| 1. |
- Vieira-Silva, S., et al.
(författare)
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Statin therapy is associated with lower prevalence of gut microbiota dysbiosis
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 581:7808, s. 310-315
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Tidskriftsartikel (refereegranskat)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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| 2. |
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| 3. |
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| 4. |
- 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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| 5. |
- 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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| 6. |
- Hue, V, et al.
(författare)
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Juno-UVS Observation of the Io Footprint During Solar Eclipse
- 2019
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Ingår i: Journal of Geophysical Research - Space Physics. - : AMER GEOPHYSICAL UNION. - 2169-9380 .- 2169-9402. ; 124:7, s. 5184-5199
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Tidskriftsartikel (refereegranskat)abstract
- The two main ultraviolet-signatures resulting from the Io-magnetosphere interaction are the local auroras on Io's atmosphere, and the Io footprints on Jupiter. We study here how Io's daily eclipses affect the footprint. Previous observations showed that its atmosphere collapses in eclipse. While remote observers can observe Io's local auroras briefly when Io disappears behind Jupiter, Juno is able to follow the Io footprint in the unlit hemisphere. Theoretical models of the variability of the energy flux fed into the Alfven wings, ultimately powering the footprints, are not sufficiently constrained by observations. For the first time, we use observations of Io's footprint from the Ultraviolet Spectrograph (UVS) on Juno recorded as Io went into eclipse. We benchmark the trend of the footprint brightness using observations by UVS taken over Io's complete orbit and find that the footprint emitted power variation with Jupiter's rotation shows fairly consistent trends with previous observations. Two exploitable data sets provided measurements when Io was simultaneously in eclipse. No statistically significant changes were recorded as Io left and moved into eclipse, respectively, suggesting either that (i) Io's atmospheric densities within and outside eclipse are large enough to produce a saturated plasma interaction, that is, in the saturated state, changes in Io's atmospheric properties to first order do not control the total Alfvenic energy flux, (ii) the atmospheric collapse during the Juno observations was less than previously observed, or (iii) additional processes of the Alfven wings in addition to the Poynting flux generated at Io control the footprint luminosity.
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| 7. |
- 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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| 8. |
- Aumüller, G., et al.
(författare)
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Species‐ and organ‐specificity of secretory proteins derived from human prostate and seminal vesicles
- 1990
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Ingår i: The Prostate. - : Wiley. - 0270-4137 .- 1097-0045. ; 17:1, s. 31-40
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Tidskriftsartikel (refereegranskat)abstract
- Polyclonal antibodies against semenogelin (SG) isolated from human seminal vesicle secretion and acid phosphatase (PAP), β‐microseminoprotein (β‐MSP), and Prostate‐Specific Antigen (PSA) derived from human prostatic fluid, as well as a monoclonal antibody against β‐MSP were used for immunocytochemical detection of the respective antigens in different organs from different species. SG immunoreactivity was detected in the epithelium of the pubertal and adult human and in monkey seminal vesicle, ampulla of the vas deferens, and ejaculatory duct. PAP, β‐MSP, and PSA immunoreactivities were detected in the pubertal and adult human prostate and the cranial and caudal monkey prostate. With the exception of a weak PSA immunoreactivity in the proximal portions of the ejaculatory duct, none of the latter antisera reacted with seminal vesicle, ampullary, and ejaculatory duct epithelium. Among the non‐primate species studied (dog, bull, rat, guinea pig) only the canine prostatic epithelium displayed a definite immunoreactivity with the PAP antibody and a moderate reaction with the PSA antibody. No immunoreaction was seen in bull and rat seminal vesicle and canine ampulla of the vas deferens with the SG antibody. The same was true for the (ventral) prostate of rat, bull, and dog for β‐MSP. The epithelium of the rat dorsal prostate showed a slight cross‐reactivity with the monoclonal antibody against β‐MSP and one polyclonal antibody against PSA. The findings indicate a rather strict species‐dependent expression of human seminal proteins which show some similarities in primates, but only marginal relationship to species with different physiology of seminal fluid.
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| 9. |
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| 10. |
- Kaegi, R., et al.
(författare)
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Release of TiO2 – (Nano) particles from construction and demolition landfills
- 2017
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Ingår i: NanoImpact. - : Elsevier BV. - 2452-0748. ; 8, s. 73-79
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Tidskriftsartikel (refereegranskat)abstract
- A large fraction of engineered nanomaterials (ENM) will be deposited in landfills and it is assumed that ENM are securely locked in landfill sites and cannot leach into the environment (e.g. surface waters). However, experimental evidence supporting this assumption is lacking, as current production volumes of ENM are still too small and/or analytical techniques not sensitive enough to allow for the detection and quantification of ENM in landfill leachates. TiO2 particles are currently used in large quantities, for example in construction materials such as paints and renders as white pigments and their sizes extend into the nano-size range. We, therefore, selected TiO2 particles as a surrogate to assess the potential release of ENM from construction and demolition (C&D) landfill sites. We collected leachate samples from a landfill over one year and used complementary analytical techniques, including inductively coupled plasma (ICP) – optical emission spectroscopy (OES), automated scanning electron microscopy (auto SEM), transmission electron microscopy (TEM) and single particle ICP - mass spectrometry (spICPMS) to quantify TiO2 particles in landfill leachates. Total elemental Ti contents were mostly around a few tens of μg L− 1 and were strongly correlated with total suspended solids. Based on the volumetric discharge of the landfill leachate water from the landfill, we estimate a total amount of ~ 0.5 kg of TiO2 particles that are released annually from the landfill. Ti concentrations derived from ICP-OES measurements were in good agreement with quantifications based on TiO2 particles detected by auto SEM analyses. spICPMS measurements indicated a number concentration of Ti-containing particles in the order of 105 mL− 1 and TEM analyses dominantly revealed nanoscale TiO2 particles with a spherical shape typically observed for TiO2 particles used as white pigments. In addition, angular TiO2 particles with a well-defined crystal habitus were detected, suggesting that also natural TiO2 particles of comparable sizes are present in the landfill leachates. The results from this study indicate that (nanoscale) TiO2 particles are released from C&D landfill sites (~ 5 g/year). Although the amount of TiO2 particles released from C&D landfill sites may still be rather low, these particles may serve as proxy for assessing the future release of ENM from C&D landfill sites, which may become relevant as an increasing use of ENM is predicted for construction materials in general. © 2017 Elsevier B.V.
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| 11. |
- Micic, V., et al.
(författare)
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Impact of Sodium Humate Coating on Collector Surfaces on Deposition of Polymer-Coated Nanoiron Particles
- 2017
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Ingår i: Environmental Science & Technology. - : American Chemical Society (ACS). - 0013-936X .- 1520-5851. ; 51:16, s. 9202-9209
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Tidskriftsartikel (refereegranskat)abstract
- The affinity between nanoscale zerovalent iron (nano-ZVI) and mineral surfaces hinders its mobility, and hence its delivery into contaminated aquifers. We have tested the hypothesis that the attachment of poly(acrylic acid)-coated nano-ZVI (PAA-nano-ZVI) to mineral surfaces could be limited by coating such surfaces with sodium (Na) humate prior to PAA-nano-ZVI injection. Na humate was expected to form a coating over favorable sites for PAA-nano-ZVI attachment and hence reduce the affinity of PAA-nano-ZVI for the collector surfaces through electrosteric repulsion between the two interpenetrating charged polymers. Column experiments demonstrated that a low concentration (10 mg/L) Na humate solution in synthetic water significantly improved the mobility of PAA-nano-ZVI within a standard sand medium. This effect was, however, reduced in more heterogeneous natural collector media from contaminated sites, as not an adequate of the collector sites favorable for PAA-nano-ZVI attachment within these media appear to have been screened by the Na humate. Na humate did not interact with the surfaces of acid-washed glass beads or standard Ottawa sand, which presented less surface heterogeneity. Important factors influencing the effectiveness of Na humate application in improving PAA-nano-ZVI mobility include the solution chemistry, the Na humate concentration, and the collector properties.
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| 12. |
- Nowack, Bernd, et al.
(författare)
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Progress towards the validation of modeled environmental concentrations of engineered nanomaterials by analytical measurements
- 2015
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Ingår i: Environmental Science: Nano. - 2051-8153. ; 2:5, s. 421-428
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Tidskriftsartikel (refereegranskat)abstract
- Environmental exposure modeling has been used extensively in the last years to obtain estimates of environmental concentrations of engineered nanomaterials (ENMs). In this perspective piece, we explore the issues when aiming to validate modeled environmental concentrations and propose options for both modelers and analytical chemists on how to proceed in the future to better compliment one another's efforts. In this context, validation means to determine the degree to which the simulation results from a model are accurate representations of the real world by comparison with analytical data. Therefore, for such a model validation procedure, analytical methods need to be available which provide information in the same subject area. Currently, a major issue with nanometrology is that a multitude of nanomaterials are present in natural systems but only some are ENMs; various other particles of natural origin are abundant in the same systems. The analytical tools available are not yet capable to distinguish the natural from engineered nanomaterials at the low ENM concentrations expected in complex environmental matrices. However, both modeling and analytical studies are able to provide an orthogonal view on nanomaterials: modeling is able to yield estimates of the presence of ENMs in various environmental compartments while analytics can provide physical characterization of ENMs in these systems with hints towards the total nanomaterial concentration. While we need to make strides to improve the two approaches separately, using the resulting data together in a mutually supportive way will advance the field of ENM risk assessment.
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| 13. |
- Praetorius, A., et al.
(författare)
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Single-particle multi-element fingerprinting (spMEF) using inductively-coupled plasma time-of-flight mass spectrometry (ICP-TOFMS) to identify engineered nanoparticles against the elevated natural background in soils
- 2017
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Ingår i: Environmental Science: Nano. - : Royal Society of Chemistry (RSC). - 2051-8153 .- 2051-8161. ; 4:2, s. 307-314
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Tidskriftsartikel (refereegranskat)abstract
- The discrimination of engineered nanoparticles (ENPs) from the natural geogenic background is one of the preeminent challenges for assessing their potential implications. At low ENP concentrations, most conventional analytical techniques are not able to take advantage of inherent differences (e.g. in terms of composition, isotopic signatures, element ratios, structure, shape or surface characteristics) between ENPs and naturally occurring nanoscale particles (NNPs) of similar composition. Here, we present a groundbreaking approach to overcome these limitations and enable the discrimination of man-made ENPs from NNPs through simultaneous detection of multiple elements on an individual particle level. This new analytical approach is accessible by an inductively-coupled plasma time-of-flight mass spectrometer (ICP-TOFMS) operated in single-particle mode. Machine learning is employed to classify ENPs and NNPs based on their unique elemental fingerprints and quantify their concentrations. We demonstrate the applicability of this single-particle multi-element fingerprinting (spMEF) method by distinguishing engineered cerium oxide nanoparticles (CeO2 ENPs) from natural Ce-containing nanoparticles (Ce-NNPs) in soils at environmentally relevant ENP concentrations, orders of magnitude below the natural background.
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| 14. |
- Praetorius, A., et al.
(författare)
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Strategies for determining heteroaggregation attachment efficiencies of engineered nanoparticles in aquatic environments
- 2020
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Ingår i: Environmental Science-Nano. - : Royal Society of Chemistry (RSC). - 2051-8153 .- 2051-8161. ; 7:2, s. 351-367
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Tidskriftsartikel (refereegranskat)abstract
- Heteroaggregation of engineered nanoparticles (ENPs) with suspended particulate matter (SPM) ubiquitous in natural waters often dominates the transport behaviour and overall fate of ENPs in aquatic environments. In order to provide meaningful exposure predictions and support risk assessment for ENPs, environmental fate and transport models require quantitative information about this process, typically in the form of the so-called attachment efficiency for heteroaggregation alpha(hetero). The inherent complexity of heteroaggregation-encompassing at least two different particle populations, various aggregation pathways and several possible attachment efficiencies (alpha values)-makes its theoretical and experimental determination challenging. In this frontier review we assess the current state of knowledge on heteroaggregation of ENPs with a focus on natural surface waters. A theoretical analysis presents relevant equations, outlines the possible aggregation pathways and highlights different types of alpha. In a second part, experimental approaches to study heteroaggregation and derive alpha values are reviewed and three possible strategies are identified: i) monitoring changes in size, ii) monitoring number or mass distribution and iii) studying indirect effects, such as sedimentation. It becomes apparent that the complexity of heteroaggregation creates various challenges and no single best method for its assessment has been developed yet. Nevertheless, many promising strategies have been identified and meaningful data can be derived from carefully designed experiments when accounting for the different concurrent aggregation pathways and clearly stating the type of alpha reported. For future method development a closer connection between experiments and models is encouraged.
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| 15. |
- Tharaud, M., et al.
(författare)
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TiO2 nanomaterial detection in calcium rich matrices by spICPMS. A matter of resolution and treatment
- 2017
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Ingår i: Journal of Analytical Atomic Spectrometry. - : Royal Society of Chemistry (RSC). - 0267-9477 .- 1364-5544. ; 32:7, s. 1400-1411
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Tidskriftsartikel (refereegranskat)abstract
- High Ca concentrations in complex matrices such as river waters often hamper the detection of titanium nanomaterials (TiO2 NPs) by single particle inductively coupled plasma mass spectrometry (spICPMS), because of isobaric interference of Ca-48 on the most abundant Ti isotope (Ti-48). Several approaches were used to reduce this interference while measuring TiO2 in solutions with different Ca concentrations up to 100 mg L-1. ICP-MS/MS was used with ammonia as the reaction ceLL gas and high resoLution (HR) ICP-MS was used under different resoLution settings. These approaches were compared by measuring different Ti isotopes (Ti-47 and Ti-49). spICPMS data were then treated with a deconvoLution method to filter out dissolved signals and identify the best approach to detect the Lowest possible corresponding spherical size of TiO2 NPs (D,in). ICP-MS/MS aLLowed for an important decrease of the theoretical D-min compared to standard quadrupole ICP-MS, down to 64 nm in uLtrapure water; however the sensitivity was reduced by the reaction gas and increasing Ca concentrations also increased the D-min. The comparably higher sensitivity of HR-ICP-MS aLLowed for theoretically measuring a D-min of 10 nm in uLtrapure water. Combined with the deconvoLution analysis, the highest resoLution mode in HR-ICP-MS Leads to the Lowest D-min at high Ca concentrations, even though significant broadening of the measured mass distributions occurred for TiO2 NPs at Ca concentrations up to 100 mg L-1.
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