肠道菌群失衡在肝癌发生发展中的影响机制及益生菌对肝癌的预防作用

高艳颖; 向慧玲; 梁静; 韩涛; 张旭

doi:10.3969/j.issn.1001-5256.2022.03.042

肠道菌群失衡在肝癌发生发展中的影响机制及益生菌对肝癌的预防作用

DOI: 10.3969/j.issn.1001-5256.2022.03.042

天津市第三中心医院，天津市重症疾病体外生命支持重点实验室，天津市人工细胞工程技术研究中心，天津市肝胆疾病研究所，天津 300170

基金项目:

天津科技重大专项与工程重大疾病防治 (19ZXDBSY00030)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：高艳颖负责课题设计，资料分析，撰写论文；张旭负责查阅文献确定研究方向以及参考文献的分类整理；向慧玲、梁静、韩涛负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
梁静，haolele77@sina.com

计量
- 文章访问数: 636
- HTML全文浏览量: 174
- PDF下载量: 64
- 被引次数: 0
出版历程
- 收稿日期: 2021-07-21
- 录用日期: 2021-08-30
- 出版日期: 2022-03-20

Mechanism of intestinal flora imbalance in the development and progression of liver cancer and the role of probiotics in preventing liver cancer

Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin Institute of Hepatobiliary Disease, Tianjin Third Central Hospital, Tianjin 300170, China

Research funding:

Tianjin Science and Technology Major Project and Engineering of Critical Disease Prevention and Control (19ZXDBSY00030)

More Information

Corresponding author: LIANG Jing, haolele77@sina.com(ORCID: 0000-0001-5114-9030)

摘要

摘要: 肠道菌群失衡在肝癌的发生发展过程中起到一定作用，而益生菌对肝癌具有一定影响，二者均是临床的研究热点。本文介绍了肠道菌群失衡在肝癌发病中的作用机制以及益生菌对肝癌的预防效果。肠道菌群失衡可通过激活Toll样受体4、调控代谢物水平、产生内毒素、诱发细菌移位和小肠细菌过度增长等机制参与肝癌的病理过程；而益生菌可通过维持肝肠循环、增强免疫功能、促进肠道益生菌繁殖、降低致癌物毒性等机制发挥有效预防肝癌的作用，其可作为后续临床肝癌预防工作的重点方向进行深入研究。
- 肝肿瘤 /
- 胃肠道微生物组 /
- 鼠李糖乳杆菌
Abstract: Intestinal flora imbalance plays a certain role in the development and progression of liver cancer, while probiotics have a certain impact on liver cancer, both of which are the focus of clinical research. This article introduces the mechanism of action of intestinal flora imbalance in the pathogenesis of liver cancer and the preventive effect of probiotics against liver cancer. Intestinal flora imbalance can participate in the pathological process of liver cancer by activating Toll-like receptor 4, regulating the level of metabolites, producing endotoxin, and inducing bacterial translocation and intestinal bacterial overgrowth, while probiotics can effectively prevent liver cancer by maintaining enterohepatic circulation, enhancing immune function, promoting the reproduction of intestinal probiotics, and reducing the toxicity of carcinogens, which can be further studied as the focus of subsequent liver cancer prevention in clinical practice.
- Liver Neoplasms /
- Gastrointestinal Microbiome /
- Lactobacillus rhamnosus

HTML全文

参考文献(34)

[1]	RICE DR, HYER JM, DIAZ A, et al. End-of-life hospice use and medicare expenditures among patients dying of hepatocellular carcinoma[J]. Ann Surg Oncol, 2021, 28(9): 5414-5422. DOI: 10.1245/s10434-021-09606-7.
[2]	GERBES A, ZOULIM F, TILG H, et al. Gut roundtable meeting paper: Selected recent advances in hepatocellular carcinoma[J]. Gut, 2018, 67(2): 380-388. DOI: 10.1136/gutjnl-2017-315068.
[3]	SCHWABE RF, GRETEN TF. Gut microbiome in HCC -Mechanisms, diagnosis and therapy[J]. J Hepatol, 2020, 72(2): 230-238. DOI: 10.1016/j.jhep.2019.08.016.
[4]	ZHANG Q, WANG XB. The role of gut microbiota in the pathogenesis of portal hypertension[J]. J Clin Hepatol, 2020, 36(3): 673-676. DOI: 10.3969/j.issn.1001-5256.2020.03.044. 张群, 王宪波. 肠道菌群在门静脉高压发病机制中的作用[J]. 临床肝胆病杂志, 2020, 36(3): 673-676. DOI: 10.3969/j.issn.1001-5256.2020.03.044.
[5]	GIUFFRÈ M, CAMPIGOTTO M, CAMPISCIANO G, et al. A story of liver and gut microbes: How does the intestinal flora affect liver disease? A review of the literature[J]. Am J Physiol Gastrointest Liver Physiol, 2020, 318(5): g889-g906. DOI: 10.1152/ajpgi.00161.2019.
[6]	LIU Y, ZHANG YY, ZOU Y, et al. Association between intestinal microecology and spontaneous bacterial peritonitis[J]. J Clin Hepatol, 2021, 37(2): 425-428. DOI: 10.3969/j.issn.1001-5256.2021.02.037. 刘玉, 张宇一, 邹颖, 等. 肠道微生态与自发性细菌性腹膜炎的关系[J]. 临床肝胆病杂志, 2021, 37(2): 425-428. DOI: 10.3969/j.issn.1001-5256.2021.02.037.
[7]	ZHENG W, ZHAO P, ZHANG YH, et al. Metagenomic analysis on characteristics of intestinal flora of patients with primary liver cancer[J/CD]. Chin J Exp Clin Infect Dis (Electronic Edition), 2021, 15(3): 149-157. DOI: 10.3877/cma.j.issn.1674-1358.2021.03.002. 郑微, 赵鹏, 张永宏, 等. 宏基因组测序技术分析原发性肝癌患者肠道菌群特征[J/CD]. 中华实验和临床感染病杂志(电子版), 2021, 15(3): 149-157. DOI: 10.3877/cma.j.issn.1674-1358.2021.03.002.
[8]	REN Z, LI A, JIANG J, et al. Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma[J]. Gut, 2019, 68(6): 1014-1023. DOI: 10.1136/gutjnl-2017-315084.
[9]	PONZIANI FR, BHOORI S, CASTELLI C, et al. Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in nonalcoholic fatty liver disease[J]. Hepatology, 2019, 69(1): 107-120. DOI: 10.1002/hep.30036.
[10]	XIN HR, LI X, SUN RF, et al. Endotoxin and intestinal microflora in patients with hepatocellular carcinoma[J]. Chin J Gen Surg, 2019, 34(8): 686-688. DOI: 10.3670.cma.j.issn.1007-631X.2019.08.011. 辛海荣, 李喜, 孙瑞芳, 等. 原发性肝癌患者内毒素与肠道菌群变化的相关性研究[J]. 中华普通外科杂志, 2019, 34(8): 686-688. DOI: 10.3670.cma.j.issn.1007-631X.2019.08.011.
[11]	PONZIANI FR, PUTIGNANI L, PARONI STERBINI F, et al. Influence of hepatitis C virus eradication with direct-acting antivirals on the gut microbiota in patients with cirrhosis[J]. Aliment Pharmacol Ther, 2018, 48(11-12): 1301-1311. DOI: 10.1111/apt.15004.
[12]	SHEN W, REN HT, RUAN B. Association between hepatitis B liver cirrhosis and intestinal flora[J]. J Clin Intern Med, 2020, 37(8): 557-560. DOI: 10.3969/j.issn.1001-9057.2020.08.007. 沈伟, 任浩堂, 阮冰. 浅论乙型病毒性肝炎肝硬化与肠道菌群的关系[J]. 临床内科杂志, 2020, 37(8): 557-560. DOI: 10.3969/j.issn.1001-9057.2020.08.007.
[13]	PURI P, LIANGPUNSAKUL S, CHRISTENSEN JE, et al. The circulating microbiome signature and inferred functional metagenomics in alcoholic hepatitis[J]. Hepatology, 2018, 67(4): 1284-1302. DOI: 10.1002/hep.29623.
[14]	CHEN LP, HUANG J, CHENG JL. Toll-like receptors-mediated innate immune responses in HBV infection[J]. Chin J Microbiol Immunol, 2018, 38(8): 635-640. DOI: 10.3760/cma.j.issn.0254-5101.2018.08.013. 陈丽萍, 黄俊, 程计林. Toll样受体介导的固有免疫应答在HBV感染中的研究进展[J]. 中华微生物学和免疫学杂志, 2018, 38(8): 635-640. DOI: 10.3760/cma.j.issn.0254-5101.2018.08.013.
[15]	WANG L, WAN YY. The role of gut microbiota in liver disease development and treatment[J]. Liver Res, 2019, 3(1): 3-18. DOI: 10.1016/j.livres.2019.02.001.
[16]	SONG XL, GU J, LIU YB. Research advance in the influence of dysbacteriosis on hepatobiliary malignancy[J]. Chin J Dig Surg, 2020, 19(12): 1336-1340. DOI: 10.3760/cma.j.cn115610-20201019-00663. 宋晓玲, 顾钧, 刘颖斌. 菌群紊乱对肝胆肿瘤影响的研究进展[J]. 中华消化外科杂志, 2020, 19(12): 1336-1340. DOI: 10.3760/cma.j.cn115610-20201019-00663.
[17]	CHEN M, DAO YX, WANG J. Research progress on the correlation between intestinal flora and primary liver cancer[J]. Chin J Clin Oncol, 2020, 47(18): 961-964. DOI: 10.3969/j.issn.1000-8179.2020.18.765. 陈默, 刀永祥, 王君. 肠道菌群与原发性肝癌相关性的研究进展[J]. 中国肿瘤临床, 2020, 47(18): 961-964. DOI: 10.3969/j.issn.1000-8179.2020.18.765.
[18]	NAKAMOTO N, KANAI T. Role of toll-like receptors in immune activation and tolerance in the liver[J]. Front Immunol, 2014, 5: 221. DOI: 10.3389/fimmu.2014.00221.
[19]	GIANNELLI V, DI GREGORIO V, IEBBA V, et al. Microbiota and the gut-liver axis: Bacterial translocation, inflammation and infection in cirrhosis[J]. World J Gastroenterol, 2014, 20(45): 16795-16810. DOI: 10.3748/wjg.v20.i45.16795.
[20]	FAN SX, WANG J, LI Q, et al. Mechanism of gut-microbiota-liver axis in the pathogenesis of intestinal failure-associated liver disease[J]. Chin J Gastrointestinal Surg, 2021, 24(1): 94-100. DOI: 10.3760/cma.j.cn.441530-20201009-00550. 范圣先, 王剑, 李强, 等. 肠-菌-肝轴及其在肠衰竭相关性肝损害发生发展中的作用[J]. 中华胃肠外科杂志, 2021, 24(1): 94-100. DOI: 10.3760/cma.j.cn.441530-20201009-00550.
[21]	LI TT, ZHU D, MOU T, et al. IL-37 induces autophagy in hepatocellular carcinoma cells by inhibiting the PI3K/AKT/mTOR pathway[J]. Mol Immunol, 2017, 87: 132-140. DOI: 10.1016/j.molimm.2017.04.010.
[22]	BRANDI G, DE LORENZO S, CANDELA M, et al. Microbiota, NASH, HCC and the potential role of probiotics[J]. Carcinogenesis, 2017, 38(3): 231-240. DOI: 10.1093/carcin/bgx007.
[23]	WANG Y, LIU ZY, CHEN GR. Progress in studies of endotoxin receptor and anti-endotoxin[J]. Chin Arch Tradit Chin Med, 2016, 34(10): 2367-2370. DOI: 10.13193/j.issn.1673-7717.2016.10.018. 王祎, 刘哲音, 陈桂荣. 内毒素受体及抗内毒素的研究进展[J]. 中华中医药学刊, 2016, 34(10): 2367-2370. DOI: 10.13193/j.issn.1673-7717.2016.10.018.
[24]	WEI XM, ZHANG ML, ZHANG J, et al. Distribution of pathogens causing nosocomial infections in liver cancer patients undergoing intervention chemotherapy and influencing factors[J]. Chin J Nosocomiol, 2018, 28(17): 2621-2624. DOI: 10.11816/cn.ni.2018-173371. 韦小妹, 张名林, 张金, 等. 肝癌介入化疗患者医院感染的病原菌分布及影响因素分析[J]. 中华医院感染学杂志, 2018, 28(17): 2621-2624. DOI: 10.11816/cn.ni.2018-173371.
[25]	WU FF, PENG YZ. Gut microbiota at different stages of HBV infection[J]. J Pract Med, 2017, 33(12): 2032-2035. DOI: 10.3969/j.issn.1006-5725.2017.12.037. 伍菲凡, 彭永正. 乙型肝炎病毒不同感染状态下的肠道菌群结构[J]. 实用医学杂志, 2017, 33(12): 2032-2035. DOI: 10.3969/j.issn.1006-5725.2017.12.037.
[26]	SUN L, DAI JJ, HU WF, et al. Expression of toll-like receptors in hepatic cirrhosis and hepatocellular carcinoma[J]. Genet Mol Res, 2016, 15(2): gmr7419. DOI: 10.4238/gmr.15027419.
[27]	MA C, HAN M, HEINRICH B, et al. Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells[J]. Science, 2018, 360(6391): eaan5931. DOI: 10.1126/science.aan5931.
[28]	HARTMANN N, KRONENBERG M. Cancer immunity thwarted by the microbiome[J]. Science, 2018, 360(6391): 858-859. DOI: 10.1126/science.aat8289.
[29]	LIU JL, QIN B, ZHENG ZD. Advances in gut microbiota and hepatocellular carcinoma[J]. Chin J Cancer Biother, 2018, 25(11): 1185-1190. DOI: 10.3872/j.issn.1007-385x.2018.11.018. 刘军灵, 秦斌, 郑振东. 肠道微生物稳态与肝癌关系的研究进展[J]. 中国肿瘤生物治疗杂志, 2018, 25(11): 1185-1190. DOI: 10.3872/j.issn.1007-385x.2018.11.018.
[30]	WANG XP, SHI YQ. Berberine combined probiotic treatment clinical observation of non-alcoholic fatty liver disease[J]. Chin J Ctrl Endem Dis, 2016, 31(9): 1048. https://www.cnki.com.cn/Article/CJFDTOTAL-DYBF201609048.htm 王小平, 石永强. 小檗碱联合益生菌治疗非酒精性脂肪肝的临床观察[J]. 中国地方病防治杂志, 2016, 31(9): 1048. https://www.cnki.com.cn/Article/CJFDTOTAL-DYBF201609048.htm
[31]	CEN RF, WU TF, HUANG SJ, et al. Clinic trial of bifid-triple viable capsule combined with reduced glutathione injection in the treatment of primary liver cancer patients after transcatheter hepatic arterial chemoembolization[J]. Chin J Clin Pharmacol, 2016, 32(24): 2247-2249. DOI: 10.13699/j.cnki.1001-6821.2016.24.010. 岑荣飞, 吴田方, 黄时界, 等. 双歧三联活菌胶囊联合还原型谷胱甘肽注射剂用于原发性肝癌患者化疗栓塞术后的临床研究[J]. 中国临床药理学杂志, 2016, 32(24): 2247-2249. DOI: 10.13699/j.cnki.1001-6821.2016.24.010.
[32]	HUANG W, CHANG J, WANG P, et al. Effect of the combined compound probiotics with mycotoxin-degradation enzyme on detoxifying aflatoxin B1 and zearalenone[J]. J Toxicol Sci, 2018, 43(6): 377-385. DOI: 10.2131/jts.43.377.
[33]	PANG BY, JIANG YF, LI Y, et al. Relationship between intestinal flora and intestinal tumors[J]. J Pract Med, 2017, 33(20): 3488-3491. DOI: 10.3969/j.issn.1006-5725.2017.20.041. 庞冰玉, 姜雅菲, 李颖, 等. 肠道菌群与肠道外肿瘤关系的研究进展[J]. 实用医学杂志, 2017, 33(20): 3488-3491. DOI: 10.3969/j.issn.1006-5725.2017.20.041.
[34]	SUN Y, HUANG Y, YE F, et al. Effects of probiotics on glycemic control and intestinal dominant flora in patients with type 2 diabetes mellitus: A protocol for systematic review and meta-analysis[J]. Medicine (Baltimore), 2020, 99(46): e23039. DOI: 10.1097/MD.0000000000023039.