BibTex format
@article{Forslund:2021:10.1038/s41586-021-04177-9,
author = {Forslund, SK and Chakaroun, R and Zimmermann-Kogadeeva, M and Marko, L and Aron-Wisnewsky, J and Nielsen, T and Moitinho-Silva, L and Schmidt, TSB and Falony, G and Vieira-Silva, S and Adriouch, S and Alves, RJ and Assmann, K and Bastard, J-P and Birkner, T and Caesar, R and Chilloux, J and Coelho, LP 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 Sondertoft, NB and Pedersen, HK and Hansen, TH and Gotze, JP and Kober, 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 Backhed, F and Ehrlich, SD and Dumas, M-E and Raes, J and Pedersen, O and Clement, K and Stumvoll, M and Bork, P},
doi = {10.1038/s41586-021-04177-9},
journal = {Nature},
pages = {500--505},
title = {Combinatorial, additive and dose-dependent drug-microbiome associations},
url = {http://dx.doi.org/10.1038/s41586-021-04177-9},
volume = {600},
year = {2021}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - 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.
AU - Forslund,SK
AU - Chakaroun,R
AU - Zimmermann-Kogadeeva,M
AU - Marko,L
AU - Aron-Wisnewsky,J
AU - Nielsen,T
AU - Moitinho-Silva,L
AU - Schmidt,TSB
AU - Falony,G
AU - Vieira-Silva,S
AU - Adriouch,S
AU - Alves,RJ
AU - Assmann,K
AU - Bastard,J-P
AU - Birkner,T
AU - Caesar,R
AU - Chilloux,J
AU - Coelho,LP
AU - Fezeu,L
AU - Galleron,N
AU - Helft,G
AU - Isnard,R
AU - Ji,B
AU - Kuhn,M
AU - Le,Chatelier E
AU - Myridakis,A
AU - Olsson,L
AU - Pons,N
AU - Prifti,E
AU - Quinquis,B
AU - Roume,H
AU - Salem,J-E
AU - Sokolovska,N
AU - Tremaroli,V
AU - Valles-Colomer,M
AU - Lewinter,C
AU - Sondertoft,NB
AU - Pedersen,HK
AU - Hansen,TH
AU - Gotze,JP
AU - Kober,L
AU - Vestergaard,H
AU - Hansen,T
AU - Zucker,J-D
AU - Hercberg,S
AU - Oppert,J-M
AU - Letunic,I
AU - Nielsen,J
AU - Backhed,F
AU - Ehrlich,SD
AU - Dumas,M-E
AU - Raes,J
AU - Pedersen,O
AU - Clement,K
AU - Stumvoll,M
AU - Bork,P
DO - 10.1038/s41586-021-04177-9
EP - 505
PY - 2021///
SN - 0028-0836
SP - 500
TI - Combinatorial, additive and dose-dependent drug-microbiome associations
T2 - Nature
UR - http://dx.doi.org/10.1038/s41586-021-04177-9
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000728552800005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR - https://www.nature.com/articles/s41586-021-04177-9
VL - 600
ER -
