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

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 intr

SUBMITTER: Xian F 

PROVIDER: S-EPMC12274446 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature