口腔菌群与消化道肿瘤关系的研究进展
Advances in Research on the Relationship between Oral Flora and Gastrointestinal Tumours
DOI: 10.12677/ACM.2023.1351167, PDF,   
作者: 赵健翔*, 付立群, 张庆龙, 王延淼:山东第一医科大学(山东省医学科学院)研究生部,山东 济南;青岛市市立医院消化内科,山东 青岛;曹龙飞, 许 琳:青岛市市立医院消化内科,山东 青岛
关键词: 口腔菌群消化道肿瘤研究进展Oral Flora Digestive Tract Tumours Research Advances
摘要: 口腔是人体内微生物菌群最丰富、最多样化的部位之一,仅次于胃肠道,由超过770种细菌组成。越来越多的证据表明,口腔内的细菌可以通过血行途径和肠道途径转移到胃肠道。口腔菌群向肠道的传播可能会加剧各种消化道肿瘤的进程。本文就口腔菌群与食管癌、胃癌、结直肠癌、胰腺癌等消化系统肿瘤关系展开综述,为后续的相关研究提供一定的参考。
Abstract: The oral cavity is one of the richest and most diverse parts of the body in terms of microflora, second only to the gastrointestinal tract, and is composed of over 770 species of bacteria. There is growing evidence that bacteria from the oral cavity can be transferred to the gastrointestinal tract via the bloodstream and intestinal routes. The spread of oral flora to the gut may exacerbate the progres-sion of various gastrointestinal tumours. This paper reviews the relationship between oral flora and gastrointestinal tumours such as oesophageal, gastric, colorectal and pancreatic cancers, and pro-vides a reference for subsequent studies.
文章引用:赵健翔, 曹龙飞, 付立群, 张庆龙, 王延淼, 许琳. 口腔菌群与消化道肿瘤关系的研究进展[J]. 临床医学进展, 2023, 13(5): 8347-8354. https://doi.org/10.12677/ACM.2023.1351167

参考文献

[1] Escapa, I.F., Chen, T., Huang, Y., et al. (2018) New Insights into Human Nostril Microbiome from the Expanded Hu-man Oral Microbiome Database (eHOMD): A Resource for the Microbiome of the Human Aerodigestive Tract. Msys-tems, 3, e00187-18. [Google Scholar] [CrossRef
[2] Solbiati, J. and Frias-Lopez, J. (2018) Meta-transcriptome of the Oral Microbiome in Health and Disease. Journal of Dental Research, 97, 492-500. [Google Scholar] [CrossRef] [PubMed]
[3] Graves, D.T., Correa, J.D. and Silva, T.A. (2019) The Oral Mi-crobiota Is Modified by Systemic Diseases. Journal of Dental Research, 98, 148-156. [Google Scholar] [CrossRef] [PubMed]
[4] Hajishengallis, G. (2015) Periodontitis: From Microbial Immune Subversion to Systemic Inflammation. Nature Reviews Immunology, 15, 30-44. [Google Scholar] [CrossRef] [PubMed]
[5] Gevers, D., Kugathasan, S., Denson, L.A., et al. (2014) The Treatment-Naive Microbiome in New-Onset Crohn’s Disease. Cell Host & Microbe, 15, 382-392. [Google Scholar] [CrossRef] [PubMed]
[6] Karpinski, T.M. (2019) Role of Oral Microbiota in Cancer De-velopment. Microorganisms, 7, 20. [Google Scholar] [CrossRef] [PubMed]
[7] Kawasaki, M., Ikeda, Y., Ikeda, E., et al. (2021) Oral Infec-tious Bacteria in Dental Plaque and Saliva as Risk Factors in Patients with Esophageal Cancer. Cancer, 127, 512-519. [Google Scholar] [CrossRef] [PubMed]
[8] Narikiyo, M., Tanabe, C., Yamada, Y., et al. (2004) Frequent and Prefer-ential Infection of Treponema denticola, Streptococcus mitis, and Streptococcus anginosus in Esophageal Cancers. Can-cer Science, 95, 569-574. [Google Scholar] [CrossRef] [PubMed]
[9] Peters, B.A., Wu, J., Pei, Z., et al. (2017) Oral Microbi-ome Composition Reflects Prospective Risk for Esophageal Cancers. Cancer Research, 77, 6777-6787. [Google Scholar] [CrossRef
[10] Chen, M.-F., Lu, M.-S., Hsieh, C.-C., et al. (2021) Por-phyromonas gingivalis Promotes Tumor Progression in Esophageal Squamous Cell Carcinoma. Cellular Oncology, 44, 373-384. [Google Scholar] [CrossRef] [PubMed]
[11] Corning, B., Copland, A.P. and Frye, J.W. (2018) The Esophageal Microbiome in Health and Disease. Current Gastroenterology Reports, 20, 39-39. [Google Scholar] [CrossRef] [PubMed]
[12] Libby, P. (2017) Interleukin-1 Beta as a Target for Atherosclerosis Therapy Biological Basis of CANTOS and Beyond. Journal of the American College of Cardiology, 70, 2278-2289. [Google Scholar] [CrossRef] [PubMed]
[13] Carmi, Y., Dotan, S., Rider, P., et al. (2013) The Role of IL-1 Beta in the Early Tumor Cell-Induced Angiogenic Response. Journal of Immunology, 190, 3500-3509. [Google Scholar] [CrossRef] [PubMed]
[14] Jin, L., Yuan, R.Q., Fuchs, A., et al. (1997) Expression of Inter-leukin-1beta in Human Breast Carcinoma. Cancer, 80, 421-434. [Google Scholar] [CrossRef
[15] Voronov, E., Shouval, D.S., Krelin, Y., et al. (2003) IL-1 Is Required for Tumor Invasiveness and Angiogenesis. Proceedings of the National Academy of Sciences of the United States of America, 100, 2645-2650. [Google Scholar] [CrossRef] [PubMed]
[16] Wang, F.M., Liu, H.Q., Liu, S.R., et al. (2005) SHP-2 Promoting Migration and Metastasis of MCF-7 with Loss of E-cadherin, Dephosphorylation of FAK and Secretion of MMP-9 In-duced by IL-1 Beta in Vivo and in Vitro. Breast Cancer Research and Treatment, 89, 5-14. [Google Scholar] [CrossRef] [PubMed]
[17] Li, S.J., Qin, X.B., Chai, S., et al. (2016) Modulation of E-cadherin Expression Promotes Migration Ability of Esophageal Cancer Cells. Scientific Reports, 6, Article No. 21713. [Google Scholar] [CrossRef] [PubMed]
[18] Wong, S.H.M., Fang, C.M., Chuah, L.-H., et al. (2018) E-cadherin: Its Dysregulation in Carcinogenesis and Clinical Implications. Critical Reviews in Oncology Hematology, 121, 11-22. [Google Scholar] [CrossRef] [PubMed]
[19] Gabay, C. (2006) Interleukin-6 and Chronic Inflammation. Arthritis Research & Therapy, 8, S3. [Google Scholar] [CrossRef] [PubMed]
[20] Ishimi, Y., Miyaura, C., Jin, C.H., et al. (1990) IL-6 Is Produced by Osteo-blasts and Induces Bone Resorption. Journal of Immunology (Baltimore, Md.: 1950), 145, 3297-3303. [Google Scholar] [CrossRef
[21] Mathy-Hartert, M., Hogge, L., Sanchez, C., et al. (2008) Inter-leukin-1 beta and Interleukin-6 Disturb the Antioxidant Enzyme System in Bovine Chondrocytes: A Possible Explanation for Oxidative Stress Generation. Osteoarthritis and Cartilage, 16, 756-763. [Google Scholar] [CrossRef] [PubMed]
[22] Murata, M., Thanan, R., Ma, N., et al. (2012) Role of Nitrative and Oxidative DNA Damage in Inflammation-Related Carcinogenesis. Journal of Biomedicine and Biotechnology, 2012, Ar-ticle ID: 623019. [Google Scholar] [CrossRef] [PubMed]
[23] Kossakowska, A.E., Edwards, D.R., Prusinkiewicz, C., Zhang, M.C., et al. (1999) Interleukin-6 Regulation of Matrix Metalloproteinase (MMP-2 and MMP-9) and Tissue Inhibitor of Metallo-proteinase (TIMP-1) Expression in Malignant Non-Hodgkin’s Lymphomas. Blood, 94, 2080-2089. [Google Scholar] [CrossRef
[24] Natali, P., Nicotra, M.R., Cavaliere, R., et al. (1990) Differential Expression of Intercellular Adhesion Molecule 1 in Primary and Metastatic Melanoma Lesions. Cancer Research, 50, 1271-1278.
[25] Janney, A., Powrie, F. and Mann, E.H. (2020) Host-Microbiota Maladaptation in Colorectal Cancer. Nature, 585, 509-517. [Google Scholar] [CrossRef] [PubMed]
[26] Yang, Y., Cai, Q., Shu, X.O., et al. (2017) Abstract 4931: Prospective Study of Oral Microbiome and Colorectal Cancer Risk in Low-Income and African American Populations. Cancer Research, 77, Article No. 4931. [Google Scholar] [CrossRef
[27] Flemer, B., Warren, R.D., Barrett, M.P., et al. (2018) The Oral Microbiota in Colorectal Cancer Is Distinctive and Predictive. Gut, 67, 1454-1463. [Google Scholar] [CrossRef] [PubMed]
[28] Zhang, S., Kong, C., Yang, Y., et al. (2020) Human Oral Micro-biome Dysbiosis as a Novel Non-Invasive Biomarker in Detection of Colorectal Cancer. Theranostics, 10, 11595-11606. [Google Scholar] [CrossRef] [PubMed]
[29] Kostic, A.D., Gevers, D., Pedamallu, C.S., et al. (2012) Genomic Analysis Identifies Association of Fusobacterium with Colorectal Carcinoma. Genome Research, 22, 292-298. [Google Scholar] [CrossRef] [PubMed]
[30] Komiya, Y., Shimomura, Y., Higurashi, T., et al. (2019) Patients with Colorectal Cancer Have Identical Strains of Fusobacterium nucleatum in Their Colorectal Cancer and Oral Cavity. Gut, 68, 1335-1337. [Google Scholar] [CrossRef] [PubMed]
[31] Coppenhagen-Glazer, S., Sol, A., Abed, J., et al. (2015) Fap2 of Fusobacterium nucleatum Is a Galactose-Inhibitable Adhesin Involved in Coaggregation, Cell Adhesion, and Preterm Birth. Infection and Immunity, 83, 1104-1113. [Google Scholar] [CrossRef
[32] Gur, C., Ibrahim, Y., Isaacson, B., et al. (2015) Binding of the Fap2 Protein of Fusobacterium nucleatum to Human Inhibitory Receptor TIGIT Protects Tumors from Immune Cell Attack. Immunity, 42, 344-355. [Google Scholar] [CrossRef] [PubMed]
[33] Kostic, A.D., Chun, E.Y., Robertson, L., et al. (2013) Fuso-bacterium nucleatum Potentiates Intestinal Tumorigenesis and Modulates the Tumor-Immune Microenvironment. Cell Host & Microbe, 14, 207-215. [Google Scholar] [CrossRef] [PubMed]
[34] Abed, J., Emgard, J.E.M., Zamir, G., et al. (2016) Fap2 Mediates Fusobacterium nucleatum Colorectal Adenocarcinoma Enrichment by Binding to Tumor-Expressed Gal-GalNAc. Cell Host & Microbe, 20, 215-225. [Google Scholar] [CrossRef] [PubMed]
[35] Casasanta, M.A., Yoo, C.C., Udayasuryan, B., et al. (2020) Fusobacterium nucleatum Host-Cell Binding and Invasion Induces IL-8 and CXCL1 Secretion That Drives Colorectal Cancer Cell Migration. Science Signaling, 13, eaba9157. [Google Scholar] [CrossRef] [PubMed]
[36] Rubinstein, M.R., Wang, X.W., Liu, W.D., et al. (2013) Fusobacte-rium nucleatum Promotes Colorectal Carcinogenesis by Modulating E-Cadherin/beta-Catenin Signaling via Its FadA Adhesin. Cell Host & Microbe, 14, 195-206. [Google Scholar] [CrossRef] [PubMed]
[37] Rubinstein, M.R., Baik, J.E., Lagana, S.M., et al. (2019) Fuso-bacterium nucleatum Promotes Colorectal Cancer by Inducing Wnt/beta-Catenin Modulator Annexin A1. EMBO Reports, 20, e47638. [Google Scholar] [CrossRef] [PubMed]
[38] Yang, Y.Z., Weng, W.H., Peng, J.J., et al. (2017) Fusobacterium nucleatum Increases Proliferation of Colorectal Cancer Cells and Tumor Development in Mice by Activating Toll-Like Receptor 4 Signaling to Nuclear Factor-kappaB, and Up-Regulating Expression of MicroRNA-21. Gastroenterology, 152, 851-866. [Google Scholar] [CrossRef] [PubMed]
[39] Fan, X., Alekseyenko, A.V., Wu, J., et al. (2016) Human Oral Microbiome and Prospective Risk for Pancreatic Cancer: A Population Based, Nested Case Control Study. Cancer Re-search, 76, Article No. 4350. [Google Scholar] [CrossRef
[40] Pan, C., Xu, X., Tan, L., et al. (2014) The Effects of Por-phyromonas gingivalis on the Cell Cycle Progression of Human Gingival Epithelial Cells. Oral Diseases, 20, 100-108. [Google Scholar] [CrossRef] [PubMed]
[41] Stasiewicz, M. and Karpinski, T.M. (2022) The Oral Microbiota and Its Role in Carcinogenesis. Seminars in Cancer Biology, 86, 633-642. [Google Scholar] [CrossRef] [PubMed]
[42] Moon, J.H., Lee, J.H. and Lee, J.Y. (2015) Subgingival Mi-crobiome in Smokers and Non-Smokers in Korean Chronic Periodontitis Patients. Molecular Oral Microbiology, 30, 227-241. [Google Scholar] [CrossRef] [PubMed]
[43] Tijeras-Raballand, A., Hilmi, M., Astorgues-Xerri, L., et al. (2021) Microbiome and Pancreatic Ductal Adenocarcinoma. Clinics and Research in Hepatology and Gastroenterology, 45, Article ID: 101589. [Google Scholar] [CrossRef] [PubMed]
[44] Friedlander, S.Y.G., Chu, G.C., Snyder, E.L., et al. (2009) Con-text-Dependent Transformation of Adult Pancreatic Cells by Oncogenic K-Ras. Cancer Cell, 16, 379-389. [Google Scholar] [CrossRef] [PubMed]
[45] Aguirre, A.J., Hruban, R.H., Raphael, B.J., et al. (2017) Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma. Cancer Cell, 32, 185-203.e13. [Google Scholar] [CrossRef] [PubMed]
[46] Ren, Z.G., Jiang, J.W., Xie, H.Y., et al. (2017) Gut Microbial Pro-file Analysis by MiSeq Sequencing of Pancreatic Carcinoma Patients in China. Oncotarget, 8, 95176-95191. [Google Scholar] [CrossRef] [PubMed]
[47] Huang, H., Daniluk, J., Liu, Y., et al. (2014) Oncogenic K-Ras Requires Activation for Enhanced Activity. Oncogene, 33, 532-535. [Google Scholar] [CrossRef] [PubMed]
[48] Mao, S., Park, Y., Hasegawa, Y., et al. (2007) Intrinsic Apoptotic Pathways of Gingival Epithelial Cells Modulated by Porphyromonas gingivalis. Cellular Microbiology, 9, 1997-2007. [Google Scholar] [CrossRef] [PubMed]
[49] Ikezawa, K., Hikita, H., Shigekawa, M., et al. (2017) In-creased Bcl-xL Expression in Pancreatic Neoplasia Promotes Carcinogenesis by Inhibiting Senescence and Apoptosis. Cellular and Molecular Gastroenterology and Hepatology, 4, 185-200.e1. [Google Scholar] [CrossRef] [PubMed]
[50] Lofgren, J.L., Whary, M.T., Ge, Z.M., et al. (2011) Lack of Commensal Flora in Helicobacter pylori-Infected INS-GAS Mice Reduces Gastritis and Delays Intraepithelial Neoplasia. Gastroenterology, 140, 210-220. [Google Scholar] [CrossRef] [PubMed]
[51] Wu, J., Xu, S., Xiang, C.J., et al. (2018) Tongue Coating Micro-biota Community and Risk Effect on Gastric Cancer. Journal of Cancer, 9, 4039-4048. [Google Scholar] [CrossRef] [PubMed]
[52] Zhao, Y.N., Zhang, J.L., Cheng, A.S.L., et al. (2020) Gastric Cancer: Ge-nome Damaged by Bugs. Oncogene, 39, 3427-3442. [Google Scholar] [CrossRef] [PubMed]
[53] Enroth, H., Kraaz, W., Engstrand, L., et al. (2000) Helicobacter pylori Strain Types and Risk of Gastric Cancer: A Case-Control Study. Cancer Epidemiology Biomarkers & Prevention, 9, 981-985.
[54] Higashi, H., Nakaya, A., Tsutsumi, R., et al. (2004) Helicobacter pylori CagA Induces Ras-Independent Morphogenetic Response through SHP-2 Recruitment and Activation. Journal of Biological Chemistry, 279, 17205-17216. [Google Scholar] [CrossRef
[55] Tsutsumi, R., Takahashi, A., Azuma, T., et al. (2006) Focal Adhe-sion Kinase Is a Substrate and Downstream Effector of SHP-2 Complexed with Helicobacter pylori CagA. Molecular and Cellular Biology, 26, 261-276. [Google Scholar] [CrossRef
[56] Suzuki, M., Mimuro, H., Kiga, K., et al. (2009) Helicobacter pylori CagA Phosphorylation-Independent Function in Epithelial Proliferation and Inflammation. Cell Host & Microbe, 5, 23-34. [Google Scholar] [CrossRef] [PubMed]
[57] Fan, Y., Mao, R. and Yang, J. (2013) NF-κB and STAT3 Signaling Pathways Collaboratively Link Inflammation to Cancer. Protein & Cell, 4, 176-185. [Google Scholar] [CrossRef] [PubMed]
[58] Nagy, T.A., Frey, M.R., Yan, F., et al. (2009) Helicobacter pylori Regulates Cellular Migration and Apoptosis by Activation of Phosphatidylinositol 3-Kinase Signaling. Journal of Infec-tious Diseases, 199, 641-651. [Google Scholar] [CrossRef] [PubMed]
[59] Nakayama, M., Hisatsune, J., Yamasaki, E., et al. (2009) Helicobacter pylori VacA-Induced Inhibition of GSK3 through the PI3K/Akt Signaling Pathway. Journal of Biological Chemistry, 284, 1612-1619. [Google Scholar] [CrossRef
[60] Lamb, A. and Chen, L.F. (2013) Role of the Helicobacter pylo-ri-Induced Inflammatory Response in the Development of Gastric Cancer. Journal of Cellular Biochemistry, 114, 491-497. [Google Scholar] [CrossRef] [PubMed]