膳食、肠道菌群与抗肿瘤免疫

doi:10.6040/j.issn.1671-7554.0.2026.1158

摘要/Abstract

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

米萍,梁金媛,李新颖,徐博文,袁得天. 膳食、肠道菌群与抗肿瘤免疫[J]. 山东大学学报 (医学版), 2026, 64(10): 79-87.

MI Ping, LIANG Jinyuan, LI Xinying, XU Bowen, YUAN Detian. Diet, gut microbiota and antitumor immunity[J]. Journal of Shandong University (Health Sciences), 2026, 64(10): 79-87.

参考文献

[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.

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