High-resolution analyses of associations between medications, microbiome and mortality in cancer patients

Supplementary data files for a study investigating the associations between medication, microbiome and mortality in cancer patients. <br> <strong>Summary</strong> Discerning the effect of pharmacological exposures on intestinal bacterial communities in cancer patients is challenging. Here, we deconvoluted the relationship between drug exposures and changes in microbial composition by developing and applying a new computational method, PARADIGM (PARameters Associated with DynamIcs of Gut Microbiota), to a large set of longitudinal fecal microbiome profiles with detailed medication-administration records from patients undergoing allogeneic hematopoietic cell transplantation. We observed that several non-antibiotic drugs, including laxatives, antiemetics, and opioids, are associated with increased <em>Enterococcus</em> relative abundance and decreased alpha-diversity. Shotgun metagenomic sequencing further demonstrated subspecies competition, leading to increased dominant strain genetic convergence during allo-HCT that is significantly associated with antibiotic exposures. We integrated drug-microbiome associations to predict clinical outcomes in two validation cohorts on the basis of drug exposures alone, suggesting that this approach can generate biologically and clinically relevant insights on how pharmacological exposures can perturb or preserve microbiota composition.