Combinatorial, additive and dose-dependent drug–microbiome associations - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Nature Année : 2021

Combinatorial, additive and dose-dependent drug–microbiome associations

1 EMBL - European Molecular Biology Laboratory [Heidelberg]
2 MDC - Max Delbrück Center for Molecular Medicine [Berlin]
3 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
4 BIH - Berlin Institute of Health
5 DZHK - German Center for Cardiovascular Research
6 Leipzig University / Universität Leipzig
7 Nutriomics - Nutrition et obésités: approches systémiques (UMR-S 1269)
8 CHU Pitié-Salpêtrière [AP-HP]
9 UCPH - University of Copenhagen = Københavns Universitet
10 UNSW - University of New South Wales [Sydney]
11 PSI - Paul Scherrer Institute
12 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
13 Universität Heidelberg [Heidelberg] = Heidelberg University
14 EREN [CRESS - U1153 / UMR_A 1125] - Nutritional Epidemiology Research Team | Equipe de Recherche en Epidémiologie Nutritionnelle
15 CRSA - Centre de Recherche Saint-Antoine
16 CHU Henri Mondor [Créteil]
17 ICAN - Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases
18 GU - Göteborgs Universitet = University of Gothenburg
19 Imperial College London
20 MGP (US 1367) - MetaGenoPolis
21 Université Paris-Saclay
22 Institut de cardiologie [CHU Pitié-Salpêtrière]
23 Chalmers University of Technology [Gothenburg, Sweden]
24 UMMISCO - Unité de modélisation mathématique et informatique des systèmes complexes [Bondy]
25 CIC Paris-Est - Centre d'investigation clinique Paris Est [CHU Pitié Salpêtrière]
26 CRESS (U1153 / UMR_A 1125) - Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques
27 BS - Biobyte Solutions [Heidelberg, Germany]
28 ITU - IT University of Copenhagen
29 Sahlgrenska University Hospital [Gothenburg]
30 EGENODIA (GI3M) - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
31 NHLI - National Heart and Lung Institute [London]
32 McGill University and Genome Quebec Innovation Centre
33 HIU - Helmholtz Institute Ulm
34 Helmholtz Zentrum München = German Research Center for Environmental Health
35 JMU - Julius-Maximilians-Universität Würzburg
36 Yonsei University
Julien Chilloux
Antonis Myridakis
Nicolas Pons
  • Fonction : Auteur
Benoit Quinquis
  • Fonction : Auteur
Hugo Roume
  • Fonction : Auteur
S. Dusko Ehrlich
Oluf Pedersen

Résumé

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.
Fichier principal
Vignette du fichier
2021_Forslund_Nature.pdf (9.39 Mo) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

hal-03873160 , version 1 (16-03-2023)

Identifiants

Citer

Sofia Forslund, Rima Chakaroun, Maria Zimmermann-Kogadeeva, Lajos Markó, Judith Aron-Wisnewsky, et al.. Combinatorial, additive and dose-dependent drug–microbiome associations. Nature, 2021, 600 (7889), pp.500-505. ⟨10.1038/s41586-021-04177-9⟩. ⟨hal-03873160⟩
137 Consultations
310 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More