RapidAIM: a culture- and metaproteomics-based Rapid Assay of Individual Microbiome responses to drugs
Abstract
BACKGROUND: Human-targeted drugs may exert off-target effects or can be repurposed to modulate the gut microbiota. However, our understanding of such effects is limited due to a lack of rapid and scalable assay to comprehensively assess microbiome responses to drugs. Drugs and other compounds can drastically change the overall abundance, taxonomic composition, and functions of a gut microbiome.
RESULTS: Here, we developed an approach to screen compounds against individual microbiomes in vitro, using metaproteomics to both measure absolute bacterial abundances and to functionally profile the microbiome. Our approach was evaluated by testing 43 compounds (including 4 antibiotics) against 5 individual microbiomes. The method generated technically highly reproducible readouts, including changes of overall microbiome abundance, microbiome composition, and functional pathways. Results show that besides the antibiotics, the compounds berberine and ibuprofen inhibited the accumulation of biomass during in vitro growth of the microbiota. By comparing genus and species level-biomass contributions, selective antibacterial-like activities were found with 35 of the 39 non-antibiotic compounds. Seven of the compounds led to a global alteration of the metaproteome, with apparent compound-specific patterns of functional responses. The taxonomic distributions of altered proteins varied among drugs, i.e., different drugs affect functions of different members of the microbiome. We also showed…
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