近日，加拿大麦吉尔大学教授Daniela F. Quail及其课题组提出了饮食-微生物组协同作用是肥胖相关免疫治疗疗效的基础。相关论文发表在2026年7月8日出版的《自然》杂志上。

以12个主题饮食模型为主题，反映了一系列肥胖生物学，研究组描述了与ICI敏感性相关的饮食驱动的代谢、免疫和肠道微生物群特征。该团队发现肥胖相关的ICI反应与代谢功能障碍相关性较差，而是依赖于饮食-肠道轴。致肥性饮食促进了一个稳定的肠道微生物生态系统，能够在短期饮食转换或从无反应模型中移植粪便微生物群（FMTs）后恢复ICI敏感性。将益生菌（如约氏乳杆菌）单菌落在无菌小鼠身上，再加上致肥性饮食，通过丰富微生物衍生的芳香氨基酸代谢物，协同促进肿瘤的消退。

此外，与BMI正常的供者相比，来自高BMI供者的人-母体FMT增强了ICI的疗效，而来自无反应患者的FMT后，致肥性饮食恢复了敏感性。他们的研究为BMI和ICI疗效之间的流行病学关联提供了见解，并表明饮食和肠道微生物群之间的免疫调节协同作用可以用来改善ICI结果和FMT干预。

据悉，生理宿主因素，如肠道微生物组和肥胖，独立影响抗肿瘤免疫和对免疫检查点抑制剂（ICIs）的反应，高体重指数（BMI）与更大的ICI功效有着意想不到的联系。然而，这些因素如何在不同的饮食环境中相互作用仍不清楚。

附：英文原文

Title: Diet–microbiome synergy underlies obesity-associated immunotherapy efficacy

Author: Desharnais, Lysanne, Swaby, Anikka, Messaoudene, Meriem, Dor, Samuel, Yu, Miranda W., Fiset, Benoit, Breton, Valrie, Ponce, Mayra, Hu, Yongjia, Wilson, Liam, Sorin, Mark, Wang, Ye, Dewar, Ken, Pollak, Michael, Elkrief, Arielle, Routy, Bertrand, Walsh, Logan A., Quail, Daniela F.

Issue&Volume: 2026-07-08

Abstract: Physiological host factors, such as the gut microbiome and obesity, independently influence anti-tumour immunity and responses to immune checkpoint inhibitors (ICIs)1, with high body mass index (BMI) having an unexpected link with greater ICI efficacy2,3,4,5,6. However, how these factors interact across diverse dietary contexts remains unclear. Here, using 12 mouse diet models that reflect a spectrum of obesity biology, we characterize diet-driven metabolic, immune and gut microbiota features associated with ICI sensitivity. We find that obesity-associated ICI responses are poorly correlated with metabolic dysfunction and are instead dependent on the diet–gut axis. Obesogenic diets promote a robust and persistent gut microbial ecosystem that is capable of restoring ICI sensitivity following a short-term diet switch or fecal microbiota transplants (FMTs) from non-responder models. Monocolonization of germ-free mice with favourable bacteria such as Lactobacillus johnsonii, together with an obesogenic diet, synergistically promotes tumour regression through an enrichment of microbiota-derived aromatic amino acid metabolites. Moreover, human-to-mouse FMT from donors with a high BMI enhanced ICI efficacy compared with donors with a normal BMI, and an obesogenic diet restored sensitivity following FMT from a non-responder patient. Our study provides insight on epidemiological associations between BMI and ICI efficacy, and suggests that immunomodulatory synergy between diet and the gut microbiota could be leveraged to improve ICI outcomes and FMT interventions.

DOI: 10.1038/s41586-026-10750-x

Source: https://www.nature.com/articles/s41586-026-10750-x