Journal Article

DKFZ-2025-00187

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Metagenome-informed metaproteomics of the human gut microbiome, host, and dietary exposome uncovers signatures of health and inflammatory bowel disease.

Valdés-Mas, R. ; Leshem, A. ; Zheng, D. ; Cohen, Y. ; Kern, L. ; Zmora, N. ; He, Y. ; Katina, C. ; Eliyahu-Miller, S. ; Yosef-Hevroni, T. ; Richman, L. ; Raykhel, B. ; Allswang, S. ; Better, R. ; Shmueli, M. ; Saftien, A.DKFZ* ; Cullin, N.DKFZ* ; Slamovitz, F. ; Ciocan, D. ; Ouyang, K. S.DKFZ* ; Mor, U. ; Dori-Bachash, M. ; Molina, S. ; Levin, Y. ; Atarashi, K. ; Jona, G. ; Puschhof, J.DKFZ* ; Harmelin, A. ; Stettner, N. ; Chen, M. ; Suez, J. ; Honda, K. ; Lieb, W. ; Bang, C. ; Kori, M. ; Maharshak, N. ; Merbl, Y. ; Shibolet, O. ; Halpern, Z. ; Shouval, D. S. ; Shamir, R. ; Franke, A. ; Abdeen, S. K. ; Shapiro, H. ; Savidor, A. ; Elinav, E. (Last author)DKFZ*

2025
Cell Press [Cambridge, Mass.]

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Please use a persistent id in citations: doi:10.1016/j.cell.2024.12.016

Abstract: Host-microbiome-dietary interactions play crucial roles in regulating human health, yet their direct functional assessment remains challenging. We adopted metagenome-informed metaproteomics (MIM), in mice and humans, to non-invasively explore species-level microbiome-host interactions during commensal and pathogen colonization, nutritional modification, and antibiotic-induced perturbation. Simultaneously, fecal MIM accurately characterized the nutritional exposure landscape in multiple clinical and dietary contexts. Implementation of MIM in murine auto-inflammation and in human inflammatory bowel disease (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 nutritional MIM assessment enabled the 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.

Keyword(s): biomarker ; diet ; inflammatory bowel disease ; metagenome-informed metaproteomics ; microbiome

Note: #LA:D480# / 2025 Feb 20;188(4):1062-1083.e36

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Contributing Institute(s):

1. Mikrobiom und Krebs (D480)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 60 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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