions and human feasibility studies to explore the therapeutic potential of these BAs in obesity and type 2 diabetes.
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9. |
- Andrikopoulos, Petros, et al.
(author)
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Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide
- 2023
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In: Nature Communications. - 2041-1723 .- 2041-1723. ; 14:1
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Journal article (peer-reviewed)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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10. |
- Corazzini, Kirsten N., et al.
(author)
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Toward Common Data Elements for International Research in Long-term Care Homes : Advancing Person-Centered Care
- 2019
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In: Journal of the American Medical Directors Association. - : Elsevier. - 1525-8610 .- 1538-9375. ; 20:5, s. 598-603
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Journal article (peer-reviewed)abstract
- To support person-centered, residential long-term care internationally, a consortium of researchers in medicine, nursing, behavioral, and social sciences from 21 geographically and economically diverse countries have launched the WE-THRIVE consortium to develop a common data infrastructure. WE-THRIVE aims to identify measurement domains that are internationally relevant, including in low-, middle-, and high-income countries, prioritize concepts to operationalize domains, and specify a set of data elements to measure concepts that can be used across studies for data sharing and comparisons. This article reports findings from consortium meetings at the 2016 meeting of the Gerontological Society of America and the 2017 meeting of the International Association of Gerontology and Geriatrics, to identify domains and prioritize concepts, following best practices to identify common data elements (CDEs) that were developed through the US National Institutes of Health/National Institute of Nursing Research's CDEs initiative. Four domains were identified, including organizational context, workforce and staffing, person-centered care, and care outcomes. Using a nominal group process, WE-THRIVE prioritized 21 concepts across the 4 domains. Several concepts showed similarity to existing measurement structures, whereas others differed. Conceptual similarity (convergence; eg, concepts in the care outcomes domain of functional level and harm-free care) provides further support of the critical foundational work in LTC measurement endorsed and implemented by regulatory bodies. Different concepts (divergence; eg, concepts in the person-centered care domain of knowing the person and what matters most to the person) highlights current gaps in measurement efforts and is consistent with WE-THRIVE's focus on supporting resilience and thriving for residents, family, and staff. In alignment with the World Health Organization's call for comparative measurement work for health systems change, WE-THRIVE's work to date highlights the benefits of engaging with diverse LTC researchers, including those in low-, middle-, and high-income countries, to develop a measurement infrastructure that integrates the aspirations of person-centered LTC.
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