TY  - JOUR
AU  - Valdés-Mas, Rafael
AU  - Leshem, Avner
AU  - Zheng, Danping
AU  - Cohen, Yotam
AU  - Kern, Lara
AU  - Zmora, Niv
AU  - He, Yiming
AU  - Katina, Corine
AU  - Eliyahu-Miller, Shimrit
AU  - Yosef-Hevroni, Tal
AU  - Richman, Liron
AU  - Raykhel, Barbara
AU  - Allswang, Shira
AU  - Better, Reut
AU  - Shmueli, Merav
AU  - Saftien, Aurelia
AU  - Cullin, Nyssa
AU  - Slamovitz, Fernando
AU  - Ciocan, Dragos
AU  - Ouyang, Kyanna S
AU  - Mor, Uria
AU  - Dori-Bachash, Mally
AU  - Molina, Shahar
AU  - Levin, Yishai
AU  - Atarashi, Koji
AU  - Jona, Ghil
AU  - Puschhof, Jens
AU  - Harmelin, Alon
AU  - Stettner, Noa
AU  - Chen, Minhu
AU  - Suez, Jotham
AU  - Honda, Kenya
AU  - Lieb, Wolfgang
AU  - Bang, Corinna
AU  - Kori, Michal
AU  - Maharshak, Nitsan
AU  - Merbl, Yifat
AU  - Shibolet, Oren
AU  - Halpern, Zamir
AU  - Shouval, Dror S
AU  - Shamir, Raanan
AU  - Franke, Andre
AU  - Abdeen, Suhaib K
AU  - Shapiro, Hagit
AU  - Savidor, Alon
AU  - Elinav, Eran
TI  - Metagenome-informed metaproteomics of the human gut microbiome, host, and dietary exposome uncovers signatures of health and inflammatory bowel disease.
JO  - Cell
VL  - 188
IS  - 4
SN  - 0092-8674
CY  - [Cambridge, Mass.]
PB  - Cell Press
M1  - DKFZ-2025-00187
SP  - 1062-1083.e36
PY  - 2025
N1  - #LA:D480# / 2025 Feb 20;188(4):1062-1083.e36
AB  - 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.
KW  - biomarker (Other)
KW  - diet (Other)
KW  - inflammatory bowel disease (Other)
KW  - metagenome-informed metaproteomics (Other)
KW  - microbiome (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39837331
DO  - DOI:10.1016/j.cell.2024.12.016
UR  - https://inrepo02.dkfz.de/record/298168
ER  -