肠道微生态与胰腺癌关系的研究进展
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摘要
胰腺癌是消化系统常见的恶性肿瘤之一。目前胰腺癌的病因尚未完全明确,除了与吸烟、饮酒、糖尿病和慢性胰腺炎等因素存在一定的相关性外,近年来研究发现肠道微生态紊乱也是胰腺癌发病的重要危险因素,且肠道微生态可能作为胰腺癌诊断和治疗的新方向。因此,本文就二者的相关性及肠道微生态在胰腺癌发病、诊断及治疗等方面的研究进展进行综述。
Pancreatic cancer is one of the common malignancies in digestive system. The etiology of pancreatic cancer is not clear at present. Besides the correlation with smoking, alcohol, diabetes and chronic pancreatitis, the inordinate gut microbiota is also an importantly risk factor for pancreatic cancer in recent researches. Meanwhile, the gut microbiota is likely a new direction for the diagnosis and treatment of pancreatic cancer. Therefore, this review summarize the correlation between gut microbiota and pancreatic cancer, as well as the research progress of gut microbiota in the incidence, diagnosis and treatment of pancreatic cancer.
Pancreatic cancer is one of the common malignancies in digestive system. The etiology of pancreatic cancer is not clear at present. Besides the correlation with smoking, alcohol, diabetes and chronic pancreatitis, the inordinate gut microbiota is also an importantly risk factor for pancreatic cancer in recent researches. Meanwhile, the gut microbiota is likely a new direction for the diagnosis and treatment of pancreatic cancer. Therefore, this review summarize the correlation between gut microbiota and pancreatic cancer, as well as the research progress of gut microbiota in the incidence, diagnosis and treatment of pancreatic cancer.
引文
[1] LIN QJ, YANG F, JIN C, et al.Current status and progress of pancreatic cancer in China[J].World J Gastroentero, 2015,21(26):7988-8003.
[2]王滨.胰腺癌危险因素的研究进展[J].职业与健康,2017, 33(21):3007-3009.
[3] MEI QX, HUANG CL, LUO SZ, et al.Characterization of the duodenal bacterial microbiota in patients with pancreatic head cancer vs. healthy controls[J]. Pancreatology, 2018,18(4):438-445.
[4] EIBL G,ROZENGURT E. KRAS, YAP,and obesity in pancreatic cancer:a signaling network with multiple loops[J]. Semin Cancer Biol, 2019,54:50-62.
[5] GENTILE CL,WEIR TL. The gut microbiota at the intersection of diet and human health[J]. Science, 2018,362(641 6):776-780.
[6] SEKIROV I,RUSSELL SL,ANTUNES LC,et al. Gut microbiota in health and disease[J]. Physiol Rev, 2010,90(3):859-904.
[7] SONNENBURG JL, BACKHED F. Dietmicrobiota interactions as moderators of human metabolism[J]. Nature,2016, 535(761 0):56-64.
[8] BELKAID Y, HAND TW. Role of the microbiota in immunity and inflammation[J]. Cell, 2014,157(1):121-141.
[9] LOZUPONE CA, STOMBOUGH JI,GORDON JI, et al. Diversity, stability and resilience of the human gut microbiota[J]. Nature, 2012,489(741 5):220-230.
[10] O'HARA AM, SHANAHAN F. The gut flora as a forgotten organ[J].EMBO Rep,2006, 7(7):688-693.
[11] YAMASHITA T, EMOTO T, SASAKI N,et al. gut microbiota and coronary artery disease[J].Int Heart J, 2016,57(6):663-671.
[12] MANGIOLA F, IANIRO G, FRANCESCHI F,et al. Gut microbiota in autism and mood disorders[J]. World J Castroentero, 2016,22(1):361-368.
[13] TANG WH,KITAI T, HAZEN SL. Gut microbiota in cardiovascular health and disease[J]. Circ Res, 201 7,120(7):1183-1196.
[14] PRATAS D, SILVA RM, PINHO AJ, et al.An alignment-free method to find and visualise rearrangements between pairs of DNA sequences[J]. Sci Rep,2015, 5:10203.
[15]杨波,铁宝霞,蔡小玲,等.肠道微生态研究方法及应用研究进展[J].广西医学,2018, 40(10):1219-1221.
[16]梁跃斌,李彬春,李艳琴.基于宏基因组学方法挖掘新型α-L-鼠-李糖苷酶资源[J].中国生物化学与分子生物学报,2017,31(1):66-72.
[17] HOFF KJ, TECH M, LINGNER T, et al.Gene prediction in metagenomic fragments:a large scale machine learning approach[J]. BMC Bioinformatics, 2008, 9:21 7.
[18] GELLER LT, BARZILYROKNI M,DANION T, et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine[J]. Science, 2017,357(6356):1156-1160.
[19] ZITVOGEL L, DAILLERE R, ROBERTI MP, et al.Anticancer effects of the microbiome and its products[J]. Nat Rev Microbiol,2017, 15(8):465-478.
[20] LIU SZ, CHEN WQ, WANG N, et al.Dietary factors and risk of pancreatic cancer:a multi-centre case-control study in ChinaU]. Asian Pac J Cancer Prev, 2014, 1 5(1 8):7947-7950.
[21] WU QJ, WU L, ZHENG LQ, et al.Consumption of fruit and vegetables reduces risk of pancreatic cancer:evidence from epidemiological studies[J]. Eur J Cancer Prev, 2016,25(3):1 96-205.
[22] BAO Y, NG K, WOLPIN BM, et al.Predited vitamin D status and pancreatic cancer risk in two prospective cohort studies[J]. Brit J Cancer, 201 0, 1 02(9):1422-1 427.
[23] CHUANG SC, GALLO V, MICHAUD D,et al. Exposure to environmental tobacco smoke in childhood and incidence of cancer in adulthood in never smokers in the European prospective investigation into cancer and nutrition[J]. Cancer Cause Control,2011,22(3):487-494.
[24]金玲玲,王晓林,曹仕琼.外泌体与胰腺癌化疗耐药的研究进展[J].实用医学杂志,2018, 34(5):860-863.
[25] HUSSAIN SP, HOFSETH LJ, HARRIS CC.Radical causes of cancer[J], Nat Rev Cancer, 2003, 3(4):276-285.
[26] SIVAN A, CORRALES L, HUBERT N,et al. Commensal bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy[J].Science, 2015, 350(6264):1084-1089.
[27] FEI N, ZHAO L. An opportunistic pathogen isolated from the gut of an obese human causes obesityin germfree mice[J]. ISME J, 2013,7(4):880-884.
[28] HAKKAK R, KOROURIAN S, FOLEY SL,et al. Assessment of gut microbiota populations in lean and obese Zucker rats[J]. PLoS One, 201 7, 1 2(7):e0181451.
[29] BEYER G, D'HAESE JG, ORMANNS S, et al.Chronic pancreatitis and pancreatic cancertumor risk and screening[J]. Deut Med Wochenschr,2018, 143(12):895-906.
[30] SONG S, WANG B, ZHANG X, et al.Long-term diabetes mellitus is associated with an increased risk of pancreatic cancer:a meta-analysis[J].PLoS One, 201 5, 1 0(7):e0134321.
[31] LARSEN N, VOGENSEN FK, VAN DEN BERG FW, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults[J].PLoS One, 2010, 5(2):e9085.
[32] CRUZ NG, SOUSA LP, SOUSA MO, et al.The linkage between inflammation and type 2 diabetes mellitus[J]. Diabetes Res Clin Pract, 201 3, 99(2):85-92.
[33] KOMURA T, SAKAI Y, HONDA M, et al.CD14+monocytes are vulnerable and functionally impaired under endoplasmic reticulum stress in patients with type 2diabetes[J]. Diabetes, 2010, 59(3):634-643.
[34] RIDLON J M, KANG DJ, HYLEMON PB,et al. Gut microbiota, cirrhosis, and alcohol regulate bile acid metabolism in the gut[J]. Digest Dis, 201 5,33(3):338-345.
[35] PESIC M, GRETEN FR. Inflammation and cancer:tissue regeneration gone awry[J]. Curr Opin Cell Biol, 2016,43:55-61.
[36] KUNDU JK, SURH YJ. Inflammation:gearing the journey to cancer[J]. Mutat Res, 2008, 659(1):1 5-30.
[37] HUMPHRIS J L, JOHNS AL, SIMPSON SH,et al. Clinical and pathologic features of familial pancreatic cancer[J]. Cancer,2015, 120(23):3669-3675.
[38] ZAMBIRINIS CP, PUSHALKAR S,SAXENA D, et al. Pancreatic cancer,inflammation, and microbiome.[J].CancerJ, 2014, 20(3):195-202.
[39] HOUTEN SM, WATANABE M, AUWERX J.Endocrine functions of bile acids[J].EMBO J, 2014, 25(7):141 9-1425.
[40] TUCKER ON, DAN N EN BERG AJ,YANG EK, et al. Bile acids induce cyclooxyoenase-2 expression inhuman pancreatic cancer cell lines[J].Carcinogenesis, 2004, 25(3):419-423.
[41]刘昌,吕毅,王浩华,等.胆汁酸对人胰腺癌细胞的毒性作用[J].医学争鸣,2003, 24(22):2084-2086.
[42]李淑玲,李闻.胆汁酸与肠道微生态的研究进展[J].胃肠病学和肝病学杂志,2018,27(4):466-470.
[43]王维斌,董良博,赵邦博,等.法尼醇X受体表达与胰腺癌患者预后及病理分期相关[J].基础医学与临床,2018,38(3):394-399.
[44] TORRES PJ, FLETCHER EM, GIBBONS SM,et al. Characterization of the salivary microbiome in patients with pancreatic cancer[J]. PeerJ, 2015, 3(11):e1373.
[45] SHADNOUSH M, HOSSEINI RS,KHALILNEZHAD A, et al. Effects of probiotics on gut microbiota in patients with inflammatory bowel disease:A double-blind, placebocontrolled clinical trial[J]. Korean J Gastroenterol, 201 5, 65(4):21 5-221.
[46] BOLDEN JE, PEART MJ, JOHNSTONE RW.Anticancer activities of histone deacetylase inhibitors[J]. Nat Rev Drug Discov, 2006, 5(9):769-784.
[47] CORRA S, KAZAKOFF K, MOGAKI M, et al.Modification of antigen expression in human and hamster pancreatic cancer cell lines induced by sodium butyrate[J]. Teratog Carcinog Mutagen,1993, 13(5):199-21 5.
[48] FARROW B,RYCHAHOU P,O'CONNOR KL,et al. Butyrate inhibits pancreatic cancer invasion[J].J Gastrointest Surg, 2003,7(7):864-870.
[49]仓晓风,万荣.肠道微生态与胰腺疾病[J].现代消化及介入诊疗,2017,22(1):160-162.
[50]王艺,王理伟.胰腺癌患者免疫状态及免疫治疗进展[J].肿瘤,201 8,38(6):610-616.
[51] HORAI R, ZARATE-BLADES CR,DILLENBURG-PILLA P, et al.Microbiota-dependent activation of an autoreactive T cell receptor provokes autoimmunity in an immunologically privileged site[J]. Immunity, 2015,43(2):343-353.
[52] VETIZOU M, PITT J M, DAILLERE R,et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota[J]. Science, 2015,350(6264):1 079-1084.
[2]王滨.胰腺癌危险因素的研究进展[J].职业与健康,2017, 33(21):3007-3009.
[3] MEI QX, HUANG CL, LUO SZ, et al.Characterization of the duodenal bacterial microbiota in patients with pancreatic head cancer vs. healthy controls[J]. Pancreatology, 2018,18(4):438-445.
[4] EIBL G,ROZENGURT E. KRAS, YAP,and obesity in pancreatic cancer:a signaling network with multiple loops[J]. Semin Cancer Biol, 2019,54:50-62.
[5] GENTILE CL,WEIR TL. The gut microbiota at the intersection of diet and human health[J]. Science, 2018,362(641 6):776-780.
[6] SEKIROV I,RUSSELL SL,ANTUNES LC,et al. Gut microbiota in health and disease[J]. Physiol Rev, 2010,90(3):859-904.
[7] SONNENBURG JL, BACKHED F. Dietmicrobiota interactions as moderators of human metabolism[J]. Nature,2016, 535(761 0):56-64.
[8] BELKAID Y, HAND TW. Role of the microbiota in immunity and inflammation[J]. Cell, 2014,157(1):121-141.
[9] LOZUPONE CA, STOMBOUGH JI,GORDON JI, et al. Diversity, stability and resilience of the human gut microbiota[J]. Nature, 2012,489(741 5):220-230.
[10] O'HARA AM, SHANAHAN F. The gut flora as a forgotten organ[J].EMBO Rep,2006, 7(7):688-693.
[11] YAMASHITA T, EMOTO T, SASAKI N,et al. gut microbiota and coronary artery disease[J].Int Heart J, 2016,57(6):663-671.
[12] MANGIOLA F, IANIRO G, FRANCESCHI F,et al. Gut microbiota in autism and mood disorders[J]. World J Castroentero, 2016,22(1):361-368.
[13] TANG WH,KITAI T, HAZEN SL. Gut microbiota in cardiovascular health and disease[J]. Circ Res, 201 7,120(7):1183-1196.
[14] PRATAS D, SILVA RM, PINHO AJ, et al.An alignment-free method to find and visualise rearrangements between pairs of DNA sequences[J]. Sci Rep,2015, 5:10203.
[15]杨波,铁宝霞,蔡小玲,等.肠道微生态研究方法及应用研究进展[J].广西医学,2018, 40(10):1219-1221.
[16]梁跃斌,李彬春,李艳琴.基于宏基因组学方法挖掘新型α-L-鼠-李糖苷酶资源[J].中国生物化学与分子生物学报,2017,31(1):66-72.
[17] HOFF KJ, TECH M, LINGNER T, et al.Gene prediction in metagenomic fragments:a large scale machine learning approach[J]. BMC Bioinformatics, 2008, 9:21 7.
[18] GELLER LT, BARZILYROKNI M,DANION T, et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine[J]. Science, 2017,357(6356):1156-1160.
[19] ZITVOGEL L, DAILLERE R, ROBERTI MP, et al.Anticancer effects of the microbiome and its products[J]. Nat Rev Microbiol,2017, 15(8):465-478.
[20] LIU SZ, CHEN WQ, WANG N, et al.Dietary factors and risk of pancreatic cancer:a multi-centre case-control study in ChinaU]. Asian Pac J Cancer Prev, 2014, 1 5(1 8):7947-7950.
[21] WU QJ, WU L, ZHENG LQ, et al.Consumption of fruit and vegetables reduces risk of pancreatic cancer:evidence from epidemiological studies[J]. Eur J Cancer Prev, 2016,25(3):1 96-205.
[22] BAO Y, NG K, WOLPIN BM, et al.Predited vitamin D status and pancreatic cancer risk in two prospective cohort studies[J]. Brit J Cancer, 201 0, 1 02(9):1422-1 427.
[23] CHUANG SC, GALLO V, MICHAUD D,et al. Exposure to environmental tobacco smoke in childhood and incidence of cancer in adulthood in never smokers in the European prospective investigation into cancer and nutrition[J]. Cancer Cause Control,2011,22(3):487-494.
[24]金玲玲,王晓林,曹仕琼.外泌体与胰腺癌化疗耐药的研究进展[J].实用医学杂志,2018, 34(5):860-863.
[25] HUSSAIN SP, HOFSETH LJ, HARRIS CC.Radical causes of cancer[J], Nat Rev Cancer, 2003, 3(4):276-285.
[26] SIVAN A, CORRALES L, HUBERT N,et al. Commensal bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy[J].Science, 2015, 350(6264):1084-1089.
[27] FEI N, ZHAO L. An opportunistic pathogen isolated from the gut of an obese human causes obesityin germfree mice[J]. ISME J, 2013,7(4):880-884.
[28] HAKKAK R, KOROURIAN S, FOLEY SL,et al. Assessment of gut microbiota populations in lean and obese Zucker rats[J]. PLoS One, 201 7, 1 2(7):e0181451.
[29] BEYER G, D'HAESE JG, ORMANNS S, et al.Chronic pancreatitis and pancreatic cancertumor risk and screening[J]. Deut Med Wochenschr,2018, 143(12):895-906.
[30] SONG S, WANG B, ZHANG X, et al.Long-term diabetes mellitus is associated with an increased risk of pancreatic cancer:a meta-analysis[J].PLoS One, 201 5, 1 0(7):e0134321.
[31] LARSEN N, VOGENSEN FK, VAN DEN BERG FW, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults[J].PLoS One, 2010, 5(2):e9085.
[32] CRUZ NG, SOUSA LP, SOUSA MO, et al.The linkage between inflammation and type 2 diabetes mellitus[J]. Diabetes Res Clin Pract, 201 3, 99(2):85-92.
[33] KOMURA T, SAKAI Y, HONDA M, et al.CD14+monocytes are vulnerable and functionally impaired under endoplasmic reticulum stress in patients with type 2diabetes[J]. Diabetes, 2010, 59(3):634-643.
[34] RIDLON J M, KANG DJ, HYLEMON PB,et al. Gut microbiota, cirrhosis, and alcohol regulate bile acid metabolism in the gut[J]. Digest Dis, 201 5,33(3):338-345.
[35] PESIC M, GRETEN FR. Inflammation and cancer:tissue regeneration gone awry[J]. Curr Opin Cell Biol, 2016,43:55-61.
[36] KUNDU JK, SURH YJ. Inflammation:gearing the journey to cancer[J]. Mutat Res, 2008, 659(1):1 5-30.
[37] HUMPHRIS J L, JOHNS AL, SIMPSON SH,et al. Clinical and pathologic features of familial pancreatic cancer[J]. Cancer,2015, 120(23):3669-3675.
[38] ZAMBIRINIS CP, PUSHALKAR S,SAXENA D, et al. Pancreatic cancer,inflammation, and microbiome.[J].CancerJ, 2014, 20(3):195-202.
[39] HOUTEN SM, WATANABE M, AUWERX J.Endocrine functions of bile acids[J].EMBO J, 2014, 25(7):141 9-1425.
[40] TUCKER ON, DAN N EN BERG AJ,YANG EK, et al. Bile acids induce cyclooxyoenase-2 expression inhuman pancreatic cancer cell lines[J].Carcinogenesis, 2004, 25(3):419-423.
[41]刘昌,吕毅,王浩华,等.胆汁酸对人胰腺癌细胞的毒性作用[J].医学争鸣,2003, 24(22):2084-2086.
[42]李淑玲,李闻.胆汁酸与肠道微生态的研究进展[J].胃肠病学和肝病学杂志,2018,27(4):466-470.
[43]王维斌,董良博,赵邦博,等.法尼醇X受体表达与胰腺癌患者预后及病理分期相关[J].基础医学与临床,2018,38(3):394-399.
[44] TORRES PJ, FLETCHER EM, GIBBONS SM,et al. Characterization of the salivary microbiome in patients with pancreatic cancer[J]. PeerJ, 2015, 3(11):e1373.
[45] SHADNOUSH M, HOSSEINI RS,KHALILNEZHAD A, et al. Effects of probiotics on gut microbiota in patients with inflammatory bowel disease:A double-blind, placebocontrolled clinical trial[J]. Korean J Gastroenterol, 201 5, 65(4):21 5-221.
[46] BOLDEN JE, PEART MJ, JOHNSTONE RW.Anticancer activities of histone deacetylase inhibitors[J]. Nat Rev Drug Discov, 2006, 5(9):769-784.
[47] CORRA S, KAZAKOFF K, MOGAKI M, et al.Modification of antigen expression in human and hamster pancreatic cancer cell lines induced by sodium butyrate[J]. Teratog Carcinog Mutagen,1993, 13(5):199-21 5.
[48] FARROW B,RYCHAHOU P,O'CONNOR KL,et al. Butyrate inhibits pancreatic cancer invasion[J].J Gastrointest Surg, 2003,7(7):864-870.
[49]仓晓风,万荣.肠道微生态与胰腺疾病[J].现代消化及介入诊疗,2017,22(1):160-162.
[50]王艺,王理伟.胰腺癌患者免疫状态及免疫治疗进展[J].肿瘤,201 8,38(6):610-616.
[51] HORAI R, ZARATE-BLADES CR,DILLENBURG-PILLA P, et al.Microbiota-dependent activation of an autoreactive T cell receptor provokes autoimmunity in an immunologically privileged site[J]. Immunity, 2015,43(2):343-353.
[52] VETIZOU M, PITT J M, DAILLERE R,et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota[J]. Science, 2015,350(6264):1 079-1084.