肠道微生物组与人类癌症关系研究进展
Research Progress on the Relationship between Gut Microbiome and Human Cancer
DOI: 10.12677/AMB.2018.71003, PDF,    国家自然科学基金支持
作者: 夏晶晶, 于景丽*, 赵 吉：内蒙古大学生态与环境学院，内蒙古 呼和浩特；希尼尼根：内蒙古农业大学兽医学院，内蒙古 呼和浩特
关键词: 高通量测序技术；人体微生物组；肠道微生物组；癌症；防控；High-Throughput Sequencing Technology； Human Microbiome； Gut Microbiome； Cancer； Prevention and Control
摘要: 随着高通量测序等相关技术的迅猛发展，微生物组对人体健康影响的研究成为多学科领域的研究热点。肠道微生物菌群在调节人类免疫内稳态和新陈代谢方面发挥非常重要的作用，其结构和功能的改变会引起人类肥胖症、糖尿病、抑郁症甚至癌症等各种疾病。本文基于国内外近十年报道的文献资料综述了人体微生物组的涵义及分布、高通量测序技术在人体微生物组研究中的应用以及肠道微生物组在人类癌症研究中的重要性。迄今癌症仍是人类的头号杀手，本文重点阐述了肠道微生物组与癌症的发生和防控的互作机制，总结了人体肠道微生物组在癌症防控方面所取得的研究成果，提出了当前研究肠道微生物组与癌症等慢性病关系方面所面临的瓶颈问题，并对肠道微生物组与癌症防控研究、肠道等多器官微生物组互作关系研究、以高通量测序为依托的多组学技术应用进行了展望。本文为今后深入研究肠道微生物组与癌症的发生与防控机制、实现癌症的靶向治疗和个性化医疗提供新思路，以期更好的预防和控制癌症。
Abstract: With the rapid development of high throughput sequencing (HTS) and related technologies, studying the effects of microbiome on human health has become a hotspot research in multidisciplinary field. Gut microbiome plays an important role in regulating the human homeostasis and metabolism, while the change of microbiome structure and function can cause human obesity, diabetes, depression and even cancer and other diseases. Based on the reported literatures over the last ten years, this paper summarized the meaning and distribution of human microbiome, reviewed the application of HTS technology in human microbiome research and the importance of gut microbiome in human cancer research. To date cancer has been the number one killer of human beings; this paper focused on the interaction mechanism between cancer’s occurrence, prevention, control and the gut microbiome, and summarized main findings about the role of gut microbiome in cancer’s prevention and control. Furthermore, this paper put forward the bottleneck problems in studying the relationship between gut microbiome and the chronic diseases including cancer at present. Finally, the paper prospected future researches, including the study the role of gut microbiome in preventing and controlling cancer, the interaction of gut and other multi-organs microbiome, the application of multi-omics based on HTS. This paper not only provided the new ideas for studying the interaction mechanism between gut microbiota and cancer’s occurrence, prevention and control, but also laid the foundation for achieving targeted therapy and personalized medicine for cancer in future, in order to better prevent and control human cancer.
文章引用：夏晶晶, 于景丽, 希尼尼根, 赵吉. 肠道微生物组与人类癌症关系研究进展[J]. 微生物前沿, 2018, 7(1): 19-25. https://doi.org/10.12677/AMB.2018.71003

参考文献

[1] Lederberg, J. (2000) Infectious History. Science, 288, 287-293. [Google Scholar] [CrossRef] [PubMed]
[2] Marchesi, J.R. and Ravel, J. (2015) The Vocabulary of Microbiome Research: A Proposal. Microbiome, 3, 31. [Google Scholar] [CrossRef] [PubMed]
[3] Zhao, L. and Shen, J. (2010) Whole-Body Systems Approaches for Gut Microbiota-Targeted, Preventive Healthcare. Journal of Biotechnology, 149, 183-190. [Google Scholar] [CrossRef] [PubMed]
[4] Dishaw, L.J., Cannon, J.P., Litman, G.W. and Parker, W. (2014) Im-mune-Directed Support of Rich Microbial Communities in the Gut Has Ancient Roots. Developmental & Comparative Immunology, 47, 36-51. [Google Scholar] [CrossRef] [PubMed]
[5] Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K.S., Manichanh, C., Nielsen, T., Pons, N., Levenez, F., Yamada, T., Mende, D.R., Li, J., Xu, J., Li, S., Li, D., Cao, J., Wang, B., Liang, H., Zheng, H., Xie, Y., Tap, J., Lepage, P., Bertalan, M., Batto, J.M., Hansen, T., Paslier, D.L., Linneberg, A., Nielsen, H.B., Pelletier, E., Renault, P., Sicheritz-Ponten, T., Turner, K., Zhu, H., Yu, C., Li, S., Jian, M., Zhou, Y., Li, Y., Zhang, X., Li, S., Qin, N., Yang, H., Wang, J., Brunak, S., Doré, J., Guarner, F., Kristiansen, K., Pedersen, O., Parkhill, J., Weissenbach, J., Consortium, M., Bork, P., Ehrlich, S.D. and Wang, J. (2010) A Human Gut Microbial Gene Catalogue Established by Metagenomic Sequencing. Nature, 464, 59-65. [Google Scholar] [CrossRef] [PubMed]
[6] Pfeiffer, J.K. and Sonnenburg, J.L. (2011) The Intestinal Microbiota and Viral Susceptibility. Frontiers in Microbiology, 2, 1-6. [Google Scholar] [CrossRef] [PubMed]
[7] Turnbaugh, P.J., Ley, R.E., Hamady, M., Fraser-Liggett, C., Knight, R. and Gordon, J.I. (2007) The Human Microbiome Project: Exploring the Microbial Part of Ourselves in a Changing World. Nature, 449, 804-810. [Google Scholar] [CrossRef] [PubMed]
[8] Zilber-Rosenberg, I. and Rosenberg, E. (2008) Role of Microorganisms in the Evolution of Animals and Plants: The Hologenome Theory of Evolution. FEMS Microbiology Reviews, 32, 723-735. [Google Scholar] [CrossRef] [PubMed]
[9] 王林, 李冰, 朱健. 高通量测序技术在人工湿地微生物多样性研究中的研究进展[J]. 中国农学通报, 2016, 32(5): 10-15.
[10] 盛华芳, 周宏伟. 微生微生物组学大数据分析方法、挑战与机遇[J]. 南方医科大学学报, 2015, 35(7): 931-934.
[11] Zitvogel, L., Ayyoub, M., Routy, B. and Kroemer, G. (2016) Microbiome and Anticancer Immunosurveillance. Cell, 165, 276-287. [Google Scholar] [CrossRef] [PubMed]
[12] Foster, J.A. and Neufeld, K.A.M. (2013) Gut-Brain Axis: How the Microbiome Influences Anxiety and Depression. Trends in Neurosciences, 36, 305-312. [Google Scholar] [CrossRef] [PubMed]
[13] 陈小林, 任宏宇. 肠道微生物群组与肠道免疫的关系[J]. 胃肠病学和肝病学杂志, 2014, 23(11): 1245-1248.
[14] Ohtani, N. (2015) Microbiome and Cancer. Seminars in Immunopathology, 37, 65-72. [Google Scholar] [CrossRef] [PubMed]
[15] Ahn, J., Sinha, R., Pei, Z., Dominianni, C., Wu, J., Shi, J., Goedert, J.J., Hayes, R.B. and Yang, L. (2013) Human Gut Microbiome and Risk for Colorectal Cancer. Journal of the National Cancer Institute, 105, 1907-1911. [Google Scholar] [CrossRef] [PubMed]
[16] Wang, X., Yang, Y. and Huycke, M.M. (2017) Microbiome-Driven Carcinogenesis in Colorectal Cancer: Models and Mechanisms. Free Radical Biology and Medicine, 105, 3-15. [Google Scholar] [CrossRef] [PubMed]
[17] Gholizadeh, P., Eslami, H., Yousefi, M., Asgharzadeh, M., Aghazadeh, M. and Kafil, H.S. (2016) Role of Oral Microbiome on Oral Cancers: A Review. Biomedicine & Pharmacotherapy, 84, 552-558. [Google Scholar] [CrossRef] [PubMed]
[18] Dejea, C.M., Wick, E.C., Hechenbleikner, E.M., White, J.R., Welch, J.L.M., Rossetti, B.J., Peterson, S.N., Snesrud, E.C., Borisy, G.G., Lazarev, M., Stein, E., Vadivelu, J., Roslani, A.C., Malik, A.A., Wanyiri, J.W., Goh, K.L., Thevambiga, L., Fu, K., Wan, F., LIosa, A.C., Malik, A.A., Housseau, F., Romans, K., Wu, X.Q., McAllister, F.M., Wu, S., Vogelstein, B., Kinzler, K.W., Pardoll, D.M. and Sears, C.L. (2014) Microbiota Organization Is a Distinct Feature of Proximal Colorectal Cancers. Proceedings of the National Academy of Sciences, 111, 18321-18326. [Google Scholar] [CrossRef] [PubMed]
[19] Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S. and Medzhitov, R. (2004) Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis. Cell, 118, 229-241. [Google Scholar] [CrossRef] [PubMed]
[20] Upadhyay, V., Poroyko, V., Kim, T.J., Devkota, S., Fu, S., Liu, D., Tumanov, A.V., Koroleva, E.P., Deng, L.F., Nagler, C., Chang, E.B., Tang, H. and Fu, Y.X. (2012) Lymphotoxin Regulates Commensal Responses to Enable Diet-Induced Obesity. Nature Immunology, 13, 947-953. [Google Scholar] [CrossRef] [PubMed]
[21] Russell, S.L., Gold, M.J., Hartmann, M., Willing, B.P., Thorson, L., Wlodarska, M., Gill, N., Blanchet, M.R., Mohn, W.W., McNagny, K.M. and Finlay, B.B. (2012) Early Life Anti-Biotic-Driven Changes in Microbiota Enhance Susceptibility to Allergic Asthma. EMBO Reports, 13, 440-447. [Google Scholar] [CrossRef] [PubMed]
[22] Susan, E. and Erdman, T.P. (2016) Gut Microbiota Modulate Host Immune Cells in Cancer Development and Growth. Free Radical Biology and Medicine, 105, 28-34.
[23] Wu, N., Yang, X., Zhang, R., Li, J., Xiao, X., Hu, Y., Chen, Y., Yang, F., Lu, N., Wang, Z., Luan, C., Liu, Y., Wang, B., Xiang, C., Wang, Y., Zhao, F., Gao, G.F., Wang, S., Li, L., Zhang, H. and Zhu, B. (2013) Dysbiosis Signature of Fecal Microbiota in Colorectal Cancer Patients. Microbial Ecology, 66, 462-470. [Google Scholar] [CrossRef] [PubMed]
[24] Johansson, M.E., Larsson, J.M.H. and Hansson, G.C. (2011) The Two Mucus Layers of Colon Are Organized by the MUC2 Mucin, Whereas the Outer Layer Is a Legislator of Host-Microbial Interactions. Proceedings of the National Academy of Sciences, 108, 4659-4665. [Google Scholar] [CrossRef] [PubMed]
[25] Costerton, J.W., Stewart, P.S. and Greenberg, E.P. (1999) Bacterial Biofilms: A Common Cause of Persistent Infections. Science, 284, 1318-1322. [Google Scholar] [CrossRef] [PubMed]
[26] Mima, K., Sukawa, Y., Nishihara, R., Qian, Z.R., Yamauchi, M., Inamura, K., Kim, S.A., Masuda, A., Nowak, J.A., Nosho, K., Kostic, A.D., Giannakis, M., Watanabe, H., Bullman, S., Milner, D.A., Harris, C.C., Giovannucci, E., Garraway, L.A., Freeman, G.J., Dranoff, G., Chan, A.T., Garrett, W.S., Huttenhower, C., Fuchs, C.S. and Ogino, S. (2015) Fusobacterium nucleatum and T Cells in Colorectal Carcinoma. JAMA Oncology, 1, 653-661.
[27] Yang, Y., Weng, W., Peng, J., Hong, L., Yang, L., Toiyama, Y., Gao, R., Liu, M., Yin, M., Pan, C., Li, H., Guo, B., Zhu, Q., Wei, Q., Moyer, M.P., Wang, P., Cai, S., Goel, A., Qin, H. and Ma, Y. (2017) Fusobacterium nucleatum Increases Proliferation of Colorectal Cancer Cells and Tumor Development in Mice by Activating Toll-Like Receptor 4 Signaling to Nuclear Factor-κb, and Up-Regulating Expression of Microrna-21. Gastroenterology, 152, 851-866. [Google Scholar] [CrossRef] [PubMed]
[28] Viaud, S., Saccheri, F., Mignot, G., Yamazaki, T., Daillère, R., Hannani, D., Enot, D.P., Pfirschke, C., Engblom, C., Pittet, M.J., Schlitzer, A., Ginhoux, F., Apetoh, L., Chachaty, E., Woerther, P.L., Eberl, G., Bérard, M., Ecobichon, C., Clermont, D., Bizet, C., Gaboriau-Routhiau, V., Cerf-Bensussan, N., Opolon, P., Yessaad, N., Vivier, E., Ryffel, B., Elson, C.O., Doré, J., Kroemer, G., Lepage, P., Boneca, I.G., Ghiringhelli, F. and Zitvogel, L. (2013) The Intestinal Microbiota Modulates the Anticancer Immune Effects of Cyclophosphamide. Science, 342, 971-976. [Google Scholar] [CrossRef] [PubMed]
[29] Kiselyov, A., Bunimovich-Mendrazitsky, S. and Startsev, V. (2015) Treatment of Non-Muscle Invasive Bladder Cancer with Bacillus Calmette-Guerin (BCG): Biological Markers and Simulation Studies. BBA Clinical, 4, 27-34. [Google Scholar] [CrossRef] [PubMed]
[30] Gummesson, A.L., Carlsson, L.M., Storlien, L.H., Bäckhed, F., Lundin, P., Löfgren, L., Stenlöf, K., Lam, Y.Y., Fagerberg, B. and Carlsson, B. (2011) Intestinal Permeability Is Associated with Visceral Adiposity in Healthy Women. Obesity, 19, 2280-2282. [Google Scholar] [CrossRef] [PubMed]
[31] Le, D.T., Wang-Gillam, A., Picozzi, V., Greten, T.F., Crocenzi, T., Springett, G., Morse, M., Zeh, H., Cohen, D., Fine, R.L., Onners, B., Uram, J.N., Laheru, D.A., Lutz, E.R., Solt, S., Murphy, A.L., Skoble, J., Lemmens, E., Grous, J., Dubensky, T., Brockstedt, D.G. and Jaffee, E.M. (2015) Safety and Survival with GVAX Pancreas Prime and Listeria Monocytogenes-Expressing Mesothelin (CRS-207) Boost Vaccines for Metastatic Pancreatic Cancer. Journal of Clinical Oncology, 33, 1325-1333. [Google Scholar] [CrossRef] 
[32] Yao, X., Zhang, C., Xing, Y., Xue, G., Zhang, Q., Pan, F., Wu, G., Hu, Y., Guo, Q., Lu, A., Zhang, X., Zhou, R., Tian, T., Strober, W., Zhao, L. and Meng, G. (2017) Remodelling of the Gut Microbiota by Hyperactive nlrp3 Induces Regulatory T Cells to Maintain Homeostasis. Nature Communications, 8, 1-17. [Google Scholar] [CrossRef] [PubMed]
[33] Willett, W.C. (2008) Overview and Perspective in Human Nutrition. Asia Pacific Journal of Clinical Nutrition, 17, 1-4.
[34] Chen, T., Long, W., Zhang, C., Liu, S., Zhao, L. and Hamaker, B.R. (2017) Fiber-Utilizing Capacity Varies in Prevotella versus Bacteroides Dominated Gut Microbiota. Science Reports, 7, 2594-2600. [Google Scholar] [CrossRef] [PubMed]
[35] Singh, R.K., Chang, H.W., Yan, D., Lee, K.M., Ucmak, D., Wong, K., Abrouk, M., Farahnik, B., Nakamura, M., Zhu, T.H., Bhutani, T. and Liao, W. (2017) Influence of Diet on the Gut Microbiome and Implications for Human Health. Journal of Translational Medicine, 15, 73. [Google Scholar] [CrossRef] [PubMed]
[36] Malan-Muller, S., Valles-Colomer, M., Raes, J., Lowry, C.A., Seedat, S. and Hemmings, S.M.J. (2017) The Gut Microbiome and Mental Health: Implications for Anxiety- and Trauma-Related Disorders. Journal of Integrative Biology, 22, 90-107.
[37] Zitvogel, L., Daillãre, R., Roberti, M.P., Routy, B. and Kroemer, G. (2017) Anticancer Effects of the Microbiome and Its Products. Nature Reviews Microbiology, 15, 465-478. [Google Scholar] [CrossRef] [PubMed]
[38] Yamashita, Y. and Takeshita, T. (2017) The Oral Microbiome and Human Health. Journal of Oral Science, 59, 201-206. [Google Scholar] [CrossRef] [PubMed]
[39] Unger, S.A. and Bogaert, D. (2017) The Respiratory Microbiome and Respiratory Infections. Journal of Infection, 74, S84-S88. [Google Scholar] [CrossRef] 

为你推荐