Cited by 330Gut microbiota and healthMicrobial Community Ecology and PhysiologyOral microbiology and periodontitis research

RapidAIM: a culture- and metaproteomics-based Rapid Assay of Individual Microbiome responses to drugs

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Li, Leyuan, Ning, Zhibin, Zhang, Xu, Mayne, Janice, Cheng, Kai, Stintzi, Alain, Figeys, Daniel·2020·Microbiome

Published version of a preprint

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.

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Authors
Li, L., Ning, Z., Zhang, X., Mayne, J., Cheng, K., Stintzi, A., & Figeys, D.
Affiliations
  • University of Ottawa (CA)
  • Canadian Institute for Advanced Research (CA)
Corresponding author
  • Stintzi, Alain
  • Figeys, Daniel
Venue
Microbiome
Published
2020-03-11
Volume
8
Issue
1
Pages
33-33
ISSN
2049-2618 (ISSN-L)
OpenAlex
W3010746544
Cited by
328
References
78
Citations by year
2026: 28 · 2025: 60 · 2024: 60 · 2023: 60 · 2022: 53 · 2021: 49 · 2020: 14 · 2019: 3 · 2018: 1
FWCI
14.28
Type
journal article
Language
en
Open access
Locations
  • Microbiome (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UEA Digital Repository (University of East Anglia) (acceptedVersion)
  • uO Research (University of Ottawa) (submittedVersion, public-domain)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Genome Canada (OGI-114 and OGI-149)
  • Canadian Institutes of Health Research (ECD-144627)
  • Natural Sciences and Engineering Research Council of Canada (210034)
  • Ontario Ministry of Economic Development and Innovation (REG1-4450)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Physical Sciences › Environmental Science › Ecology › Microbial Community Ecology and Physiology
  • Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
Keywords
gut microbiota, drug-microbiome interactions, metaproteomics, antibiotic effects on microbiota, selective antibacterial activity, bacterial biomass, berberine, ibuprofen, drug repurposing, personalized drug screening
MeSH terms
Proof of Concept Study, Adult, Anti-Bacterial Agents, Bacteria, Nonprescription Drugs, Feces, Female, Humans, Male, RNA, Ribosomal, 16S, Colony Count, Microbial, Proteomics, Prescription Drugs, Microbiota

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