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Forslund, S.K.* ; Chakaroun, R.* ; Zimmermann-Kogadeeva, M.* ; Markó, L.* ; Aron-Wisnewsky, J.* ; Nielsen, T.* ; Moitinho-Silva, L.* ; Schmidt, T.S.B.* ; Falony, G.* ; Vieira-Silva, S.* ; Adriouch, S.* ; Alves, R.J.* ; Assmann, K.* ; Bastard, J.P.* ; Birkner, T.* ; Caesar, R.* ; Chilloux, J.* ; Coelho, L.P.* ; Fezeu, F.* ; Galleron, N.* ; Helft, G.* ; Isnard, R.* ; Ji, B.* ; Kuhn, M.* ; Le Chatelier, E.* ; Myridakis, A.* ; Olsson, L.* ; Pons, N.* ; Prifti, E.* ; Quinquis, B.* ; Roume, H.* ; Salem, J.E.* ; Sokolovska, N.* ; Tremaroli, V.* ; Valles-Colomer, M.* ; Lewinter, C.* ; Søndertoft, N.B.* ; Pedersen, H.K.* ; Hansen, T.H.* ; Gøtze, J.P.* ; Køber, L.* ; Vestergaard, H.* ; Hansen, T.* ; Zucker, J.D.* ; Hercberg, S.* ; Oppert, J.M.* ; Letunic, I.* ; Nielsen, J.* ; Bäckhed, F.* ; Ehrlich, S.D.* ; Dumas, M.E.* ; Raes, J.* ; Pedersen, O.* ; Clément, K.* ; Stumvoll, M. ; Bork, P.*

Combinatorial, additive and dose-dependent drug-microbiome associations.

Nature 600, 500-505 (2021)
Postprint DOI PMC
Open Access Green
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Proton Pump Inhibitors; Human Gut Microbiome; American-college; Antibiotic Use; Task-force; Management; Guideline; Alters; Impact
Sprache englisch
Veröffentlichungsjahr 2021
HGF-Berichtsjahr 2021
ISSN (print) / ISBN 0028-0836
e-ISSN 1476-4687
Zeitschrift Nature
Quellenangaben Band: 600, Heft: 7889, Seiten: 500-505 Artikelnummer: , Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
POF Topic(s) 30201 - Metabolic Health
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-506500-001
Förderungen EMBL
H2020 European Research Council
Deutsche Forschungsgemeinschaft
NIHR Imperial Biomedical Research Centre
French National Research Agency
National Center for Precision Diabetic Medicine -PreciDIAB
French National Agency for Research
European Union (FEDER)
Hauts-de-France Regional Council
European Metropolis of Lille (MEL)
Novo Nordisk Foundation
Isite ULNE
ANR
European Union's Seventh Framework Program for research, technological development and demonstration
DOI 10.1038/s41586-021-04177-9
WOS ID WOS:000728552800005
WOS ID WOS:000730754700037
Scopus ID 85120973811
PubMed ID 34880489
Erfassungsdatum 2022-02-02
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