The gut microbiota plays a pivotal role in maintaining and regulating the intestinal microenvironment, characterized by its complexity and diversity. With the advancement of genomics and metabolomics technologies, increasing attention has been directed toward the involvement of gut microbiota in tumor initiation, progression, and therapeutic response. Emerging evidence suggests that the gut microbiota not only contributes to tumor development but also modulates the host immune system, thereby influencing antitumor immune responses and enhancing immunotherapy efficacy. A growing body of studies has demonstrated close associations between the gut microbiota, tumor immunotherapy, and related adverse events. Consequently, the gut microbiota holds great potential as a predictive biomarker for tumor occurrence and as a critical regulatory factor affecting immunotherapy outcomes. This review summarizes recent advances in the field, highlighting the interplay between the gut microbiota and tumor immunity, and provides novel perspectives for leveraging gut microbiota to optimize cancer immunotherapy.
HomeArticlesVol 35,2025 No.9Detail
Progress of gut microbiota in tumor immunotherapy
Published on Sep. 26, 2025Total Views: 27 timesTotal Downloads: 14 timesDownloadMobile
- Abstract
- Full-text
- References
Abstract
Full-text
References
1.Garajová I, Balsano R, Wang H, et al. The role of the microbiome in drug resistance in gastrointestinal cancers[J]. Expert Rev Anticancer Ther, 2020, 21(2): 165-176. DOI: 10.1080/14737140.2021.1844007.
2.Kato K, Satoh T, Muro K, et al. A subanalysis of Japanese patients in a randomized, double-blind, placebo-controlled, phase 3 trial of nivolumab for patients with advanced gastric or gastro-esophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2)[J]. Gastric Cancer, 2019, 22(2): 344-354. DOI: 10.1007/s10120-018-0899-6.
3.Jin X, Liu Z, Yang D, et al. Recent progress and future perspectives of immunotherapy in advanced gastric cancer[J]. Front Immunol, 2022, 13: 948647. DOI: 10.3389/fimmu.2022.948647.
4.Peng Z, Cheng S, Kou Y, et al. The gut microbiome is associated with clinical response to anti–PD-1/PD-L1 immunotherapy in gastrointestinal cancer[J]. Cancer Immunol Res, 2020, 8(10): 1251-1261. DOI: 10.1158/2326-6066.Cir-19-1014.
5.Vétizou M, Pitt JM, Daillère R, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota[J]. Science, 2015, 350(6264): 1079-1084. DOI: 10.1126/science.aad1329.
6.汪洪涛. 肠道微生物与人体健康的关系及其影响因素研究进展[J]. 食品安全质量检测学报, 2022, 13(1): 175-181. [Wang HT. Research progress on the relationship between intestinal microorganisms and human health and its influencing factors[J]. Journal of Food Safety and Quality, 2022, 13(1): 175-181.] DOI: 10.19812/j.cnki.jfsq11-5956/ts.2022.01.016.
7.张文晓, 肖纯凌. 益生菌的生理功能及抑癌和抑菌机制的研究进展[J]. 沈阳医学院学报, 2022, 24(2): 187-190, 221. [Zhang WX, Xiao CL. Research progress of physiological functions and mechanisms of anti-cancer and anti-bacterial of probiotics[J].Journal of Shenyang Medical College, 2022, 24(2): 187-190, 221.] DOI: 10.16753/j.cnki.1008-2344.2022.02.019.
8.Han S, Zhuang J, Wu Y, et al. Progress in research on colorectal cancer-related microorganisms and metabolites[J]. Cancer Manag Res, 2020, 12: 8703-8720. DOI: 10.2147/cmar.S268943.
9.魏金凤, 魏晓涛, 张新丽, 等. 肠道菌群失衡与糖尿病肾病的关系及中药防治研究进展[J]. 数理医药学杂志, 2024, 37(5): 371-377. [Wei JF, Wei XT, Zhang XL, et al. Research progress of the relationship between intestinal flora imbalance and diabetic nephropathy and its prevention and treatment by traditional Chinese medicine[J]. Journal of Mathematical Medicine, 2024, 37(5): 371-377.] DOI: 10.12173/j.issn.1004-4337.202312024.
10.Kaźmierczak-Siedlecka K, Roviello G, Catalano M, et al. Gut microbiota modulation in the context of immune-related aspects of Lactobacillus spp. and Bifidobacterium spp. in gastrointestinal cancers[J]. Nutrients, 2021, 13(8): 2674. DOI: 10.3390/nu13082674.
11.Zhou CB, Zhou YL, Fang JY. Gut microbiota in cancer immune response and immunotherapy[J]. Trends Cancer, 2021, 7(7): 647-660. DOI: 10.1016/j.trecan.2021.01.010.
12.Smet A, Kupcinskas J, Link A, et al. The role of microbiota in gastrointestinal cancer and cancer treatment: chance or curse?[J]. Cell Mol Gastroenterol Hepatol, 2022, 13(3): 857-874. DOI: 10.1016/j.jcmgh.2021.08.013.
13.Milovic V, Turchanowa L. Polyamines and colon cancer[J]. Biochem Soc Trans, 2003, 31(2): 381-383. DOI: 10.1042/bst0310381.
14.Hanus M, Parada-Venegas D, Landskron G, et al. Immune system, microbiota, and microbial metabolites: the unresolved triad in colorectal cancer microenvironment[J]. Front Immunol, 2021, 12: 612826. DOI: 10.3389/fimmu.2021.612826.
15.Gobert AP, Latour YL, Asim M, et al. Protective role of spermidine in colitis and colon carcinogenesis[J]. Gastroenterology, 2022, 162(3): 813-827. e818. DOI: 10.1053/j.gastro.2021.11.005.
16.Qiu Q, Lin Y, Ma Y, et al. Exploring the emerging role of the gut microbiota and tumor microenvironment in cancer immunotherapy[J]. Front Immunol, 2021, 11: 612202. DOI: 10.3389/fimmu.2020.612202.
17.Li N, Bai C, Zhao L, et al. The relationship between gut microbiome features and chemotherapy response in gastrointestinal cancer[J]. Front Oncol, 2021, 11: 781697. DOI: 10.3389/fonc.2021.781697.
18.Schluter J, Peled JU, Taylor BP, et al. The gut microbiota is associated with immune cell dynamics in humans[J]. Nature, 2020, 588(7837): 303-307. DOI: 10.1038/s41586-020-2971-8.
19.Newsome RC, Yang Y, Jobin C. The microbiome, gastrointestinal cancer, and immunotherapy[J]. J Gastroenterol Hepatol, 2021, 37(2): 263-272. DOI: 10.1111/jgh.15742.
20.Mager LF, Burkhard R, Pett N, et al. Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy[J]. Science, 2020, 369(6510): 1481-1489. DOI: 10.1126/science.abc3421.
21.Coutzac C, Jouniaux JM, Paci A, et al. Systemic short chain fatty acids limit antitumor effect of CTLA-4 blockade in hosts with cancer[J]. Nat Commun, 2020, 11(1): 2168. DOI: 10.1038/s41467-020-16079-x.
22.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. DOI: 10.1126/science.aan3706.
23.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. DOI: 10.1126/science.aac4255.
24.Gao Y, Bi D, Xie R, et al. Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer[J]. Signal Transduct Target Ther, 2021, 6(1): 398. DOI: 10.1038/s41392-021-00795-x.
25.Vétizou M, Pitt JM, Daillère R, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota[J]. Science, 2015, 350(6264): 1079-1084. DOI: 10.1126/science.aad1329.
26.Sun S, Luo L, Liang W, et al. Bifidobacterium alters the gut microbiota and modulates the functional metabolism of T regulatory cells in the context of immune checkpoint blockade[J]. Proc Natl Acad Sci U S A, 2020, 117(44): 27509-27515. DOI: 10.1073/pnas.1921223117.
27.Sillo TO, Beggs AD, Middleton G, et al. The gut microbiome, microsatellite status and the response to immunotherapy in colorectal cancer[J]. International Journal of Molecular Sciences, 2023, 24(6): 5767. DOI: 10.3390/ijms24065767.
28.Lam KC, Araya RE, Huang A, et al. Microbiota triggers STING-type I IFN-dependent monocyte reprogramming of the tumor microenvironment[J]. Cell, 2021, 184(21): 5338-5356. e5321. DOI: 10.1016/j.cell.2021.09.019.
29.Griffin ME, Espinosa J, Becker JL, et al. Enterococcus peptidoglycan remodeling promotes checkpoint inhibitor cancer immunotherapy[J]. Science, 2021, 373(6558): 1040-1046. DOI: 10.1126/science.abc9113.
30.Lin Y, Xie M, Lau HC, et al. Effects of gut microbiota on immune checkpoint inhibitors in multi-cancer and as microbial biomarkers for predicting therapeutic response[J]. Med, 2025, 6(3): 100530. DOI: 10.1016/j.medj.2024.10.007.
31.Zhu X, Hu M, Huang X, et al. Interplay between gut microbial communities and metabolites modulates pan-cancer immunotherapy responses[J]. Cell Metab, 2025, 37(4): 806-823. e6. DOI: 10.1016/j.cmet.2024.12.013.
32.Chen W, Zheng R, Zhang S, et al. Cancer incidence and mortality in China, 2013[J]. Cancer Lett, 2017, 401: 63-71. DOI: 10.1016/j.canlet.2017.04.024.
33.Zhang X, Pan Z. Influence of microbiota on immunity and immunotherapy for gastric and esophageal cancers[J]. Gastroenterol Rep (Oxf), 2020, 8(3): 206-214. DOI: 10.1093/gastro/goaa014.
34.Zeng Y, Shi Q, Liu X, et al. Dynamic gut microbiota changes in patients with advanced malignancies experiencing secondary resistance to immune checkpoint inhibitors and immune-related adverse events[J]. Front Oncol, 2023, 13: 1144534. DOI: 10.3389/fonc.2023.1144534.
35.Zhang Y, Cheng S, Zou H, et al. Correlation of the gut microbiome and immune-related adverse events in gastrointestinal cancer patients treated with immune checkpoint inhibitors[J]. Front Cell Infect Microbiol, 2023, 13: 1099063. DOI: 10.3389/fcimb.2023.1099063.
36.Chaput N, Lepage P, Coutzac C, et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab[J]. Ann Oncol, 2017, 28(6): 1368-1379. DOI: 10.1093/annonc/mdx108.
37.Liu W, Ma F, Sun B, et al. Intestinal microbiome associated with immune-related adverse events for patients treated with anti-PD-1 inhibitors, a real-world study[J]. Front Immunol, 2021, 12: 756872. DOI: 10.3389/fimmu.2021.756872.
38.Hwang SW, Kim MK, Kweon MN. Gut microbiome on immune checkpoint inhibitor therapy and consequent immune-related colitis: a review[J]. Intest Res, 2023, 21(4): 433-442. DOI: 10.5217/ir.2023.00019.
39.Liu T, Xiong Q, Li L, et al. Intestinal microbiota predicts lung cancer patients at risk of immune-related diarrhea[J]. Immunotherapy, 2019, 11(5): 385-396. DOI: 10.2217/imt-2018-0144.
40.程思远, 韩子翰, 郭晓欢, 等. 肠道菌群与肿瘤免疫治疗疗效及不良反应关系的研究进展[J]. 实用肿瘤学杂志, 2022, 36(6): 520-525. [Cheng SY, Han ZH, Guo XH, et al. Research progress on the relationship between gut microbiota and therapeutic efficacy, and adverse reactions[J]. Practical Oncology Journal, 2022, 36(6): 520-525.]DOI: 10.11904/j.issn.1002-3070.
41.Qu R, Zhang Y, Ma Y, et al. Role of the gut microbiota and its metabolites in tumorigenesis or development of colorectal cancer[J]. Adv Sci (Weinh), 2023, 10(23): e2205563. DOI: 10.1002/advs.202205563.
42.Yan S, Chang J, Hao X, et al. Berberine regulates short-chain fatty acid metabolism and alleviates the colitis-associated colorectal tumorigenesis through remodeling intestinal flora[J]. Phytomedicine, 2022, 102: 154217. DOI: 10.1016/j.phymed.2022.154217.
43.Chen H, Zhang F, Li R, et al. Berberine regulates fecal metabolites to ameliorate 5-fluorouracil induced intestinal mucositis through modulating gut microbiota[J]. Biomed Pharmacother, 2020, 124: 109829. DOI: 10.1016/j.biopha.2020.109829.
44.Lu Q, Zhang Z, Liu S, et al. Inhibition of stemness and PD-L1 expression by Pien Tze Huang enhances T cell-mediated killing of colorectal cancer[J]. J Ethnopharmacol, 2025, 343: 119447. DOI: 10.1016/j.jep.2025.119447.
45.Ye C, Wu C, Li Y, et al. Traditional medicine Xianglian pill suppresses high-fat diet-related colorectal cancer via inactivating TLR4/MyD88 by remodeling gut microbiota composition and bile acid metabolism[J]. J Ethnopharmacol, 2024, 333: 118411. DOI: 10.1016/j.jep.2024.118411.
46.Marchesi JR, Adams DH, Fava F, et al. The gut microbiota and host health: a new clinical frontier[J]. Gut, 2016, 65(2): 330-339. DOI: 10.1136/gutjnl-2015-309990.
47.Lee AH, Rodriguez Jimenez DM, et al. Limosilactobacillus reuteri-a probiotic gut commensal with contextual impact on immunity[J]. Gut Microbes, 2025, 17(1): 2451088. DOI: 10.1080/19490976.2025.2451088.
48.Shi M, Yue Y, Ma C, et al. Pasteurized akkermansia muciniphila ameliorate the LPS-induced intestinal barrier dysfunction via modulating AMPK and NF-κB through TLR2 in Caco-2 Cells[J]. Nutrients, 2022, 14(4): 764. DOI: 10.3390/nu14040764.
49.Baruch EN, Youngster I, Ben-Betzalel G, et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients[J]. Science, 2021, 371(6529): 602-609. DOI: 10.1126/science.abb5920.
50.Jia D, Wang Q, Qi Y, et al. Microbial metabolite enhances immunotherapy efficacy by modulating T cell stemness in pancancer[J]. Cell, 2024, 187(7): 16511665. e21. DOI: 10.1016/j.cell.2024.02.022.
51.Routy B, Lenehan JG, Miller WH Jr, et al. Fecal microbiota transplantation plus antiPD1 immunotherapy in advanced melanoma: a phase I trial[J]. Nat Med, 2023, 29(8): 2121-2132. DOI: 10.1038/s41591-023-02453-x.
52.Zhao W, Lei J, Ke S, et al. Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an openlabel, singlearm, phase II trial (RENMIN215)[J]. EClinicalMedicine, 2023, 66: 102315. DOI: 10.1016/j.eclinm.2023.102315.
53.Kim Y, Kim G, Kim S, et al. Fecal microbiota transplantation improves antiPD1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to antiPD1 inhibitor[J]. Cell Host Microbe, 2024, 32(8): 1380-1393. e9. DOI: 10.1016/j.chom.2024.06.010.
54.Ianiro G, Rossi E, Thomas AM, et al. Faecal microbiota transplantation for the treatment of diarrhoea induced by tyrosinekinase inhibitors in patients with metastatic renal cell carcinoma[J]. Nat Commun, 2020, 11(1): 4333. DOI: 10.1038/s41467-020-18127-y.
55.Yu J, Zhu P, Shi L, et al. Bifidobacterium longum promotes postoperative liver function recovery in patients with hepatocellular carcinoma[J]. Cell Host Microbe, 2024, 32(1): 131-144. e6. DOI: 10.1016/j.chom.2023.11.011.
56.Ciccarese C, Porcari S, Buti S, et al. LBA77 Fecal microbiota transplantation (FMT) versus placebo in patients receiving pembrolizumab plus axitinib for metastatic renal cell carcinoma: Preliminary results of the randomized phase II TACITO trial[J]. Annals of Oncology, 2024, 35(Supplement 2): S1264-S1264. DOI: 10.1016/j.annonc.2024.08.2320.
57.Wong CC, Yu J. Gut microbiota in colorectal cancer development and therapy[J]. Nat Rev Clin Oncol, 2023, 20(7): 429-452. DOI: 10.1038/s41571-023-00766-x.
Popular Papers
-
Analysis of the effect of dietary factors on irritable bowel syndrome by Mendelian randomized method
Apr. 25, 20255412
-
Constructing a predictive model for mild cognitive impairment in elderly individuals with coexisting multiple diseases based on machine learning algorithms
Apr. 25, 20253564
-
Clinical progress of cadonilimab in the treatment of malignant tumor
Jun. 25, 20253400
-
Development and future prospect of project-based learning in medical education from interdisciplinary perspective: taking the teaching practice of Sichuan University as an example
Apr. 25, 20253194
-
Mediating effects of social support and health literacy on self-efficacy and self-advocacy in patients with postoperative chemotherapy for breast cancer
Aug. 25, 20253053
-
Barriers and facilitators to the implementation of integrated community multimorbidity care model in Shanghai-a qualitative study based on normative process theory
Jun. 25, 20252949
-
Research progress on mechanisms of endocrine therapy resistance in prostate cancer
Apr. 25, 20252919
-
The regulatory mechanism of deferoxamine spray in promoting the healing of chronic wounds in third-degree burns
Apr. 25, 20252857