Combinatorial, additive and dose-dependent drug–microbiome associations
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Combinatorial, additive and dose-dependent drug–microbiome associations. / Forslund, Sofia K.; Chakaroun, Rima; Zimmermann-Kogadeeva, Maria; Markó, Lajos; Aron-Wisnewsky, Judith; Nielsen, Trine; Moitinho-Silva, Lucas; Schmidt, Thomas S.B.; Falony, Gwen; Vieira-Silva, Sara; Adriouch, Solia; Alves, Renato J.; Assmann, Karen; Bastard, Jean Philippe; Birkner, Till; Caesar, Robert; Chilloux, Julien; Coelho, Luis Pedro; Fezeu, Leopold; Galleron, Nathalie; Helft, Gerard; Isnard, Richard; Ji, Boyang; Kuhn, Michael; Le Chatelier, Emmanuelle; Myridakis, Antonis; Olsson, Lisa; Pons, Nicolas; Prifti, Edi; Quinquis, Benoit; Roume, Hugo; Lewinter, Christian; Søndertoft, Nadja B.; Pedersen, Helle Krogh; Hansen, Tue H.; Hartmann, Bolette; Holst, Jens Juul; Hornbak, Malene; Jørgensen, Niklas Rye; Justesen, Johanne; Krarup, Nikolaj; Svendstrup, Mathilde; The MetaCardis Consortium*.
I: Nature, Bind 600, 2021, s. 500-517.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Combinatorial, additive and dose-dependent drug–microbiome associations
AU - Forslund, Sofia K.
AU - Chakaroun, Rima
AU - Zimmermann-Kogadeeva, Maria
AU - Markó, Lajos
AU - Aron-Wisnewsky, Judith
AU - Nielsen, Trine
AU - Moitinho-Silva, Lucas
AU - Schmidt, Thomas S.B.
AU - Falony, Gwen
AU - Vieira-Silva, Sara
AU - Adriouch, Solia
AU - Alves, Renato J.
AU - Assmann, Karen
AU - Bastard, Jean Philippe
AU - Birkner, Till
AU - Caesar, Robert
AU - Chilloux, Julien
AU - Coelho, Luis Pedro
AU - Fezeu, Leopold
AU - Galleron, Nathalie
AU - Helft, Gerard
AU - Isnard, Richard
AU - Ji, Boyang
AU - Kuhn, Michael
AU - Le Chatelier, Emmanuelle
AU - Myridakis, Antonis
AU - Olsson, Lisa
AU - Pons, Nicolas
AU - Prifti, Edi
AU - Quinquis, Benoit
AU - Roume, Hugo
AU - Lewinter, Christian
AU - Søndertoft, Nadja B.
AU - Pedersen, Helle Krogh
AU - Hansen, Tue H.
AU - Hartmann, Bolette
AU - Holst, Jens Juul
AU - Hornbak, Malene
AU - Jørgensen, Niklas Rye
AU - Justesen, Johanne
AU - Krarup, Nikolaj
AU - Svendstrup, Mathilde
AU - The MetaCardis Consortium
N1 - Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021
Y1 - 2021
N2 - 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.
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 discovery1–5. 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.
U2 - 10.1038/s41586-021-04177-9
DO - 10.1038/s41586-021-04177-9
M3 - Journal article
C2 - 34880489
AN - SCOPUS:85120973811
VL - 600
SP - 500
EP - 517
JO - Nature
JF - Nature
SN - 0028-0836
ER -
ID: 287612631