%0 Journal Article
%A Valdés-Mas, Rafael
%A Leshem, Avner
%A Zheng, Danping
%A Cohen, Yotam
%A Kern, Lara
%A Zmora, Niv
%A He, Yiming
%A Katina, Corine
%A Eliyahu-Miller, Shimrit
%A Yosef-Hevroni, Tal
%A Richman, Liron
%A Raykhel, Barbara
%A Allswang, Shira
%A Better, Reut
%A Shmueli, Merav
%A Saftien, Aurelia
%A Cullin, Nyssa
%A Slamovitz, Fernando
%A Ciocan, Dragos
%A Ouyang, Kyanna S
%A Mor, Uria
%A Dori-Bachash, Mally
%A Molina, Shahar
%A Levin, Yishai
%A Atarashi, Koji
%A Jona, Ghil
%A Puschhof, Jens
%A Harmelin, Alon
%A Stettner, Noa
%A Chen, Minhu
%A Suez, Jotham
%A Honda, Kenya
%A Lieb, Wolfgang
%A Bang, Corinna
%A Kori, Michal
%A Maharshak, Nitsan
%A Merbl, Yifat
%A Shibolet, Oren
%A Halpern, Zamir
%A Shouval, Dror S
%A Shamir, Raanan
%A Franke, Andre
%A Abdeen, Suhaib K
%A Shapiro, Hagit
%A Savidor, Alon
%A Elinav, Eran
%T Metagenome-informed metaproteomics of the human gut microbiome, host, and dietary exposome uncovers signatures of health and inflammatory bowel disease.
%J Cell
%V 188
%N 4
%@ 0092-8674
%C [Cambridge, Mass.]
%I Cell Press
%M DKFZ-2025-00187
%P 1062-1083.e36
%D 2025
%Z #LA:D480# / 2025 Feb 20;188(4):1062-1083.e36
%X 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.
%K biomarker (Other)
%K diet (Other)
%K inflammatory bowel disease (Other)
%K metagenome-informed metaproteomics (Other)
%K microbiome (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:39837331
%R 10.1016/j.cell.2024.12.016
%U https://inrepo02.dkfz.de/record/298168