Helmholtz Gemeinschaft

Search
Browse
Statistics
Feeds

Combinatorial, additive and dose-dependent drug-microbiome associations

Item Type:Article
Title:Combinatorial, additive and dose-dependent drug-microbiome associations
Creators Name:Forslund, S.K. and Chakaroun, R. and Zimmermann-Kogadeeva, M. and Markó, L. and Aron-Wisnewsky, J. and Nielsen, T. and Moitinho-Silva, L. and Schmidt, T.S.B. and Falony, G. and Vieira-Silva, S. and Adriouch, S. and Alves, R.J. and Assmann, K. and Bastard, J.P. and Birkner, T. and Caesar, R. and Chilloux, J. and Coelho, L.P. and Fezeu, L. and Galleron, N. and Helft, G. and Isnard, R. and Ji, B. and Kuhn, M. and Le Chatelier, E. and Myridakis, A. and Olsson, L. and Pons, N. and Prifti, E. and Quinquis, B. and Roume, H. and Salem, J.E. and Sokolovska, N. and Tremaroli, V. and Valles-Colomer, M. and Lewinter, C. and Søndertoft, N.B. and Pedersen, H.K. and Hansen, T.H. and Gøtze, J.P. and Køber, L. and Vestergaard, H. and Hansen, T. and Zucker, J.D. and Hercberg, S. and Oppert, J.M. and Letunic, I. and Nielsen, J. and Bäckhed, F. and Ehrlich, S.D. and Dumas, M.E. and Raes, J. and Pedersen, O. and Clément, K. and Stumvoll, M. and Bork, P.
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 discovery. 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.
Keywords:Biomarkers, Cardiovascular Diseases, Systems Biology
Source:Nature
ISSN:0028-0836
Publisher:Nature Publishing Group
Volume:600
Page Range:500-505
Date:16 December 2021
Official Publication:http://doi.org/10.1038/s41586-021-04177-9
PubMed:View item in PubMed

Repository Staff Only: item control page

Open Access
MDC Library