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DC Field | Value | Language |
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dc.contributor.author | Forslund, SK | - |
dc.contributor.author | Chakaroun, R | - |
dc.contributor.author | Zimmermann-Kogadeeva, M | - |
dc.contributor.author | Markó, L | - |
dc.contributor.author | Aron-Wisnewsky, J | - |
dc.contributor.author | Nielsen, T | - |
dc.contributor.author | Moitinho-Silva, L | - |
dc.contributor.author | Schmidt, TSB | - |
dc.contributor.author | Falony, G | - |
dc.contributor.author | Vieira-Silva, S | - |
dc.contributor.author | Adriouch, S | - |
dc.contributor.author | Alves, RJ | - |
dc.contributor.author | Assmann, K | - |
dc.contributor.author | Bastard, JP | - |
dc.contributor.author | Birkner, T | - |
dc.contributor.author | Caesar, R | - |
dc.contributor.author | Chilloux, J | - |
dc.contributor.author | Coelho, LP | - |
dc.contributor.author | Fezeu, L | - |
dc.contributor.author | Galleron, N | - |
dc.contributor.author | Helft, G | - |
dc.contributor.author | Isnard, R | - |
dc.contributor.author | Ji, B | - |
dc.contributor.author | Kuhn, M | - |
dc.contributor.author | Le Chatelier, E | - |
dc.contributor.author | Myridakis, A | - |
dc.contributor.author | Olsson, L | - |
dc.contributor.author | Pons, N | - |
dc.contributor.author | Prifti, E | - |
dc.contributor.author | Quinquis, B | - |
dc.contributor.author | Roume, H | - |
dc.contributor.author | Salem, JE | - |
dc.contributor.author | Sokolovska, N | - |
dc.contributor.author | Tremaroli, V | - |
dc.contributor.author | Valles-Colomer, M | - |
dc.contributor.author | Lewinter, C | - |
dc.contributor.author | Søndertoft, NB | - |
dc.contributor.author | Pedersen, HK | - |
dc.contributor.author | Hansen, TH | - |
dc.contributor.author | Amouyal, C | - |
dc.contributor.author | Andersson Galijatovic, EA | - |
dc.contributor.author | Andreelli, F | - |
dc.contributor.author | Barthelemy, O | - |
dc.contributor.author | Batisse, JP | - |
dc.contributor.author | Belda, E | - |
dc.contributor.author | Berland, M | - |
dc.contributor.author | Bittar, R | - |
dc.contributor.author | Blottière, H | - |
dc.contributor.author | Bosquet, F | - |
dc.contributor.author | Boubrit, R | - |
dc.contributor.author | Bourron, O | - |
dc.contributor.author | Camus, M | - |
dc.contributor.author | Cassuto, D | - |
dc.contributor.author | Ciangura, C | - |
dc.contributor.author | Collet, JP | - |
dc.contributor.author | Dao, MC | - |
dc.contributor.author | Djebbar, M | - |
dc.contributor.author | Doré, A | - |
dc.contributor.author | Engelbrechtsen, L | - |
dc.contributor.author | Fellahi, S | - |
dc.contributor.author | Fromentin, S | - |
dc.contributor.author | Galan, P | - |
dc.contributor.author | Gauguier, D | - |
dc.contributor.author | Giral, P | - |
dc.contributor.author | Hartemann, A | - |
dc.contributor.author | Hartmann, B | - |
dc.contributor.author | Holst, JJ | - |
dc.contributor.author | Hornbak, M | - |
dc.contributor.author | Hoyles, L | - |
dc.contributor.author | Hulot, JS | - |
dc.contributor.author | Jaqueminet, S | - |
dc.contributor.author | Jørgensen, NR | - |
dc.contributor.author | Julienne, H | - |
dc.contributor.author | Justesen, J | - |
dc.contributor.author | Kammer, J | - |
dc.contributor.author | Krarup, N | - |
dc.contributor.author | Kerneis, M | - |
dc.contributor.author | Khemis, J | - |
dc.contributor.author | Kozlowski, R | - |
dc.contributor.author | Lejard, V | - |
dc.contributor.author | Levenez, F | - |
dc.contributor.author | Lucas-Martini, L | - |
dc.contributor.author | Massey, R | - |
dc.contributor.author | Martinez-Gili, L | - |
dc.contributor.author | Maziers, N | - |
dc.contributor.author | Medina-Stamminger, J | - |
dc.contributor.author | Montalescot, G | - |
dc.contributor.author | Moute, S | - |
dc.contributor.author | Neves, AL | - |
dc.contributor.author | Olanipekun, M | - |
dc.contributor.author | Le Pavin, LP | - |
dc.contributor.author | Poitou, C | - |
dc.contributor.author | Pousset, F | - |
dc.contributor.author | Pouzoulet, L | - |
dc.contributor.author | Rodriguez-Martinez, A | - |
dc.contributor.author | Rouault, C | - |
dc.contributor.author | Silvain, J | - |
dc.contributor.author | Svendstrup, M | - |
dc.contributor.author | Swartz, T | - |
dc.contributor.author | Vanduyvenboden, T | - |
dc.contributor.other | The MetaCardis Consortium | - |
dc.date.accessioned | 2024-05-13T14:39:26Z | - |
dc.date.available | 2021-12-08 | - |
dc.date.available | 2024-05-13T14:39:26Z | - |
dc.date.issued | 2024-12-08 | - |
dc.identifier | ORCiD: Sofia K. Forslund https://orcid.org/0000-0003-4285-6993 | - |
dc.identifier | ORCiD: Antonis Myridakis https://orcid.org/0000-0003-1690-6651 | - |
dc.identifier | ORCiD: Karine Clément https://orcid.org/0000-0002-2489-3355 | - |
dc.identifier | ORCiD: Michael Stumvoll https://orcid.org/0000-0001-6225-8240 | - |
dc.identifier | ORCiD: Peer Bork https://orcid.org/0000-0002-2627-833X | - |
dc.identifier.citation | Forslund, S.K. et al. on behalf of The MetaCardis Consortium (2021) 'Combinatorial, additive and dose-dependent drug–microbiome associations', Nature, 600 (7889), pp. 500 - 505. doi: 10.1038/s41586-021-04177-9. | en_US |
dc.identifier.issn | 0028-0836 | - |
dc.identifier.uri | https://bura.brunel.ac.uk/handle/2438/28989 | - |
dc.description | Data availability: The source data for the figures are provided at Zenodo (https://doi.org/10.5281/zenodo.4728981). Raw shotgun sequencing data that support the findings of this study have been deposited at the ENA under accession codes PRJEB41311, PRJEB38742 and PRJEB37249 with public access. Raw spectra for metabolomics have been deposited in the MassIVE database under the accession codes MSV000088043 (UPLC–MS/MS) and MSV000088042 (GC–MS). The metadata on disease groups and drug intake are provided in Supplementary Tables 1–3. The demographic, clinical and phenotype metadata, and processed microbiome and metabolome data for French, German and Danish participants are available at Zenodo (https://doi.org/10.5281/zenodo.4674360). | en_US |
dc.description | Code availability: The new drug-aware univariate biomarker testing pipeline is available as an R package (metadeconfoundR; Birkner et al., manuscript in preparation) at Github (https://github.com/TillBirkner/metadeconfoundR) and at Zenodo (https://doi.org/10.5281/zenodo.4721078). The latest version (0.1.8) of this package was used to generate the data shown in this publication. The code used for multivariate analysis based on the VpThemAll package is available at Zenodo (https://doi.org/10.5281/zenodo.4719526). The phenotype and drug intake metadata, processed microbiome, and metabolome data and code resources are available for download at Zenodo (https://doi.org/10.5281/zenodo.4674360). The code for reproducing the figures is provided at Zenodo (https://doi.org/10.5281/zenodo.4728981). | - |
dc.description.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 discovery1,2,3,4,5. 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. | en_US |
dc.description.sponsorship | This work was supported by the European Union’s Seventh Framework Program for research, technological development and demonstration under grant agreement HEALTH-F4-2012-305312 (METACARDIS). Part of this work was also supported by the EMBL, by the Metagenopolis grant ANR-11-DPBS-0001, by the H2020 European Research Council (ERC-AdG-669830) (to P.B.), and by grants from the Deutsche Forschungsgemeinschaft (SFB1365 to S.K.F. and L.M.; and SFB1052/3 A1 MS to M.S. (209933838)). Assistance Publique-Hôpitaux de Paris is the promoter of the clinical investigation (MetaCardis). M.-E.D. is supported by the NIHR Imperial Biomedical Research Centre and by grants from the French National Research Agency (ANR-10-LABX-46 (European Genomics Institute for Diabetes)), from the National Center for Precision Diabetic Medicine – PreciDIAB, which is jointly supported by the French National Agency for Research (ANR-18-IBHU-0001), by the European Union (FEDER), by the Hauts-de-France Regional Council (Agreement 20001891/NP0025517) and by the European Metropolis of Lille (MEL, Agreement 2019_ESR_11) and by Isite ULNE (R-002-20-TALENT-DUMAS), also jointly funded by ANR (ANR-16-IDEX-0004-ULNE), the Hauts-de-France Regional Council (20002845) and by the European Metropolis of Lille (MEL). R.J.A. is a member of the Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Bioscience. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research institution at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation. | en_US |
dc.format.extent | 500 - 505 | - |
dc.format.medium | Print-Electronic | - |
dc.language | English | - |
dc.language.iso | en_US | en_US |
dc.publisher | Springer Nature | en_US |
dc.relation.uri | https://doi.org/10.5281/zenodo.4728981 | - |
dc.relation.uri | https://www.ebi.ac.uk/ena/data/view/PRJEB41311 | - |
dc.relation.uri | https://www.ebi.ac.uk/ena/data/view/PRJEB38742 | - |
dc.relation.uri | https://www.ebi.ac.uk/ena/data/view/PRJEB37249 | - |
dc.relation.uri | https://massive.ucsd.edu/ProteoSAFe/QueryMSV?id=MSV000088043 | - |
dc.relation.uri | https://massive.ucsd.edu/ProteoSAFe/QueryMSV?id=MSV000088042 | - |
dc.relation.uri | https://doi.org/10.5281/zenodo.4674360 | - |
dc.relation.uri | https://github.com/TillBirkner/metadeconfoundR | - |
dc.relation.uri | https://doi.org/10.5281/zenodo.4721078 | - |
dc.relation.uri | https://doi.org/10.5281/zenodo.4719526 | - |
dc.relation.uri | https://doi.org/10.5281/zenodo.4674360 | - |
dc.relation.uri | https://doi.org/10.5281/zenodo.4728981 | - |
dc.rights | Copyright © 20221 Springer Nature. This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1038/s41586-021-04177-9 (see: https://www.springernature.com/gp/open-research/policies/journal-policies). | - |
dc.rights.uri | https://www.springernature.com/gp/open-research/policies/journal-policies | - |
dc.subject | biomarkers | en_US |
dc.subject | cardiovascular diseases | en_US |
dc.subject | systems biology | en_US |
dc.title | Combinatorial, additive and dose-dependent drug–microbiome associations | en_US |
dc.type | Article | en_US |
dc.identifier.doi | https://doi.org/10.1038/s41586-021-04177-9 | - |
dc.relation.isPartOf | Nature | - |
pubs.issue | 7889 | - |
pubs.publication-status | Published | - |
pubs.volume | 600 | - |
dc.identifier.eissn | 1476-4687 | - |
dc.rights.holder | Springer Nature | - |
Appears in Collections: | Dept of Life Sciences Research Papers |
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FullText.pdf | Copyright © 20221 Springer Nature. This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1038/s41586-021-04177-9 (see: https://www.springernature.com/gp/open-research/policies/journal-policies). | 5.04 MB | Adobe PDF | View/Open |
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