肠道微生态与肿瘤发生和发展关系的研究进展

陈菲,梁婷婷,吕铮,李薇,崔久嵬

肿瘤代谢与营养电子杂志 ›› 2020, Vol. 7 ›› Issue (1) : 7-12.

PDF(601 KB)
PDF(601 KB)
肿瘤代谢与营养电子杂志 ›› 2020, Vol. 7 ›› Issue (1) : 7-12. DOI: 10.16689/j.cnki.cn11-9349/r.2020.01.002
专家论坛

肠道微生态与肿瘤发生和发展关系的研究进展

  • 陈菲,梁婷婷,吕铮,李薇,崔久嵬
作者信息 +

Research progress on the relationship between intestinal microecology and tumorigenesis and development

  • Chen Fei, Liang Tingting, Lyu Zheng, Li Wei, Cui Jiuwei
Author information +
文章历史 +

摘要

肠道微生物种类繁多,形成功能复杂的肠道微生态系统,与宿主互利共生并影响宿主健康,被称为人类的“第二个基因组”。肠道微生态失衡与恶性肿瘤的发生发展密切相关。目前研究结果表明,肠道微生物包括细菌、真菌和病毒的多样性和丰度改变与肿瘤发生发展相关,这些微生物可通过调节宿主炎症与免疫、参与物质代谢、破坏基因稳定性等而影响肿瘤的进程。但各研究结果存在显著差异,可能与研究方法不一致和肠道微生物的复杂性等多种因素有关。通过饮食疗法、补充益生菌或缺失菌种以及应用抗生素等来调节肠道微生态可能成为肿瘤防治的新方法。本文就目前关于肠道微生态与恶性肿瘤发生发展关系的研究进展做简要综述,并指出肠道微生物研究在肿瘤学领域面临的一些挑战和可能的解决办法,以及未来靶向肠道微生态的肿瘤防治新方向,以期为开展进一步肿瘤-微生物研究理清思路,加速研究成果的临床转化,为肿瘤诊断和治疗提供新的策略。

Abstract

There are many types of intestinal microbes, which form a complex intestinal microecosystem. The intestinal microecosystem co-exists with the host and affects the hosts health, and it is known as the "second genome" of human beings. Intestinal microecological imbalance is closely related to the occurrence and development of malignant tumors. The current research results show that changes in the diversity and abundance of intestinal microorganisms including bacteria, fungi and viruses are related to tumorigenesis and its development. These microorganisms can affect tumors by regulating host inflammation and immunity, participating in material metabolism, and disrupting gene stability process. However, there are significant differences in the results of various studies, which may be related to various factors such as inconsistent research methods and the complexity of intestinal microorganisms. Regulation of intestinal microecology through diet therapy, supplementation of probiotics or missing bacteria, and application of antibiotics may become new methods for tumor prevention and treatment. This article summarizes the current research progress on the relationship between intestinal microecology and the occurrence and development of malignant tumors. Also, it points out some challenges and possible solutions for intestinal microbiological research in the field of oncology, as well as the new direction of tumor prevention and treatment targeting intestinal microecology in the future. The review aims to clarify the ideas for further tumor-microbial research and accelerate the clinical transformation of the research results, and provide new strategies for tumor diagnosis and treatment.

关键词

肠道微生态 / 恶性肿瘤 / 发生 / 发展 / 挑战

Key words

Intestinal microbiome / Malignant tumor / Occurrence / Development / Challenge

引用本文

导出引用
陈菲,梁婷婷,吕铮,李薇,崔久嵬. 肠道微生态与肿瘤发生和发展关系的研究进展[J]. 肿瘤代谢与营养电子杂志. 2020, 7(1): 7-12 https://doi.org/10.16689/j.cnki.cn11-9349/r.2020.01.002
Chen Fei, Liang Tingting, Lyu Zheng, Li Wei, Cui Jiuwei. Research progress on the relationship between intestinal microecology and tumorigenesis and development[J]. Electronic Journal of Metabolism and Nutrition of Cancer. 2020, 7(1): 7-12 https://doi.org/10.16689/j.cnki.cn11-9349/r.2020.01.002

参考文献

1.Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell. 2006;124(4):837-848.
2.Nayfach S, Shi ZJ, Seshadri R, et al. New insights from uncultivated genomes of the global human gut microbiome. Nature. 2019;568(7753):505-510.
3.Marchesi JR, Adams DH, Fava F, et al. The gut microbiota and host health:a new clinical frontier. Gut. 2016;65(2):330-339.
4.Dai Z, Coker OO, Nakatsu G, et al. Multi-cohort analysis of colorectal cancer metagenome identified altered bacteria across populations and universal bacterial markers. Microbiome. 2018;6(1):70.
5.Thomas AM, Manghi P, Asnicar F, et al. Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation. Nat Med. 2019;25(4):667-678.
6.Wirbel J, Pyl PT, Kartal E, et al. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat Med. 2019;25(4):679-689.
7.Geller LT, Barzily-Rokni M, Danino T, et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science. 2017;357(6356):1156-1160.
8.Riquelme E, Zhang Y, Zhang L, et al. Tumor microbiome diversity and composition influence pancreatic cancer outcomes. Cell. 2019;178(4):795-806.e712.
9.Jia X, Lu S, Zeng Z, et al. Characterization of gut microbiota, bile acid metabolism, and cytokines in intrahepatic cholangiocarcinoma. Hepatology. 2019;10.1002/hep.30852.
10.Ren Z, Li A, Jiang J, et al. Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma. Gut. 2019;68(6):1014-1023.
11.Goedert JJ, Jones G, Hua X, et al. Investigation of the association between the fecal microbiota and breast cancer in postmenopausal women:a population-based case-control pilot study. J Natl Cancer Inst. 2015;107(8):djv147.
12.Luu TH, Michel C, Bard JM, et al. Intestinal proportion of blautia sp. is associated with clinical stage and histoprognostic grade in patients with early-stage breast cancer. Nutr Cancer. 2017;69(2):267-275.
13.Nakatsu G, Zhou H, Wu WKK, et al. Alterations in enteric virome are associated with colorectal cancer and survival outcomes. Gastroenterology. 2018;155(2):529-541.e525.
14.Hannigan GD, Duhaime MB, Ruffin MTT, et al. Diagnostic potential and interactive dynamics of the colorectal cancer virome. mBio. 2018;9(6):e02248-18.
15.Luan C, Xie L, Yang X, et al. Dysbiosis of fungal microbiota in the intestinal mucosa of patients with colorectal adenomas. Sci Rep. 2015;5:7980.
16.Gao R, Kong C, Li H, et al. Dysbiosis signature of mycobiota in colon polyp and colorectal cancer. Eur J Clin Microbiol Infect Dis. 2017;36(12):2457-2468.
17.Coker OO, Nakatsu G, Dai RZ, et al. Enteric fungal microbiota dysbiosis and ecological alterations in colorectal cancer. Gut. 2019;68(4):654-662.
18.Banerjee S, Wei Z, Tan F, et al. Distinct microbiological signatures associated with triple negative breast cancer. Sci Rep. 2015;5:15162.
19.Hieken TJ, Chen J, Hoskin TL, et al. The microbiome of aseptically collected human breast tissue in benign and malignant disease. Sci Rep. 2016;6:30751.
20.Wang H, Altemus J, Niazi F, et al. Breast tissue, oral and urinary microbiomes in breast cancer. Oncotarget. 2017;8(50):88122-88138.
21.Couturier-maillard A, Secher T, Rehman A, et al. NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J Clin Invest. 2013;123(2):700-711.
22.Man SM, Zhu Q, Zhu L, et al. Critical role for the DNA sensor AIM2 in stem cell proliferation and cancer. Cell. 2015;162(1):45-58.
23.Kesselring R, Glaesner J, Hiergeist A, et al. Irak-m expression in tumor cells supports colorectal cancer progression through reduction of antimicrobial defense and stabilization of STAT3. Cancer Cell. 2016;29(5):684-696.
24.Yang Y, Weng W, Peng J, et al. 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. 2017;152(4):851-866.e824.
25.Wu Y, Wu J, Chen T, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis in mice via a toll-like receptor 4/p21-activated kinase 1 cascade. Dig Dis Sci. 2018;63(5):1210-1218.
26.Tsoi H, Chu ESH, Zhang X, et al. Peptostreptococcus anaerobius induces intracellular cholesterol biosynthesis in colon cells to induce proliferation and causes dysplasia in mice. Gastroenterology. 2017;152(6):1419-1433.e1415.
27.Zhu H, Xu WY, Hu Z, et al. RNA virus receptor Rig-I monitors gut microbiota and inhibits colitis-associated colorectal cancer. J Exp Clin Cancer Res. 2017;36(1):2.
28.Pushalkar S, Hundeyin M, Daley D, et al. The pancreatic cancer microbiome promotes oncogenesis by induction of innate and adaptive immune suppression. Cancer Discov. 2018;8(4):403-416.
29.Pushalkar S, Hundeyin M, Daley D, et al. The pancreatic cancer microbiome promotes oncogenesis by induction of innate and adaptive immune suppression. Cancer Discov. 2018;8(4):403-416.
30.Cremonesi E, Governa V, Garzon JFG, et al. Gut microbiota modulate T cell trafficking into human colorectal cancer. Gut. 2018;67(11):1984-1994.
31.Castellarin M, Warren RL, Freeman JD, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012;22(2):299-306.
32.Mccoy AN, Araujo-perez F, Azcarate-peril A, et al. Fusobacterium is associated with colorectal adenomas. PLoS One. 2013;8(1):e53653.
33.Kostic AD, Chun E, Robertson L, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe. 2013;14(2):207-215.
34.Aykut B, Pushalkar S, Chen R, et al. The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. Nature. 2019;574(7777):264-267.
35.Buchta Rosean C, Bostic RR, Ferey JCM, et al. Preexisting commensal dysbiosis is a host-intrinsic regulator of tissue inflammation and tumor cell dissemination in hormone receptor-positive breast cancer. Cancer Res. 2019;79(14):3662-3675.
36.Chang PV, Hao L, Offermanns S, et al. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl. Acad. Sci. U.S.A. 2014;111(6):2247-2252.
37.Buda A, Qualtrough D, Jepson MA, et al. Butyrate downregulates alpha2beta1 integrin:a possible role in the induction of apoptosis in colorectal cancer cell lines. Gut. 2003;52(5):729-734.
38.Chen HM, Yu YN, Wang JL, et al. Decreased dietary fiber intake and structural alteration of gut microbiota in patients with advanced colorectal adenoma. Am J Clin Nutr. 2013;97(5):1044-1052.
39.Atarashi K, Tanoue T, Oshima K, et al. Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota. Nature. 2013;500(7461):232-236.
40.Smith PM, Howitt MR, Panikov N, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341(6145):569-573.
41.Arpaia N, Campbell C, Fan X, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504(7480):451-455.
42.Bultman SJ, Jobin C. Microbial-derived butyrate:an oncometabolite or tumor-suppressive metabolite?. Cell Host Microbe. 2014;16(2):143-145.
43.Bernstein H, Bernstein C, Payne CM, et al. Bile acids as endogenous etiologic agents in gastrointestinal cancer. World J Gastroenterol. 2009;15(27):3329-3340.
44.Bernstein C, Holubec H, Bhattacharyya AK, et al. Carcinogenicity of deoxycholate, a secondary bile acid. Arch. Toxicol. 2011;85(8):863-871.
45.Ou J, Delany JP, Zhang M, et al. Association between low colonic short-chain fatty acids and high bile acids in high colon cancer risk populations. Nutr Cancer. 2012;64(1):34-40.
46.Ou J, Carbonero F, Zoetendal EG, et al. Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans. Am J Clin Nutr. 2013;98(1):111-120.
47.Ma C, Han M, Heinrich B, et al. Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells. Science. 2018;360(6391):eaan5931.
48.Singh V, Yeoh BS, Chassaing B, et al. Dysregulated microbial fermentation of soluble fiber induces cholestatic liver cancer. Cell. 2018;175(3):679-694.e622.
49.Plottel CS, Blaser MJ. Microbiome and malignancy. Cell host & microbe. 2011;10(4):324-335.
50.Wang X, Huycke MM. Extracellular superoxide production by Enterococcus faecalis promotes chromosomal instability in mammalian cells. Gastroenterology. 2007;132(2):551-561.
51.Huycke MM, Abrams V, Moore DR. Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis. 2002;23(3):529-536.
52.Cuevas-ramos G, Petit CR, Marcq I, et al. Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. Proc Natl Acad Sci U S A. 2010;107(25):11537-11542.
53.Cougnoux A, Delmas J, Gibold L, et al. Small-molecule inhibitors prevent the genotoxic and protumoural effects induced by colibactin-producing bacteria. Gut. 2016;65(2):278-285.
54.Raskov H, Burcharth J, Pommergaard HC. Linking gut microbiota to colorectal cancer. J Cancer. 2017;8(17):3378-3395.
55.Dejea CM, Fathi P, Craig JM, et al. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science. 2018;359(6375):592-597.
56.Chung L, Orberg ET, Geis AL, et al. Bacteroides fragilis Toxin Coordinates a Pro-carcinogenic Inflammatory Cascade via Targeting of Colonic Epithelial Cells. Cell host & microbe. 2018;23(3):421.
57.Sobhani I, Bergsten E, Couffin S, et al. Colorectal cancer-associated microbiota contributes to oncogenic epigenetic signatures. Proc Natl Acad Sci U S A. 2019;116(48):24285-24295.
58.He Z, Gharaibeh RZ, Newsome RC, et al. Campylobacter jejuni promotes colorectal tumorigenesis through the action of cytolethal distending toxin. Gut. 2019;68(2):289-300.
59.Sontheimer-phelps A, Hassell BA, Ingber DE. Modelling cancer in microfluidic human organs-on-chips. Nat Rev Cancer. 2019;19(2):65-81.
60.Drost J, Clevers H. Organoids in cancer research. Nat Rev Cancer. 2018;18(7):407-418.
61.Johnson AJ, Vangay P, Al-Ghalith GA, et al. Daily sampling reveals personalized diet-microbiome associations in humans. Cell host & microbe. 2019;25(6):789-802.e785.
62.Tsuda A, Suda W, Morita H, et al. Influence of proton-pump inhibitors on the luminal microbiota in the gastrointestinal tract. Clin Transl Gastroenterol. 2015;6:e89.
63.Freedberg DE, Toussaint NC, Chen SP, et al. Proton pump inhibitors alter specific taxa in the human gastrointestinal microbiome:a crossover trial. Gastroenterology. 2015;149(4):883-885.e889.
64.Forslund K, Hildebrand F, Nielsen T, et al. Disentangling type 2 diabetes and metformin treatment signatures in the human gut microbiota. Nature. 2015;528(7581):262-266.
65.Maier L, Pruteanu M, Kuhn M, et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018;555(7698):623-628.
66.Donia MS, Cimermancic P, Schulze CJ, et al. A systematic analysis of biosynthetic gene clusters in the human microbiome reveals a common family of antibiotics. Cell. 2014;158(6):1402-1414.
67.Zipperer A, Konnerth MC, Laux C, et al. Human commensals producing a novel antibiotic impair pathogen colonization. Nature. 2016;535(7613):511-516.
68.Yatsunenko T, Rey FE, Manary MJ, et al. Human gut microbiome viewed across age and geography. Nature. 2012;486(7402):222-227.

基金

吉林省科技厅重点实验室建设项目(20170622011JC)
吉林省科学技术厅科技发展计划项目吉林省重点实验室 专项(20180101009JC)
 吉林省发展和改革委员会省级产业创新专项资金项目 (2017C022)
吉林省科技厅科技发展计划项目(20190303146SF)
吉林省财政厅(2018SCZWSZX-010)

PDF(601 KB)

Accesses

Citation

Detail

段落导航
相关文章

/