AGORA2: Large scale reconstruction of the microbiome highlights wide-spread drug-metabolising capacities

The human microbiome influences the efficacy and safety of a wide variety of commonly prescribed drugs, yet comprehensive systems-level approaches to interrogate drug-microbiome interactions are lacking. Here, we present a computational resource of human microbial genome-scale reconstructions, deemed AGORA2, which accounts for 7,206 strains, includes microbial drug degradation and biotransformation, and was extensively curated based on comparative genomics and literature searches. AGORA2 serves as a knowledge base for the human microbiome and as a metabolic modelling resource. We demonstrate the latter by mechanistically modelling microbial drug metabolism capabilities in single strains and pairwise models. Moreover, we predict the individual-specific drug conversion potential in a cohort of 616 colorectal cancer patients and controls. This analysis reveals that some drug activation capabilities are present in only a subset of individuals, moreover, drug conversion potential correlate with clinical parameters. Thus, AGORA2 paves the way towards personalised, predictive analysis of host-drug-microbiome interactions.