肠道微生物群在免疫及乳腺癌中的研究进展
Research Progress of Gut Microbiota in Immunity and Breast Cancer
DOI: 10.12677/acm.2025.153603, PDF,   
作者: 任俊丽, 刘晶怡, 侯 俊：甘肃中医药大学第一临床医学院，甘肃 兰州；马秀芬*：甘肃省妇幼保健院乳腺一科，甘肃 兰州
关键词: 肠道微生物；乳腺癌；免疫功能；新辅助化疗；生物标志物；Gut Microbiota； Breast Cancer； Immune System； Neoadjuvant Therapy； Biomarkers
摘要: 乳腺癌的发病率逐年上升，其发病机制复杂。研究表明，肠道微生物紊乱与乳腺癌的发生发展相关，主要体现在代谢物的产生、激素代谢、免疫失调、DNA损伤以及改变药物作用等机制上，这些共同促进致癌过程。在进化过程中，肠道微生物与宿主形成和谐的共生关系，对塑造免疫系统和诱导保护性免疫发挥了重要的作用。肠道中的微生物可以提高肿瘤的化疗，同时可预测新辅助化疗的疗效，使之有望成为乳腺癌的无创性生物标志物，用于预测和个体化治疗的工具。
Abstract: The incidence of breast cancer is increasing year by year and its pathogenesis is complex. Studies have shown that gut microbial disorders are associated with the development of breast cancer, mainly in the mechanisms of metabolite production, hormone metabolism, immune dysregulation, DNA damage, and altered drug action, which together promote the carcinogenic process. During evolution, gut microbes have formed a harmonious symbiotic relationship with their hosts, playing an important role in shaping the immune system and inducing protective immunity. Microbes in the gut can enhance chemotherapy for tumors, as well as predict neoadjuvant chemotherapy efficacy, giving it promise as a non-invasive biomarker for breast cancer, for prediction and as a tool for individualized treatment.
文章引用：任俊丽, 刘晶怡, 侯俊, 马秀芬. 肠道微生物群在免疫及乳腺癌中的研究进展[J]. 临床医学进展, 2025, 15(3): 184-191. https://doi.org/10.12677/acm.2025.153603

参考文献

[1] Ferlay, J., Colombet, M., Soerjomataram, I., Parkin, D.M., Piñeros, M., Znaor, A., et al. (2021) Cancer Statistics for the Year 2020: An Overview. International Journal of Cancer, 149, 778-789. [Google Scholar] [CrossRef] [PubMed]
[2] Cardoso, F., Kyriakides, S., Ohno, S., Penault-Llorca, F., Poortmans, P., Rubio, I.T., et al. (2019) Early Breast Cancer: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-up. Annals of Oncology, 30, 1194-1220. [Google Scholar] [CrossRef] [PubMed]
[3] Sommer, F., Anderson, J.M., Bharti, R., Raes, J. and Rosenstiel, P. (2017) The Resilience of the Intestinal Microbiota Influences Health and Disease. Nature Reviews Microbiology, 15, 630-638. [Google Scholar] [CrossRef] [PubMed]
[4] Nejman, D., Livyatan, I., Fuks, G., Gavert, N., Zwang, Y., Geller, L.T., et al. (2020) The Human Tumor Microbiome Is Composed of Tumor Type-Specific Intracellular Bacteria. Science, 368, 973-980. [Google Scholar] [CrossRef] [PubMed]
[5] Omar Al-Hassi, H., Ng, O. and Brookes, M. (2017) Tumour-Associated and Non-Tumour-Associated Microbiota in Colorectal Cancer. Gut, 67, 395.2-395. [Google Scholar] [CrossRef] [PubMed]
[6] Riquelme, E., Zhang, Y., Zhang, L., Montiel, M., Zoltan, M., Dong, W., et al. (2019) Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes. Cell, 178, 795-806.e12. [Google Scholar] [CrossRef] [PubMed]
[7] Jin, C., Lagoudas, G.K., Zhao, C., Bullman, S., Bhutkar, A., Hu, B., et al. (2019) Commensal Microbiota Promote Lung Cancer Development via γδ T Cells. Cell, 176, 998-1013.e16. [Google Scholar] [CrossRef] [PubMed]
[8] Urbaniak, C., Gloor, G.B., Brackstone, M., Scott, L., Tangney, M. and Reid, G. (2016) The Microbiota of Breast Tissue and Its Association with Breast Cancer. Applied and Environmental Microbiology, 82, 5039-5048. [Google Scholar] [CrossRef] [PubMed]
[9] Ganal-Vonarburg, S.C., Hornef, M.W. and Macpherson, A.J. (2020) Microbial-Host Molecular Exchange and Its Functional Consequences in Early Mammalian Life. Science, 368, 604-607. [Google Scholar] [CrossRef] [PubMed]
[10] Ruan, W., Engevik, M.A., Spinler, J.K. and Versalovic, J. (2020) Healthy Human Gastrointestinal Microbiome: Composition and Function after a Decade of Exploration. Digestive Diseases and Sciences, 65, 695-705. [Google Scholar] [CrossRef] [PubMed]
[11] Mazmanian, S.K., Round, J.L. and Kasper, D.L. (2008) A Microbial Symbiosis Factor Prevents Intestinal Inflammatory Disease. Nature, 453, 620-625. [Google Scholar] [CrossRef] [PubMed]
[12] Wang, Y., Yin, Y., Chen, X., Zhao, Y., Wu, Y., Li, Y., et al. (2019) Induction of Intestinal Th17 Cells by Flagellins from Segmented Filamentous Bacteria. Frontiers in Immunology, 10, Article 2750. [Google Scholar] [CrossRef] [PubMed]
[13] Atarashi, K., Tanoue, T., Shima, T., Imaoka, A., Kuwahara, T., Momose, Y., et al. (2011) Induction of Colonic Regulatory T Cells by Indigenous Clostridium Species. Science, 331, 337-341. [Google Scholar] [CrossRef] [PubMed]
[14] Yang, W. and Cong, Y. (2021) Gut Microbiota-Derived Metabolites in the Regulation of Host Immune Responses and Immune-Related Inflammatory Diseases. Cellular & Molecular Immunology, 18, 866-877. [Google Scholar] [CrossRef] [PubMed]
[15] Gu, M., Samuelson, D.R., de la Rua, N.M., Charles, T.P., Taylor, C.M., Luo, M., et al. (2022) Host Innate and Adaptive Immunity Shapes the Gut Microbiota Biogeography. Microbiology and Immunology, 66, 330-341. [Google Scholar] [CrossRef] [PubMed]
[16] Schuhmann, M.K., Langhauser, F., Kraft, P. and Kleinschnitz, C. (2017) B Cells Do Not Have a Major Pathophysiologic Role in Acute Ischemic Stroke in Mice. Journal of Neuroinflammation, 14, Article No. 112. [Google Scholar] [CrossRef] [PubMed]
[17] Zhou, W., Liesz, A., Bauer, H., Sommer, C., Lahrmann, B., Valous, N., et al. (2012) Postischemic Brain Infiltration of Leukocyte Subpopulations Differs among Murine Permanent and Transient Focal Cerebral Ischemia Models. Brain Pathology, 23, 34-44. [Google Scholar] [CrossRef] [PubMed]
[18] Gan, Y., Liu, Q., Wu, W., Yin, J., Bai, X., Shen, R., et al. (2014) Ischemic Neurons Recruit Natural Killer Cells That Accelerate Brain Infarction. Proceedings of the National Academy of Sciences of the United States of America, 111, 2704-2709. [Google Scholar] [CrossRef] [PubMed]
[19] Velicer, C.M. (2004) Antibiotic Use in Relation to the Risk of Breast Cancer. JAMA, 291, 827-835. [Google Scholar] [CrossRef] [PubMed]
[20] Luu, T.H., Michel, C., Bard, J., Dravet, F., Nazih, H. and Bobin-Dubigeon, C. (2017) Intestinal Proportion of Blautia sp. Is Associated with Clinical Stage and Histoprognostic Grade in Patients with Early-Stage Breast Cancer. Nutrition and Cancer, 69, 267-275. [Google Scholar] [CrossRef] [PubMed]
[21] Banerjee, S., Tian, T., Wei, Z., Shih, N., Feldman, M.D., Peck, K.N., et al. (2018) Distinct Microbial Signatures Associated with Different Breast Cancer Types. Frontiers in Microbiology, 9, Article 951. [Google Scholar] [CrossRef] [PubMed]
[22] Zhu, J., Liao, M., Yao, Z., Liang, W., Li, Q., Liu, J., et al. (2018) Breast Cancer in Postmenopausal Women Is Associated with an Altered Gut Metagenome. Microbiome, 6, Article No. 136. [Google Scholar] [CrossRef] [PubMed]
[23] Vivarelli, S., Salemi, R., Candido, S., Falzone, L., Santagati, M., Stefani, S., et al. (2019) Gut Microbiota and Cancer: From Pathogenesis to Therapy. Cancers, 11, Article 38. [Google Scholar] [CrossRef] [PubMed]
[24] Rahman, M.M., Islam, M.R., Shohag, S., Ahasan, M.T., Sarkar, N., Khan, H., et al. (2022) Microbiome in Cancer: Role in Carcinogenesis and Impact in Therapeutic Strategies. Biomedicine & Pharmacotherapy, 149, Article ID: 112898. [Google Scholar] [CrossRef] [PubMed]
[25] Doocey, C.M., Finn, K., Murphy, C. and Guinane, C.M. (2022) The Impact of the Human Microbiome in Tumorigenesis, Cancer Progression, and Biotherapeutic Development. BMC Microbiology, 22, Article No. 53. [Google Scholar] [CrossRef] [PubMed]
[26] Kwa, M., Blaser, M.J. and Adams, S. (2016) The Intestinal Microbiome and Estrogen Receptor-Positive Female Breast Cancer. Journal of the National Cancer Institute, 108, djw029.
[27] Komorowski, A.S. and Pezo, R.C. (2019) Untapped “-Omics”: The Microbial Metagenome, Estrobolome, and Their Influence on the Development of Breast Cancer and Response to Treatment. Breast Cancer Research and Treatment, 179, 287-300. [Google Scholar] [CrossRef] [PubMed]
[28] Plottel, C.S. and Blaser, M.J. (2011) Microbiome and Malignancy. Cell Host & Microbe, 10, 324-335. [Google Scholar] [CrossRef] [PubMed]
[29] Laborda-Illanes, A., Sanchez-Alcoholado, L., Dominguez-Recio, M.E., Jimenez-Rodriguez, B., Lavado, R., Comino-Méndez, I., et al. (2020) Breast and Gut Microbiota Action Mechanisms in Breast Cancer Pathogenesis and Treatment. Cancers, 12, Article 2465. [Google Scholar] [CrossRef] [PubMed]
[30] Hu, S., Ding, Q., Zhang, W., Kang, M., Ma, J. and Zhao, L. (2023) Gut Microbial β-Glucuronidase: A Vital Regulator in Female Estrogen Metabolism. Gut Microbes, 15, Article ID: 2236749. [Google Scholar] [CrossRef] [PubMed]
[31] Rosenberg, L., Bethea, T.N., Viscidi, E., Hong, C., Troester, M.A., Bandera, E.V., et al. (2015) Postmenopausal Female Hormone Use and Estrogen Receptor-Positive and-Negative Breast Cancer in African American Women. Journal of the National Cancer Institute, 108, djv361. [Google Scholar] [CrossRef] [PubMed]
[32] Thompson, K.J., Ingle, J.N., Tang, X., Chia, N., Jeraldo, P.R., Walther-Antonio, M.R., et al. (2017) A Comprehensive Analysis of Breast Cancer Microbiota and Host Gene Expression. PLOS ONE, 12, e0188873. [Google Scholar] [CrossRef] [PubMed]
[33] Chen, K.L.A., Liu, X., Zhao, Y.C., Hieronymi, K., Rossi, G., Auvil, L.S., et al. (2018) Long-Term Administration of Conjugated Estrogen and Bazedoxifene Decreased Murine Fecal β-Glucuronidase Activity without Impacting Overall Microbiome Community. Scientific Reports, 8, Article No. 8166. [Google Scholar] [CrossRef] [PubMed]
[34] Keum, N., Greenwood, D.C., Lee, D.H., Kim, R., Aune, D., Ju, W., et al. (2015) Adult Weight Gain and Adiposity-Related Cancers: A Dose-Response Meta-Analysis of Prospective Observational Studies. JNCI: Journal of the National Cancer Institute, 107, djv088. [Google Scholar] [CrossRef] [PubMed]
[35] Hanahan, D. and Weinberg, R.A. (2011) Hallmarks of Cancer: The Next Generation. Cell, 144, 646-674. [Google Scholar] [CrossRef] [PubMed]
[36] Meng, Z., Ye, Z., Zhu, P., Zhu, J., Fang, S., Qiu, T., et al. (2022) New Developments and Opportunities of Microbiota in Treating Breast Cancers. Frontiers in Microbiology, 13, Article 818793. [Google Scholar] [CrossRef] [PubMed]
[37] Scott, A.J., Alexander, J.L., Merrifield, C.A., Cunningham, D., Jobin, C., Brown, R., et al. (2019) International Cancer Microbiome Consortium Consensus Statement on the Role of the Human Microbiome in Carcinogenesis. Gut, 68, 1624-1632. [Google Scholar] [CrossRef] [PubMed]
[38] Álvarez-Mercado, A.I., del Valle Cano, A., Fernández, M.F. and Fontana, L. (2023) Gut Microbiota and Breast Cancer: The Dual Role of Microbes. Cancers, 15, Article 443. [Google Scholar] [CrossRef] [PubMed]
[39] Lu, R., Wu, S., Zhang, Y., Xia, Y., Liu, X., Zheng, Y., et al. (2014) Enteric Bacterial Protein Avra Promotes Colonic Tumorigenesis and Activates Colonic Beta-Catenin Signaling Pathway. Oncogenesis, 3, e105-e105. [Google Scholar] [CrossRef] [PubMed]
[40] Parida, S., Wu, S., Siddharth, S., Wang, G., Muniraj, N., Nagalingam, A., et al. (2021) A Procarcinogenic Colon Microbe Promotes Breast Tumorigenesis and Metastatic Progression and Concomitantly Activates Notch and β-Catenin Axes. Cancer Discovery, 11, 1138-1157. [Google Scholar] [CrossRef] [PubMed]
[41] Carlos-Reyes, Á., López-González, J.S., Meneses-Flores, M., Gallardo-Rincón, D., Ruíz-García, E., Marchat, L.A., et al. (2019) Dietary Compounds as Epigenetic Modulating Agents in Cancer. Frontiers in Genetics, 10, Article 79. [Google Scholar] [CrossRef] [PubMed]
[42] Shankar, S., Kumar, D. and Srivastava, R.K. (2013) Epigenetic Modifications by Dietary Phytochemicals: Implications for Personalized Nutrition. Pharmacology & Therapeutics, 138, 1-17. [Google Scholar] [CrossRef] [PubMed]
[43] Mirzaei, R., Afaghi, A., Babakhani, S., Sohrabi, M.R., Hosseini-Fard, S.R., Babolhavaeji, K., et al. (2021) Role of Microbiota-Derived Short-Chain Fatty Acids in Cancer Development and Prevention. Biomedicine & Pharmacotherapy, 139, Article ID: 111619. [Google Scholar] [CrossRef] [PubMed]
[44] Park, H., Han, J., Park, J.W., Lee, D., Jang, K., Lee, M., et al. (2020) Sodium Propionate Exerts Anticancer Effect in Mice Bearing Breast Cancer Cell Xenograft by Regulating JAK2/STAT3/ROS/p38 MAPK Signaling. Acta Pharmacologica Sinica, 42, 1311-1323. [Google Scholar] [CrossRef] [PubMed]
[45] Semaan, J., El-Hakim, S., Ibrahim, J., Safi, R., Elnar, A.A. and El Boustany, C. (2020) Comparative Effect of Sodium Butyrate and Sodium Propionate on Proliferation, Cell Cycle and Apoptosis in Human Breast Cancer Cells MCF-7. Breast Cancer, 27, 696-705. [Google Scholar] [CrossRef] [PubMed]
[46] Mikó, E., Vida, A., Kovács, T., Ujlaki, G., Trencsényi, G., Márton, J., et al. (2018) Lithocholic Acid, a Bacterial Metabolite Reduces Breast Cancer Cell Proliferation and Aggressiveness. Biochimica et Biophysica Acta (BBA)—Bioenergetics, 1859, 958-974. [Google Scholar] [CrossRef] [PubMed]
[47] Kovács, P., Csonka, T., Kovács, T., Sári, Z., Ujlaki, G., Sipos, A., et al. (2019) Lithocholic Acid, a Metabolite of the Microbiome, Increases Oxidative Stress in Breast Cancer. Cancers, 11, Article 1255. [Google Scholar] [CrossRef] [PubMed]
[48] Cantorna, M.T., Snyder, L. and Arora, J. (2019) Vitamin a and Vitamin D Regulate the Microbial Complexity, Barrier Function, and the Mucosal Immune Responses to Ensure Intestinal Homeostasis. Critical Reviews in Biochemistry and Molecular Biology, 54, 184-192. [Google Scholar] [CrossRef] [PubMed]
[49] Akimbekov, N.S., Digel, I., Sherelkhan, D.K., Lutfor, A.B. and Razzaque, M.S. (2020) Vitamin D and the Host-Gut Microbiome: A Brief Overview. Acta Histochemica et Cytochemica, 53, 33-42. [Google Scholar] [CrossRef] [PubMed]
[50] Zhang, Y., Xia, Y., Zhang, J., Deb, S., Garrett, S. and Sun, J. (2023) Intestinal Vitamin D Receptor Protects against Extraintestinal Breast Cancer Tumorigenesis. Gut Microbes, 15, Article ID: 2202593. [Google Scholar] [CrossRef] [PubMed]
[51] Xie, S., Tan, M., Li, H., Li, L., Zhang, H., Wang, Q., et al. (2023) Study on the Correlation between B Vitamins and Breast Cancer. Cancer Cell International, 23, Article No. 22. [Google Scholar] [CrossRef] [PubMed]
[52] Montassier, E., Gastinne, T., Vangay, P., Al‐Ghalith, G.A., Bruley des Varannes, S., Massart, S., et al. (2015) Chemotherapy‐Driven Dysbiosis in the Intestinal Microbiome. Alimentary Pharmacology & Therapeutics, 42, 515-528. [Google Scholar] [CrossRef] [PubMed]
[53] Panebianco, C., Andriulli, A. and Pazienza, V. (2018) Pharmacomicrobiomics: Exploiting the Drug-Microbiota Interactions in Anticancer Therapies. Microbiome, 6, Article No. 92. [Google Scholar] [CrossRef] [PubMed]
[54] Aarnoutse, R., Ziemons, J., Hillege, L.E., de Vos-Geelen, J., de Boer, M., Bisschop, S.M.P., et al. (2022) Changes in Intestinal Microbiota in Postmenopausal Oestrogen Receptor-Positive Breast Cancer Patients Treated with (Neo)adjuvant Chemotherapy. NPJ Breast Cancer, 8, Article No. 89. [Google Scholar] [CrossRef] [PubMed]
[55] Li, Y., Dong, B., Wu, W., Wang, J., Jin, H., Chen, K., et al. (2022) Metagenomic Analyses Reveal Distinct Gut Microbiota Signature for Predicting the Neoadjuvant Chemotherapy Responsiveness in Breast Cancer Patients. Frontiers in Oncology, 12, Article 865121. [Google Scholar] [CrossRef] [PubMed]

为你推荐