Combinatorial, additive and dose-dependent drug–microbiome associations

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, L., 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., Amouyal, C., Andersson Galijatovic, E.A., Andreelli, F., Barthelemy, O., Batisse, J.-P., Belda, E., Berland, M., Bittar, R., Blottière, H., Bosquet, F., Boubrit, R., Bourron, O., Camus, M., Cassuto, D., Ciangura, C., Collet, J.-P., Dao, M.-C., Djebbar, M., Doré, A., Engelbrechtsen, L., Fellahi, S., Fromentin, S., Galan, P., Gauguier, D., Giral, P., Hartemann, A., Hartmann, B., Holst, J.J., Hornbak, M., Hoyles, L., Hulot, J.-S., Jaqueminet, S., Jørgensen, N.R., Julienne, H., Justesen, J., Kammer, J., Krarup, N., Kerneis, M., Khemis, J., Kozlowski, R., Lejard, V., Levenez, F., Lucas-Martini, L., Massey, R., Martinez-Gili, L., Maziers, N., Medina-Stamminger, J., Montalescot, G., Moute, S., Neves, A.L., Olanipekun, M., Le Pavin, L.P., Poitou, C., Pousset, F., Pouzoulet, L., Rodriguez-Martinez, A., Rouault, C., Silvain, J., Svendstrup, M., Swartz, T., Vanduyvenboden, T., Vatier, C., Walther, S., 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. and The MetaCardis Consortium (Hoyles, L.), ORCID: 0000-0002-6418-342X, 2021. Combinatorial, additive and dose-dependent drug–microbiome associations. Nature. ISSN 0028-0836

[img]
Preview
Text
1502891_Hoyles.pdf - Published version

Download (9MB) | Preview

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.

Item Type: Journal article
Publication Title: Nature
Creators: 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, L., 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., Amouyal, C., Andersson Galijatovic, E.A., Andreelli, F., Barthelemy, O., Batisse, J.-P., Belda, E., Berland, M., Bittar, R., Blottière, H., Bosquet, F., Boubrit, R., Bourron, O., Camus, M., Cassuto, D., Ciangura, C., Collet, J.-P., Dao, M.-C., Djebbar, M., Doré, A., Engelbrechtsen, L., Fellahi, S., Fromentin, S., Galan, P., Gauguier, D., Giral, P., Hartemann, A., Hartmann, B., Holst, J.J., Hornbak, M., Hoyles, L., Hulot, J.-S., Jaqueminet, S., Jørgensen, N.R., Julienne, H., Justesen, J., Kammer, J., Krarup, N., Kerneis, M., Khemis, J., Kozlowski, R., Lejard, V., Levenez, F., Lucas-Martini, L., Massey, R., Martinez-Gili, L., Maziers, N., Medina-Stamminger, J., Montalescot, G., Moute, S., Neves, A.L., Olanipekun, M., Le Pavin, L.P., Poitou, C., Pousset, F., Pouzoulet, L., Rodriguez-Martinez, A., Rouault, C., Silvain, J., Svendstrup, M., Swartz, T., Vanduyvenboden, T., Vatier, C., Walther, S., 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. and The MetaCardis Consortium (Hoyles, L.),
Publisher: Springer
Date: 8 December 2021
ISSN: 0028-0836
Identifiers:
NumberType
10.1038/s41586-021-04177-9DOI
1502891Other
Rights: The article is made available under a Creative Commons CC-BY license, which allows for anyone to reuse, share, or build upon the work.
Divisions: Schools > School of Science and Technology
Record created by: Jonathan Gallacher
Date Added: 14 Dec 2021 09:39
Last Modified: 14 Dec 2021 13:22
URI: http://irep.ntu.ac.uk/id/eprint/45119

Actions (login required)

Edit View Edit View

Views

Views per month over past year

Downloads

Downloads per month over past year