PR002566 (Project)

Description:Human gut bacteria are routinely exposed to stresses, and collateral effects are difficult to predict. To interrogate community-level responses to perturbations, we screened stool-derived in vitro communities with 707 clinically relevant drugs, and anlyzed the exometabolomics data of the resulting communities along with their growth and compositional changes. Drug bioaccumulation and degradation are rare. Compositional and metabolomic responses were predictably impacted by nutrient competition, and each bacterial species in the community maintains most of its nutrient niche. Finally, in defined, simplified communities, the response to drug perturbations of each species are quantitatively predicted from their drug susceptibility and metabolic profiles. Our study reveals that quantitative understanding of the interaction landscape, particularly nutrient competition, can be used to anticipate and potentially mitigate side effects of drug treatment on the gut microbiota.