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, the researchers show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. They quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shifts the metabolome and microbiome towards a healthier state. Different relationships between antibiotics, cardiometabolic drug dosage, improvement in clinical markers and microbiome composition are presented. Taken together, this 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 this framework provide new hypotheses for drug-host-microbiome interactions in cardiometabolic disease.
Combinatorial, additive and dose-dependent drug–microbiome associations
Peer Bork(1), Karine Clément(2), Michael Stumvoll(3)
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