Publicaciones científicas
Metagenome-informed metaproteomics of the human gut microbiome, host, and dietary exposome uncovers signatures of health and inflammatory bowel disease
Rafael Valdés-Mas 1, Avner Leshem 2, Danping Zheng 3, Yotam Cohen 1, Lara Kern 1, Niv Zmora 4, Yiming He 3, Corine Katina 5, Shimrit Eliyahu-Miller 1, Tal Yosef-Hevroni 1, Liron Richman 1, Barbara Raykhel 1, Shira Allswang 1, Reut Better 1, Merav Shmueli 1, Aurelia Saftien 6, Nyssa Cullin 6, Fernando Slamovitz 1, Dragos Ciocan 1, Kyanna S Ouyang 6, Uria Mor 1, Mally Dori-Bachash 1, Shahar Molina 1, Yishai Levin 5, Koji Atarashi 7, Ghil Jona 8, Jens Puschhof 6, Alon Harmelin 9, Noa Stettner 9, Minhu Chen 10, Jotham Suez 11, Kenya Honda 7, Wolfgang Lieb 12, Corinna Bang 13, Michal Kori 14, Nitsan Maharshak 15, Yifat Merbl 1, Oren Shibolet 15, Zamir Halpern 15, Dror S Shouval 16, Raanan Shamir 16, Andre Franke 13, Suhaib K Abdeen 1, Hagit Shapiro 1, Alon Savidor 5, Eran Elinav 17
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.
CITA DEL ARTÍCULO Cell. 2025 Jan 20:S0092-8674(24)01429-6. doi: 10.1016/j.cell.2024.12.016. Online ahead of print.
Nuestros autores
