以色列魏茨曼科学研究所Eran Elinav团队发现，基于宏基因组的肠道微生物组、宿主和饮食外显子元蛋白组学揭示健康与炎症性肠病的特征。相关论文于2025年1月20日在线发表在《细胞》杂志上。
研究人员采用基于宏基因组的元蛋白组学（MIM），在小鼠和人类中非侵入性地探索共生菌和致病菌定殖、营养改变以及抗生素引起的干扰过程中物种级别的微生物-宿主相互作用。同时，粪便MIM准确地描述了多种临床和饮食背景下的营养暴露景观。在小鼠自体炎症和人类炎症性肠病（IBD）模型中，MIM揭示了由共生微生物对炎症性宿主信号的抑制反应所驱动的“组成性失调”和伴随的物种特异性“功能性失调”。
微生物转移揭示了这些宿主-共生菌跨响应模式的早期发病动力学，同时预测分析确定了候选粪便宿主-微生物IBD生物标志物蛋白对，表现优于S100A8/S100A9（钙防卫蛋白）。值得注意的是，粪便营养MIM评估使我们能够确定与IBD相关的消费模式、饮食治疗依从性以及小肠消化异常。
总体而言，平行化的饮食-细菌-宿主MIM评估从功能上揭示了塑造胃肠生态的跨域互作网络，同时为微生物组相关疾病提供了个性化的诊断和治疗见解。
据介绍，宿主-微生物-饮食相互作用在调节人体健康中发挥着至关重要的作用，但其直接功能评估仍然具有挑战性。
附：英文原文
Title: Metagenome-informed metaproteomics of the human gut microbiome, host, and dietary exposome uncovers signatures of health and inflammatory bowel disease
Author: Rafael Valdés-Mas, Avner Leshem, Danping Zheng, Yotam Cohen, Lara Kern, Niv Zmora, Yiming He, Corine Katina, Shimrit Eliyahu-Miller, Tal Yosef-Hevroni, Liron Richman, Barbara Raykhel, Shira Allswang, Reut Better, Merav Shmueli, Aurelia Saftien, Nyssa Cullin, Fernando Slamovitz, Dragos Ciocan, Kyanna S. Ouyang, Uria Mor, Mally Dori-Bachash, Shahar Molina, Yishai Levin, Koji Atarashi, Ghil Jona, Jens Puschhof, Alon Harmelin, Noa Stettner, Minhu Chen, Jotham Suez, Kenya Honda, Wolfgang Lieb, Corinna Bang, Michal Kori, Nitsan Maharshak, Yifat Merbl, Oren Shibolet, Zamir Halpern, Dror S. Shouval, Raanan Shamir, Andre Franke, Suhaib K. Abdeen, Hagit Shapiro, Alon Savidor, Eran Elinav
Issue&Volume: 2025-01-20
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.
DOI: 10.1016/j.cell.2024.12.016
Source: https://www.cell.com/cell/abstract/S0092-8674(24)01429-6