Simultaneous metagenome-informed metaproteomics of the human gut microbiome, host and dietary exposome uncover functional interactomes in health & IBD
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ABSTRACT: Host-microbiome-dietary interactions play crucial roles in regulating human health, yet direct functional assessment of their interplays, cross-regulations and downstream disease impacts remains challenging. We adopted metagenome-informed metaproteomics (MIM), in both mice and humans, to simultaneously explore host, dietary, and species-level microbiome interactions across diverse scenarios, including commensal and pathogen colonization, nutritional modifications, and antibiotic-induced perturbations. Implementation of MIM in murine auto-inflammation and in human IBD characterized a ‘compositional dysbiosis’ and a concomitant, species-specific ‘functional dysbiosis’ driven by suppressed commensal responses to inflammatory host signals. Microbiome transfers unraveled early-onset kinetics of these host-commensal cross-responsive patterns, while predictive analyses identified candidate fecal host-microbiome IBD biomarker protein pairs outperforming S100A8/S100A9 (calprotectin). Importantly, a simultaneous fecal nutrient assessment enabled determination of IBD-related consumption patterns, dietary treatment compliance and small-intestinal digestive aberrations. Collectively, a parallelized dietary-bacterial-host MIM assessment functionally uncovers trans-kingdom interactomes shaping gastrointestinal ecology, while offering personalized diagnostic and therapeutic insights into microbiome-associated disease.
INSTRUMENT(S):   
ORGANISM(S):  Homo Sapiens (human)  Gut Metagenome  Mus Musculus (mouse) 
TISSUE(S):  Colon, Feces, Ileum 
DISEASE(S): Crohn's Disease,Ulcerative Colitis,Inflammatory Bowel Disease
SUBMITTER:  Rafael Valdes-Mas
Rafael Valdes-Mas   
LAB HEAD:  Eran Elinav
PROVIDER: PXD058570 | Pride | 2025-06-10 
REPOSITORIES:  Pride
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