@article{fdi:010083829,
  title = {{C}ombinatorial, additive and dose-dependent drug-microbiome associations},
  author = {{F}orslund, {S}. {K}. and {C}hakaroun, {R}. and {Z}immermann-{K}ogadeeva, {M}. and {M}arko, {L}. and {A}ron-{W}isnewsky, {J}. and {N}ielsen, {T}. and {M}oitinho-{S}ilva, {L}. and {S}chmidt, {T}. {S}. {B}. and {F}alony, {G}. and {V}ieira-{S}ilva, {S}. and {A}driouch, {S}. and {A}lves, {R}. {J}. and {A}ssmann, {K}. and {B}astard, {J}. {P}. and {B}irkner, {T}. and {C}aesar, {R}. and {C}hilloux, {J}. and {C}oelho, {L}. {P}. and {F}ezeu, {L}. and {G}alleron, {N}. and {H}elft, {G}. and {I}snard, {R}. and {J}i, {B}. {Y}. and {K}uhn, {M}. and {L}e {C}hatelier, {E}. and {M}yridakis, {A}. and {O}lsson, {L}. and {P}ons, {N}. and {P}rifti, {E}di and {Q}uinquis, {B}. and {R}oume, {H}. and {S}alem, {J}. {E}. and {S}okolovska, {N}. and {T}remaroli, {V}. and {V}alles-{C}olomer, {M}. and {L}ewinter, {C}. and {S}ondertoft, {N}. {B}. and {P}edersen, {H}. {K}. and {H}ansen, {T}. {H}. and {G}otze, {J}. {P}. and {K}ober, {L}. and {V}estergaard, {H}. and {H}ansen, {T}. and {Z}ucker, {J}ean-{D}aniel and {H}ercberg, {S}. and {O}ppert, {J}. {M}. and {L}etunic, {I}. and {N}ielsen, {J}. and {B}ackhed, {F}. and {E}hrlich, {S}. {D}. and {D}umas, {M}. {E}. and {R}aes, {J}. and {P}edersen, {O}. and {C}lement, {K}. and {S}tumvoll, {M}. and {B}ork, {P}. and {M}eta{C}ardis {C}onsortium},
  editor = {},
  language = {{ENG}},
  abstract = {{D}uring 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(1-5). {H}ere, through integrated multi-omics analyses of 2,173 {E}uropean residents from the {M}eta{C}ardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. {W}e 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 {R}oseburia by diuretic agents combined with beta-blockers. {S}everal 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. {W}e also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. {T}aken 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. {F}urthermore, the robust signatures identified using our framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease.},
  keywords = {{EUROPE}},
  booktitle = {},
  journal = {{N}ature},
  volume = {600},
  numero = {},
  pages = {500--505 + [15 ]},
  ISSN = {0028-0836},
  year = {2021},
  DOI = {10.1038/s41586-021-04177-9},
  URL = {https://www.documentation.ird.fr/hor/fdi:010083829},
}