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ToolsLi, Leyuan, Simopoulos, Caitlin M.A., Mayne, Janice, Ning, Zhibin, Zhang, Xin, Hamada, Mona, Butcher, James, Serrana, Joeselle M., Wang, Luman, Cheng, Kai, Qin, Hongye, Walker, Krystal, Zhang, Xu, Stintzi, Alain and Figeys, Daniel (2025) Systematic metaproteomics mapping reveals functional and ecological landscapes of Ex vivo human gut microbiota responses to therapeutic drugs. Nature Communications, 16 (1). ISSN 2041-1723
Full text not available from this repository. (Request a copy)Abstract
Therapeutic compounds exert impacts on gut microbiota; however, how they affect the community functional ecology, especially as reflected at the protein level, remains largely unexplored. In this study, we systematically map metaproteomic responses of ex vivo human gut microbiota to 312 compounds, generating 4.6 million microbial protein responses, available as an interactive resource (https://shiny.imetalab.ca/MPR_Viz/). Protein-level analyses identify significant metaproteomic shifts induced by 47 compounds, with neuropharmaceuticals as the sole drug class significantly enriched among these hits. Further analyses on the community level reveal a tri-stability pattern in microbial composition and the emergence of three distinct functional states, based on a functional beta-diversity metric. Notably, neuropharmaceuticals cause particularly strong effects on the microbiomes, lowering the proteome-level functional redundancy and raising the level of antimicrobial resistance proteins, ultimately pushing the microbiome into an alternative functional state. Preliminary validation suggests that enhancing functional redundancy may contribute to maintaining microbiota resilience against neuropharmaceutical-induced antimicrobial resistance. Overall, this work establishes a comprehensive view of how drugs influence gut microbiome function and ecology at the protein level, proposes a landscape-based framework for interpreting community resilience, and highlights the need to consider protein-level and ecological responses in the evaluation of therapeutic interventions.
| Item Type: | Article |
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| Additional Information: | Data availability: All metaproteomics data sets reported in this study have been deposited in the ProteomeXchange database through the PRIDE repository under accession codes PXD056930, PXD056888, PXD056968. The metagenomics data used in this study are deposited in the NCBI Sequence Read Archive (SRA) with the accession numbers SRR30894461, SRR30894462, SRR30894463, SRR30894464, SRR30894465 and SRR29021656. Source data are provided in this paper. Code availability: Code and related data to reproduce the analyses in this study has been published in figshare through https://doi.org/10.6084/m9.figshare.29816780. In addition, the source code of the Shiny app is made publicly available via GitHub at https://github.com/yvonnelee1988/MPR_Viz and Zendo at https://doi.org/10.5281/zenodo.16990829. Any additional information required to reanalyze the data reported in this paper is available from the lead contact (Daniel Figeys, Daniel.Figeys@quadram.ac.uk) upon request. |
| Uncontrolled Keywords: | chemistry(all),biochemistry, genetics and molecular biology(all),general,physics and astronomy(all) ,/dk/atira/pure/subjectarea/asjc/1600 |
| 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: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 27 Mar 2026 12:30 |
| Last Modified: | 29 Mar 2026 06:34 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/102614 |
| DOI: | 10.1038/s41467-025-64433-8 |
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