肠道微生物在肿瘤发生和治疗中的作用
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摘要
随着对肠道微生物研究的不断深入,越来越多的证据表明肠道微生物可影响人体各种生理过程,并与肿瘤关系密切。研究发现肠道微生物可以促进肿瘤发生,增强化疗药物抗癌活性,介导化疗耐药,调节免疫治疗效果以及减少放疗中肠道损伤。近年来以上研究中所揭示的现象和机制令人匪夷所思,研究中所发现的特征性的菌属有望成为肿瘤预防和诊治新靶标。虽然目前动物和临床试验所获得的证据,令人耳目一新。但鉴于人体肠道微生态研究的复杂性和对其认识的局限性,其在肿瘤发生和治疗中的潜在作用尚需系统深入的研究,文章就此方面的相关研究展开阐述与讨论。
With the deepening of research on intestinal microbiota,more and more evidence indicates that intestinal microbiota affects various physiological processes of the human body and is closely related to tumors,Researches show that intestinal microbiota can promote tumorigenesis,enhance the antitumor effect of chemotherapeutic drugs,mediate chemoresistance,regulate the effect of immunotherapy,and reduce intestinal damage during radiotherapy. The phenomena and mechanisms revealed in the above studies are incredible. Based on the above correlation,the genus found in the study are expected to become the new target of tumor prevention and treatment. The evidence obtained from current animal and clinical trials is refreshing,however,in view of the complexity of human intestinal microecology and the limitations of human understanding,its potential role in tumorigenesis and treatment still needs systematic and in-depth research.
With the deepening of research on intestinal microbiota,more and more evidence indicates that intestinal microbiota affects various physiological processes of the human body and is closely related to tumors,Researches show that intestinal microbiota can promote tumorigenesis,enhance the antitumor effect of chemotherapeutic drugs,mediate chemoresistance,regulate the effect of immunotherapy,and reduce intestinal damage during radiotherapy. The phenomena and mechanisms revealed in the above studies are incredible. Based on the above correlation,the genus found in the study are expected to become the new target of tumor prevention and treatment. The evidence obtained from current animal and clinical trials is refreshing,however,in view of the complexity of human intestinal microecology and the limitations of human understanding,its potential role in tumorigenesis and treatment still needs systematic and in-depth research.
引文
[1]缪丽燕,丁肖梁.肠道菌群与精准药物治疗[J].医学研究生学报,2019,32(5):474-478.
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[27]Wallace BD,Roberts AB,Pollet RM,et al.Structure and Inhibition of Microbiome beta-Glucuronidases Essential to the Alleviation of Cancer Drug Toxicity[J].Chem Biol,2015,22(9):1238-1249.
[28]Sharma P,Allison JP.The future of immune checkpoint therapy[J].Science,2015,348(6230):56-61.
[29]Vetizou M,Pitt JM,Daillere R,et al.Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota[J].Science,2015,350(6264):1079-1084.
[30]Siva A n,Corrales L,Hubert N,et al.Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy[J].Science,2015,350(6264):1084-1089.
[31]Gopalakrishnan V,Spencer CN,Nezi L,et al.Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients[J].Science,2018,359(6371):97-103.
[32]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.
[2]Laukens D,Brinkman BM,Raes J,et al.Heterogeneity of the gut microbiome in mice:guidelines for optimizing experimental design[J].FEMS Microbiol Rev,2016,40(1):117-132.
[3]Wong SH,Zhao L,Zhang X,et al.Gavage of Fecal Samples From Patients With Colorectal Cancer Promotes Intestinal Carcinogenesis in GermFree and Conventional Mice[J].Gastroenterology,2017,153(6):1621-1633.
[4]Garrett WS.Cancer and the microbiota[J].Science,2015,348(6230):80-86.
[5]Sears CL,Garrett WS.Microbes,microbiota,and colon cancer[J].Cell Host Microbe,2014,15(3):317-328.
[6]Guerra L,Guidi R,Frisan T.Do bacterial genotoxins contribute to chronic inflammation,genomic instability and tumor progression?[J]FEBSJ,2011,278(23):4577-4588.
[7]Goodwin AC,Destefano Shields CE,Wu S,et al.Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis[J].Proc Natl Acad Sci U S A,2011,108(37):15354-15359.
[8]Abreu MT,Peek RM Jr.Gastrointestinal malignancy and the microbiome[J].Gastroenterology,2014,146(6):1534-1546.
[9]Rubinstein MR,Wang X,Liu W,et al.Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/beta-catenin signaling via its FadA adhesin[J].Cell Host Microbe,2013,14(2):195-206.
[10]Sears CL.Enterotoxigenic Bacteroides fragilis:a rogue among symbiotes[J].Clin Microbiol Rev,2009,22(2):349-369.
[11]Dai Z,Zhang J,Wu Q,et al.The role of microbiota in the development of colorectal cancer[J].Int J Cancer,2018.
[12]Louis P,Hold GL,Flint HJ.Nat Rev Microbiol,2014,12(10):661-672.
[13]Singh N,Gurav A,Sivaprakasam S,et al.Activation of Gpr109a,receptor for niacin and the commensal metabolite butyrate,suppresses colonic inflammation and carcinogenesis[J].Immunity,2014,40(1):128-139.
[14]Iida N,Dzutsev A,Stewart CA,et al.Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment[J].Science,2013,342(6161):967-970.
[15]Pabla N,Dong Z.Cisplatin nephrotoxicity:mechanisms and renoprotective strategies[J].Kidney Int,2008,73(9):994-1007.
[16]Viaud S,Saccheri F,Mignot G,et al.The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide[J].Science,2013,342(6161):971-976.
[17]Yu T,Guo F,Yu Y,et al.Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy[J].Cell,2017,170(3):548-563.
[18]Lehouritis P,Cummins J,Stanton M,et al.Local bacteria affect the efficacy of chemotherapeutic drugs[J].Sci Rep,2015,514554.
[19]Barker HE,Paget JT,Khan AA,et al.The tumour microenvironment after radiotherapy:mechanisms of resistance and recurrence[J].Nat Rev Cancer,2015,15(7):409-425.
[20]Delia P,Sansotta G,Donato V,et al.Use of probiotics for prevention of radiation-induced diarrhea[J].Tumori,2007,93(2):1-6.
[21]Cui M,Xiao H,Li Y,et al.Faecal microbiota transplantation protects against radiation-induced toxicity[J].EMBO Mol Med,2017,9(4):448-461.
[22]Ciorba MA,Riehl TE,Rao MS,et al.Lactobacillus probiotic protects intestinal epithelium from radiation injury in a TLR-2/cyclo-oxygenase-2-dependent manner[J].Gut,2012,61(6):829-838.
[23]Crawford PA,Gordon JI.Microbial regulation of intestinal radiosensitivity[J].Proc Natl Acad Sci U S A,2005,102(37):13254-13259.
[24]Santulli G.Angiopoietin-like proteins:a comprehensive look[J].Front Endocrinol(Lausanne),2014,5:4.
[25]Paulos CM,Wrzesinski C,Kaiser A,et al.Microbial translocation augments the function of adoptively transferred self/tumor-specific CD8+Tcells via TLR4 signaling[J].J Clin Invest,2007,117(8):2197-2204.
[26]Iida N,Dzutsev A,Stewart CA,et al.Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment[J].Science,2013,342(6161):967-970.
[27]Wallace BD,Roberts AB,Pollet RM,et al.Structure and Inhibition of Microbiome beta-Glucuronidases Essential to the Alleviation of Cancer Drug Toxicity[J].Chem Biol,2015,22(9):1238-1249.
[28]Sharma P,Allison JP.The future of immune checkpoint therapy[J].Science,2015,348(6230):56-61.
[29]Vetizou M,Pitt JM,Daillere R,et al.Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota[J].Science,2015,350(6264):1079-1084.
[30]Siva A n,Corrales L,Hubert N,et al.Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy[J].Science,2015,350(6264):1084-1089.
[31]Gopalakrishnan V,Spencer CN,Nezi L,et al.Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients[J].Science,2018,359(6371):97-103.
[32]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.