Ultra-sensitive metaproteomics redefines the dark metaproteome, uncovering host-microbiome interactions and drug targets in intestinal diseases

Feng Xian, Malena Brenek, Christoph Krisp, Elisabeth Urbauer, Ranjith Kumar Ravi Kumar, Doriane Aguanno, Tharan Srikumar, Qixin Liu, Allison M. Barry, Bin Ma, Jonathan Krieger, Dirk Haller, Manuela Schmidt and David Gómez-Varela ()
Additional contact information
Feng Xian: University of Vienna
Malena Brenek: University of Vienna
Christoph Krisp: Bruker Daltonics GmbH & Co. KG
Elisabeth Urbauer: Technical University of Munich
Ranjith Kumar Ravi Kumar: University of Vienna
Doriane Aguanno: Technical University of Munich
Tharan Srikumar: Bruker Daltonics GmbH & Co. KG
Qixin Liu: Rapid Novor
Allison M. Barry: University of Vienna
Bin Ma: Rapid Novor
Jonathan Krieger: Bruker Daltonics GmbH & Co. KG
Dirk Haller: Technical University of Munich
Manuela Schmidt: University of Vienna
David Gómez-Varela: University of Vienna

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract The functional characterization of host-gut microbiome interactions remains limited by the sensitivity of current metaproteomic approaches. Here, we present uMetaP, an ultra-sensitive workflow combining advanced LC-MS technologies with an FDR-validated de novo sequencing strategy, novoMP. uMetaP markedly expands functional coverage and improves the taxonomic detection limit of the gut dark metaproteome by 5000-fold, enabling precise detection and quantification of low-abundance microbial and host proteins. Applied to a mouse model of intestinal injury, uMetaP revealed host-microbiome functional networks underlying tissue damage, beyond genomic findings. Orthogonal validation using transcriptomic data from Crohn’s disease patients confirmed key host protein alterations. Furthermore, we introduce the concept of a druggable metaproteome, mapping functional targets within the host and microbiota. By redefining the sensitivity limits of metaproteomics, uMetaP provides a highly valuable framework for advancing microbiome research and developing therapeutic strategies for microbiome-related diseases.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-61977-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61977-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-61977-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().