您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报 (医学版) ›› 2026, Vol. 64 ›› Issue (10): 79-87.doi: 10.6040/j.issn.1671-7554.0.2026.1158

• • 上一篇    

膳食、肠道菌群与抗肿瘤免疫

米萍1,梁金媛1,李新颖1,徐博文2,袁得天1   

  1. 1.山东大学基础医学院, 山东 济南 250012;2.山东大学高等医学研究院, 山东 济南 250012
  • 发布日期:2026-10-10
  • 通讯作者: 袁得天. E-mail:yuandt@sdu.edu.cn
  • 基金资助:
    国家自然科学基金(324B2029,3250050382);山东省博士后创新项目(SDCX-ZG-202601004,SDCX-ZG-202602007)

Diet, gut microbiota and antitumor immunity

MI Ping1, LIANG Jinyuan1, LI Xinying1, XU Bowen2, YUAN Detian1   

  1. 1. School of Basic Medical Sciences, Shandong University, Jinan 250012, Shandong, China;
    2. Advanced Medical Research Institute, Shandong University, Jinan 250012, Shandong, China
  • Published:2026-10-10

摘要: 肠道菌群是影响抗肿瘤免疫及免疫检查点抑制剂疗效的重要宿主因素,膳食则可通过改变营养底物和微生物生态位塑造菌群功能。本文重点综述膳食纤维和氨基酸相关的微生物代谢机制,以及短链脂肪酸、肌苷和胆汁酸对树突状细胞、T细胞及自然杀伤细胞/自然杀伤 T细胞的调节作用,并讨论微生物抗原和先天免疫信号这一互补通路。在证据解释上,区分已在动物模型中建立膳食-菌群-免疫因果链的研究、仅支持菌群或代谢物-免疫环节的研究,以及人群观察性关联。高纤维膳食和部分氨基酸干预已有较完整的动物机制证据;肌苷、部分胆汁酸及微生物抗原交叉反应研究则主要提供下游机制依据,尚不能直接归结为特定膳食的抗肿瘤效应。结合高纤维、氨基酸调整及其他代表性膳食模式的研究,本文提出应围绕膳食底物、微生物功能、物质产生或消耗、空间暴露及靶细胞进行整合评价,并通过随机膳食干预试验验证免疫治疗获益。

关键词: 膳食, 肠道菌群, 抗肿瘤免疫, CD8+ T细胞, 树突状细胞, 免疫检查点抑制剂, 微生物代谢

Abstract: The gut microbiota influences antitumor immunity and responses to immune checkpoint inhibitors, while diet shapes microbial functions by altering nutrient availability and ecological niches. This review focused on microbial mechanisms associated with dietary fiber and amino acids, and on the effects of short-chain fatty acids, inosine, and bile acids on dendritic cells, T cells, and natural killer/natural killer T(NK/NKT)cells. Microbial antigens and innate immune signals were discussed as a complementary pathway. We distinguish studies establishing a diet-microbiota-immunity causal chain in animal models from those supporting only the microbiota- or metabolite-immunity link, and from observational associations in humans. High-fiber diets and selected amino acid interventions have relatively complete mechanistic support in animals, whereas studies of inosine, several bile acids, and microbial antigen cross-reactivity mainly establish downstream mechanisms and cannot directly demonstrate the antitumor effects of a specific diet. Across representative dietary interventions, we propose an integrated assessment of dietary substrates, microbial functions, metabolite production or nutrient consumption, spatial exposure, and target cells. Randomized dietary trials are needed to establish benefits during cancer immunotherapy.

Key words: Diet, Gut microbiota, Antitumor immunity, CD8+ T cells, Dendritic cells, Immune checkpoint inhibitors, Microbial metabolism

中图分类号: 

  • R730
[1] Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy[J]. Science, 2015, 350(6264): 1084-1089.
[2] Vétizou M, Pitt J M, Daillère R, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota[J]. Science, 2015, 350(6264): 1079-1084.
[3] Routy B, Le Chatelier E, Derosa L, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors[J]. Science, 2018, 359(6371): 91-97.
[4] Gopalakrishnan V, Spencer C N, Nezi L, et al. Gut micro-biome modulates response to anti-PD-1 immunotherapy in melanoma patients[J]. Science, 2018, 359(6371): 97-103.
[5] Matson V, Fessler J, Bao R, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metasta-tic melanoma patients[J]. Science, 2018, 359(6371): 104-108.
[6] Wastyk H C, Fragiadakis G K, Perelman D, et al. Gut-microbiota-targeted diets modulate human immune status[J]. Cell, 2021, 184(16): 4137-4153.
[7] Furusawa Y, Obata Y, Fukuda S, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells[J]. Nature, 2013, 504(7480): 446-450.
[8] Luu M, Riester Z, Baldrich A, et al. Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer[J]. Nat Commun, 2021, 12(1): 4077. DOI:10.1038/s41467-021-24331-1
[9] Bachem A, Clarke M, Kong G, et al. Microbiota-derived butyrate promotes a FOXO1-induced stemness program and preserves CD8+ T cell immunity against melanoma[J]. Immunity, 2025, 58(11): 2799-2813.
[10] Mager L F, Burkhard R, Pett N, et al. Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy[J]. Science, 2020, 369(6510): 1481-1489.
[11] Cong J, Liu P, Han Z, et al. Bile acids modified by the intestinal microbiota promote colorectal cancer growth by suppressing CD8+ T cell effector functions[J]. Immunity, 2024, 57(4): 876-889.
[12] Ma C, Han M, Heinrich B, et al. Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells[J]. Science, 2018, 360(6391): eaan5931. DOI:10.1126/science.aan5931
[13] Varanasi S K, Chen D, Liu Y, et al. Bile acid synthesis impedes tumor-specific T cell responses during liver cancer[J]. Science, 2025, 387(6730): 192-201.
[14] Jin W B, Xiao L, Jeong M, et al. Microbiota-derived bile acids antagonize the host androgen receptor and drive anti-tumor immunity[J]. Cell, 2025, 188(9): 2336-2353.
[15] Hang S, Paik D, Yao L, et al. Bile acid metabolites control Th17 and Treg cell differentiation[J]. Nature, 2019, 576(7785): 143-148.
[16] Qiao S, Li T T, Jeong M, et al. Microbiota utilization of intestinal amino acids modulates cancer progression and anticancer immunity[J]. Cell Host Microbe, 2026, 34(1): 18-34.
[17] Lobel L, Fonseca-Pereira D, Nakatsu G, et al. Dietary sulfur amino acids enhance anti-tumor immunity in colon cancer via an NKT cell-XCL1-cDC1 circuit[J]. Immunity, 2026, 59(6): 1708-1725.
[18] Lin N Y-T, Fukuoka S, Koyama S, et al. Microbiota-driven antitumour immunity mediated by dendritic cell migration[J]. Nature, 2025, 644(8078): 1058-1068.
[19] Fluckiger A, Daillère R, Sassi M, et al. Cross-reactivity between tumor MHC class I-restricted antigens and an enterococcal bacteriophage[J]. Science, 2020, 369(6506): 936-942.
[20] Najar T A, Hao Y, Hao Y, et al. Microbiota-induced T cell plasticity enables immune-mediated tumour control[J]. Nature, 2026, 651(8104): 201-210.
[21] Spencer C N, McQuade J L, Gopalakrishnan V, et al. Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response[J]. Science, 2021, 374(6575): 1632-1640.
[22] Qiu Y F, Dizman N, Jiang Y, et al. Clinical outcomes of the DIET study: a randomized controlled phase 2 trial of a high fiber diet intervention(HFDI)in patients with melanoma receiving immune checkpoint blockade(ICB)[J]. J Clin Oncol, 2025, 43(S16): 9511. DOI: 10.1200/JCO.2025.43.16_suppl.9511
[23] Chen Y, Nian F, Wu S, et al. Low-protein diet enhances antitumor immunity in pancreatic cancer through microbiota-derived UDP-galactose[J]. Nature Cancer, 2026. DOI: 10.1038/s43018-026-01222-2
[24] Luo M, Wang Q, Sun Y, et al. Fasting-mimicking diet remodels gut microbiota and suppresses colorectal cancer progression[J]. NPJ Biofilms Microbiomes, 2024, 10(1): 53. DOI: 10.1038/s41522-024-00520-w
[25] Ferrere G, Tidjani Alou M, Liu P, et al. Ketogenic diet and ketone bodies enhance the anticancer effects of PD-1 blockade[J]. JCI Insight, 2021, 6(2): e145207. DOI: 10.1172/jci.insight.145207
[26] Rizvi Z A, Dalal R, Sadhu S, et al. High-salt diet mediates interplay between NK cells and gut microbiota to induce potent tumor immunity[J]. Sci Adv, 2021, 7(37): eabg5016. DOI: 10.1126/sciadv.abg5016
[27] Bolte L A, Lee K A, Björk J R, et al. Association of a mediterranean diet with outcomes for patients treated with immune checkpoint blockade for advanced melanoma[J]. JAMA Oncol, 2023, 9(5): 705-709.
[28] Davar D, Dzutsev A K, McCulloch J A, et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients[J]. Science, 2021, 371(6529): 595-602.
[29] Routy B, Lenehan J G, Miller W H, et al. Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial[J]. Nat Med, 2023, 29(8): 2121-2132.
[30] Duttagupta S, Messaoudene M, Hunter S, et al. Fecal microbiota transplantation plus immunotherapy in non-small cell lung cancer and melanoma: the phase 2 FMT-LUMINate trial[J]. Nat Med, 2026, 32(4): 1337-1350.
[31] Porcari S, Ciccarese C, Heidrich V, et al. Fecal microbiota transplantation plus pembrolizumab and axitinib in metastatic renal cell carcinoma: the randomized phase 2 TACITO trial[J]. Nat Med, 2026, 32(4): 1316-1324.
[1] 李宁 张征 张宏群 高希宝. 济南居民膳食硒摄入量与血清硒参考值调查[J]. 山东大学学报(医学版), 2209, 47(6): 121-122.
[2] 尤欣语, 王文华, 王森, 刘少壮, 黄鑫, 刘腾, 王保珍. 膳食抗氧化能力与代谢相关脂肪性肝病的关联机制及研究进展[J]. 山东大学学报 (医学版), 2026, 64(9): 100-110.
[3] 赵万霞,詹群璋,金婷,刘玉新,曲崇正,吴剑纯. 基于孟德尔随机化分析肠道菌群、血液代谢物和肥胖的因果关系[J]. 山东大学学报 (医学版), 2026, 64(4): 72-82.
[4] 徐晶晶,王新起,张洋,许旺旺,高进. P2X7受体抑制剂对青春期创伤后应激障碍大鼠行为及肠道菌群的影响[J]. 山东大学学报 (医学版), 2025, 63(4): 1-9.
[5] 乔嘉睿,尤欣语,贾雪,王文华,刘少壮,伊向仁,王保珍. 山东省高中生膳食与体质、心理健康的相关性[J]. 山东大学学报 (医学版), 2025, 63(4): 10-18.
[6] 王小磊,方骏,王安,朱武晖,史光军. 两样本孟德尔随机化分析肠道菌群与肝外胆管癌的因果关系[J]. 山东大学学报 (医学版), 2025, 63(4): 44-50.
[7] 徐年兴,魏东,乔俊杰,战炳炎. CD8+、IL-6和PaO2对不可切除ⅢB/C和Ⅳ期非小细胞肺癌免疫治疗触发放射召回性肺炎的预测价值[J]. 山东大学学报 (医学版), 2025, 63(2): 29-35.
[8] 杜凯豪,侯立朝,东小鸽,薛伟伟,何洁洁,罗兰明慧,蒋威,汪占金,王展. 东亚人肠道菌群与胰腺癌关系:基于孟德尔随机化方法的遗传学证据[J]. 山东大学学报 (医学版), 2025, 63(12): 44-52.
[9] 刘绍庭,张薇薇,冉茜,王建. 食品乳化剂与肠道健康[J]. 山东大学学报 (医学版), 2024, 62(8): 18-26.
[10] 田丽君,桑玉洁,孙瑜婧,韩冰,秦成勇,祁建妮. 全身免疫炎症指数对原发性肝癌患者免疫检查点抑制剂治疗相关不良反应的预测价值[J]. 山东大学学报 (医学版), 2024, 62(6): 48-53.
[11] 陈泰宇,唐学贵,唐诗宇,张智彬,陈思敏,李敏,庞峻. 白头翁汤对短肠综合征小鼠肠道功能的影响[J]. 山东大学学报 (医学版), 2023, 61(9): 29-37.
[12] 相宇娇,刘强,刘璐,石艳. 原发免疫性血小板减少症树突状细胞异常免疫反应机制[J]. 山东大学学报 (医学版), 2022, 60(7): 89-97.
[13] 王福立,孙银萍,秦杰,荣建胜. DC-CIK细胞联合EGFR-TKI治疗35例老年晚期EGFR突变肺癌的效果[J]. 山东大学学报 (医学版), 2022, 60(7): 110-117.
[14] 于金明,颜薇薇,陈大卫. 肺癌放射免疫新实践[J]. 山东大学学报 (医学版), 2021, 59(9): 1-8.
[15] 韩晓婷,于霞,董来慧,纳莉,牛艳玲,赵君利. 月见草油对肥胖型不孕女性代谢及肠道菌群的影响[J]. 山东大学学报 (医学版), 2021, 59(2): 48-54.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!