RapidAIM: A culture- And metaproteomics-based Rapid Assay of Individual Microbiome responses to drugs

Li, Leyuan, Ning, Zhibin, Zhang, Xu, Mayne, Janice, Cheng, Kai, Stintzi, Alain and Figeys, Daniel (2020) RapidAIM: A culture- And metaproteomics-based Rapid Assay of Individual Microbiome responses to drugs. Microbiome, 8 (1). pp. 1-16. ISSN 2049-2618

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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 that bacterial function can shift in response to drugs without a change in the abundance of the bacteria.  Conclusions: Current drug-microbiome interaction studies largely focus on relative microbiome composition and microbial drug metabolism. In contrast, our workflow enables multiple insights into microbiome absolute abundance and functional responses to drugs. The workflow is robust, reproducible, and quantitative and is scalable for personalized high-throughput drug screening applications.

Item Type:	Article
Additional Information:	Supplementary information accompanies this paper at https://doi.org/10. 1186/s40168-020-00806-z. All raw data from LC-MS/MS have been deposited to the ProteomeXchange Consortium (http://www.proteomexchange.org) via the PRIDE partner repository (dataset identifiers PXD012724 and PXD012725).
Uncontrolled Keywords:	absolute abundance,drug response,functional profile,gut microbiome,in vitro culturing,metaproteomics,microbiology,microbiology (medical) ,/dk/atira/pure/subjectarea/asjc/2400/2404
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	16 Mar 2026 13:30
Last Modified:	16 Mar 2026 14:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/102346
DOI:	10.1186/s40168-020-00806-z

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