肠道菌群对乳腺癌发生发展的影响及其治疗应用的研究进展

doi:10.13481/j.1671-587X.20240435

Abstract

Abstract:

The incidence of breast cancer is increasing year by year， and its pathogenesis is highly complex. The dysregulation of gut microbiota function is closely related to the occurrence and development of breast cancer. The estrogen levels through enterohepatic circulation is regulated by β-glucuronidase produced by the gut microbiota， thereby influencing the occurrence and development of hormone receptor-positive breast cancer and leading to tamoxifen resistance. The metabolites from the gut microbiota， such as short-chain fatty acids （SCFAs） and lithocholic acid （LCA）， can participate in regulating the tumor cell cycles and cell proliferation. The colonization of gut microbiota maintains the integrity of the intestinal barrier and regulates the anti-tumor immunity mediated by T lymphocytes. Maintaining gut microbiota homeostasis can enhance the efficacy of tumor chemotherapy and immunotherapy and reduce the adverse reactions in anti-tumor treatments. The targeted action of engineered probiotics in immunotherapy can improve the precision of drug treatment. The effect of gut microbiota on radiotherapy is not yet clear， but regulating gut microbiota can aid in the treatment of radiation enteritis. This review discusses the correlation and effect of gut microbiota on breast cancer and analyzes its role in the treatment of breast cancer.

Key words: Breast neoplasm, Gut microbiota, Estrogen metabolism, Immunoregulation

CLC Number:

R737.9

Xiaomin FU,Jianling JIA,Yanhong DOU,Wenyong REN,Aiping SHI. Research progress in effect of intestinal flora on occurrence and development of breast cancer and its therapeutic application[J].Journal of Jilin University(Medicine Edition), 2024, 50(4): 1182-1188.

References 52

1	SUNG H， FERLAY J， SIEGEL R L， et al. Global cancer statistics 2020： GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries［J］.CA Cancer J Clin， 2021，71（3）：209-249.
2	ARNOLD M， MORGAN E， RUMGAY H， et al. Current and future burden of breast cancer： global statistics for 2020 and 2040［J］. Breast， 2022， 66： 15-23.
3	WU M H， CHOU Y C， CHOU W Y， et al. Relationships between critical period of estrogen exposure and circulating levels of insulin-like growth factor-Ⅰ （IGF-Ⅰ） in breast cancer： evidence from a case-control study［J］. Int J Cancer， 2010， 126（2）： 508-514.
4	FU A K， YAO B Q， DONG T T， et al. Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer［J］. Cell， 2022， 185（8）： 1356-1372.e26.
5	NEJMAN D， LIVYATAN I， FUKS G， et al. The human tumor microbiome is composed of tumor type-specific intracellular bacteria［J］.Science，2020，368（6494）： 973-980.
6	PARIDA S， WU S G， SIDDHARTH S， et al. A procarcinogenic colon microbe promotes breast tumorigenesis and metastatic progression and concomitantly activates Notch and β-catenin axes［J］. Cancer Discov， 2021， 11（5）： 1138-1157.
7	XUAN C Y， SHAMONKI J M， CHUNG A， et al. Microbial dysbiosis is associated with human breast cancer［J］. PLoS One， 2014， 9（1）： e83744.
8	TERRISSE S， DEROSA L， IEBBA V， et al. Intestinal microbiota influences clinical outcome and side effects of early breast cancer treatment［J］. Cell Death Differ， 2021， 28（9）： 2778-2796.
9	BAEK A E. Bacteria benefit tumor cells［J］. Sci Signal， 2022， 15（729）： eabq4492.
10	WU A H， TSENG C， VIGEN C， et al. Gut microbiome associations with breast cancer risk factors and tumor characteristics： a pilot study［J］. Breast Cancer Res Treat， 2020， 182（2）： 451-463.
11	GRUBER C J， TSCHUGGUEL W， SCHNEEBERGER C， et al. Production and actions of estrogens［J］. N Engl J Med， 2002， 346（5）： 340-352.
12	GRAY J M， RASANAYAGAM S， ENGEL C， et al. State of the evidence 2017： an update on the connection between breast cancer and the environment［J］. Environ Health， 2017， 16（1）： 94.
13	PARIDA S， SHARMA D. The microbiome-estrogen connection and breast cancer risk［J］.Cells，2019，8（12）： 1642.
14	ADLERCREUTZ H， MARTIN F. Biliary excretion and intestinal metabolism of progesterone and estrogens in man［J］. J Steroid Biochem， 1980， 13（2）： 231-244.
15	KWA M， PLOTTEL C S， BLASER M J， et al. The intestinal microbiome and estrogen receptor-positive female breast cancer［J］.J Natl Cancer Inst，2016，108（8）： djw029.
16	HU S W， DING Q Y， ZHANG W， et al. Gut microbial beta-glucuronidase： a vital regulator in female estrogen metabolism［J］. Gut Microbes， 2023， 15（1）： 2236749.
17	MOORE S C， MATTHEWS C E， OU-SHU X， et al. Endogenous estrogens， estrogen metabolites， and breast cancer risk in postmenopausal Chinese women［J］. J Natl Cancer Inst， 2016， 108（10）：103.
18	ROSENBERG L， BETHEA T N， VISCIDI E， et al. Postmenopausal female hormone use and estrogen receptor-positive and-negative breast cancer in African American women［J］.J Natl Cancer Inst，2016，108（4）： 361.
19	ZACKSENHAUS E， SHRESTHA M， LIU J C， et al. Mitochondrial OXPHOS induced by RB1 deficiency in breast cancer： implications for anabolic metabolism， stemness，and metastasis［J］.Trends Cancer，2017，3（11）： 768-779.
20	SOTGIA F， LISANTI M P. Mitochondrial mRNA transcripts predict overall survival， tumor recurrence and progression in serous ovarian cancer： companion diagnostics for cancer therapy［J］.Oncotarget，2017，8（40）： 66925-66939.
21	REDDY B S， HANSON D， MANGAT S， et al. Effect of high-fat， high-beef diet and of mode of cooking of beef in the diet on fecal bacterial enzymes and fecal bile acids and neutral sterols［J］. J Nutr， 1980， 110（9）： 1880-1887.
22	MCINTOSH F M， MAISON N， HOLTROP G， et al. Phylogenetic distribution of genes encoding β-glucuronidase activity in human colonic bacteria and the impact of diet on faecal glycosidase activities［J］. Environ Microbiol， 2012， 14（8）： 1876-1887.
23	DABEK M， MCCRAE S I， STEVENS V J， et al. Distribution of beta-glucosidase and beta-glucuronidase activity and of beta-glucuronidase gene gus in human colonic bacteria［J］.FEMS Microbiol Ecol，2008，66（3）： 487-495.
24	REDDY B S， ENGLE A， SIMI B， et al. Effect of dietary fiber on colonic bacterial enzymes and bile acids in relation to colon cancer［J］. Gastroenterology， 1992， 102（5）： 1475-1482.
25	ADLERCREUTZ H， MARTIN F， PULKKINEN M， et al. Intestinal metabolism of estrogens［J］. J Clin Endocrinol Metab， 1976， 43（3）： 497-505.
26	XIE W J， HUANG Y F， XIE W L， et al. Bacteria peptidoglycan promoted breast cancer cell invasiveness and adhesiveness by targeting toll-like receptor 2 in the cancer cells［J］. PLoS One， 2010， 5（5）： e10850.
27	MIKÓ E， VIDA A， KOVÁCS T， et al. Lithocholic acid， a bacterial metabolite reduces breast cancer cell proliferation and aggressiveness［J］. Biochim Biophys Acta Bioenerg， 2018， 1859（9）： 958-974.
28	PARK H S， HAN J H， PARK J W， et al. Sodium propionate exerts anticancer effect in mice bearing breast cancer cell xenograft by regulating JAK2/STAT3/ROS/p38 MAPK signaling［J］.Acta Pharmacol Sin，2021，42（8）： 1311-1323.
29	MA H， YU Y， WANG M M， et al. Correlation between microbes and colorectal cancer： tumor apoptosis is induced by sitosterols through promoting gut microbiota to produce short-chain fatty acids［J］. Apoptosis， 2019， 24（1/2）： 168-183.
30	DONALDSON G P， LADINSKY M S， YU K B，et al. Gut microbiota utilize immunoglobulin A for mucosal colonization［J］. Science， 2018， 360（6390）： 795-800.
31	YANG Y B， LI L L， XU C J， et al. Cross-talk between the gut microbiota and monocyte-like macrophages mediates an inflammatory response to promote colitis-associated tumourigenesis［J］. Gut， 2020， 70（8）： 1495-1506.
32	MA J， SUN L Q， LIU Y， et al. Alter between gut bacteria and blood metabolites and the anti-tumor effects of Faecalibacterium prausnitzii in breast cancer［J］. BMC Microbiol， 2020， 20（1）： 82.
33	WANG H， RONG X Y， ZHAO G， et al. The microbial metabolite trimethylamine N-oxide promotes antitumor immunity in triple-negative breast cancer［J］. Cell Metab， 2022， 34（4）： 581-594.
34	LI Y Y， DONG B B， WU W， et al. Metagenomic analyses reveal distinct gut microbiota signature for predicting the neoadjuvant chemotherapy responsiveness in breast cancer patients［J］. Front Oncol， 2022， 12： 865121.
35	ZHANG Y Y， ZHANG Z M. The history and advances in cancer immunotherapy： understanding the characteristics of tumor-infiltrating immune cells and their therapeutic implications［J］. Cell Mol Immunol， 2020， 17（8）： 807-821.
36	WU S Y， XU Y， CHEN L， et al. Combined angiogenesis and PD-1 inhibition for immunomodulatory TNBC： concept exploration and biomarker analysis in the FUTURE-C-Plus trial［J］.Mol Cancer，2022，21（1）： 84.
37	MAGER L F， BURKHARD R， PETT N， et al. Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy［J］. Science， 2020， 369（6510）： 1481-1489.
38	ROUTY B， CHATELIER E L， DEROSA L， et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors［J］. Science， 2018， 359（6371）： 91-97.
39	VÉTIZOU M， PITT J M， DAILLÈRE R， et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota［J］. Science， 2015， 350（6264）： 1079-1084.
40	GURBATRI C R， LIA I， VINCENT R， et al. Engineered probiotics for local tumor delivery of checkpoint blockade nanobodies［J］. Sci Transl Med， 2020， 12（530）： eaax0876.
41	DAILLÈRE R， VÉTIZOU M， WALDSCHMITT N， et al. Enterococcus hirae and barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects［J］. Immunity， 2016， 45（4）： 931-943.
42	LV Z， LIU R D， SU K Q， et al. Acupuncture ameliorates breast cancer-related fatigue by regulating the gut microbiota-gut-brain axis［J］. Front Endocrinol， 2022， 13： 921119.
43	BULTMAN S J. Emerging roles of the microbiome in cancer［J］. Carcinogenesis， 2014， 35（2）： 249-255.
44	LOZUPONE C A， STOMBAUGH J I， GORDON J I， et al. Diversity， stability and resilience of the human gut microbiota［J］. Nature， 2012， 489（7415）： 220-230.
45	张晨宇，单忠艳. 肠道菌群及其代谢产物在 2 型糖尿病中的作用研究进展［J］. 中国实用内科杂志，2023， 43（8）： 682-687.
46	APETOH L， GHIRINGHELLI F， TESNIERE A，et al.Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy［J］. Nat Med， 2007， 13（9）： 1050-1059.
47	SHIAO S L， KERSHAW K M， LIMON J J， et al. Commensal bacteria and fungi differentially regulate tumor responses to radiation therapy［J］. Cancer Cell， 2021， 39（9）： 1202-1213.e6.
48	URIBE-HERRANZ M， RAFAIL S， BEGHI S， et al. Gut microbiota modulate dendritic cell antigen presentation and radiotherapy-induced antitumor immune response［J］. J Clin Invest， 2020， 130（1）： 466-479.
49	MITRA A， GROSSMAN BIEGERT G W， DELGADO A Y， et al. Microbial diversity and composition is associated with patient-reported toxicity during chemoradiation therapy for cervical cancer［J］. Int J Radiat Oncol Biol Phys， 2020， 107（1）： 163-171.
50	REIS FERREIRA M， ANDREYEV H J N， MOHAMMED K， et al. Microbiota- and radiotherapy-induced gastrointestinal side-effects （MARS） study： a large pilot study of the microbiome in acute and late-radiation enteropathy［J］.Clin Cancer Res，2019，25（21）： 6487-6500.
51	LIU J， LIU C， YUE J B. Radiotherapy and the gut microbiome： facts and fiction［J］. Radiat Oncol， 2021， 16（1）： 9.
52	CUI M， XIAO H W， LUO D， et al. Circadian rhythm shapes the gut microbiota affecting host radiosensitivity［J］. Int J Mol Sci， 2016， 17（11）： 1786.

[1]	Xue WEI,Xue WEN,Xiao XIE,Yueyuan WANG,Dan HUANG,Ming YANG. Expression levels and imprinting status of lncRNA H19 and IGF2 genes in breast cancer tissue [J]. Journal of Jilin University(Medicine Edition), 2024, 50(4): 1109-1115.
[2]	Can ZHANG,Yan CHEN. Research progress in pathogenesis and treatment of gastrointestinal motility disorders in Parkinson’s disease [J]. Journal of Jilin University(Medicine Edition), 2024, 50(1): 280-287.
[3]	Yuesheng ZHAO,Zubin LI,Haiou LIU,Kunlin TAO,Qihai ZHAO,Na LI. Inhibitory effect of silencing CDKL1 gene on proliferation and invasion of breast cancer MCF-7 cells by regulating PTEN/Akt/mTOR signaling pathway [J]. Journal of Jilin University(Medicine Edition), 2023, 49(5): 1234-1242.
[4]	Changchun MU,Chunji QUAN,Quanjin JIN,Zhengri PIAO. Expression of thymosin beta4 in breast cancer tissue and its effect on migration and invasion of breast cancer cells [J]. Journal of Jilin University(Medicine Edition), 2023, 49(4): 890-895.
[5]	Xiuyan YU,Ting LI,Zhanjie CONG,Wenlong WANG,Xiaowei ZHANG,Xuefeng WU. Combined detection of hMAM, SBEM and CEACAM19 mRNA in peripheral blood of breast cancer patients and its clinical significance [J]. Journal of Jilin University(Medicine Edition), 2022, 48(1): 195-202.
[6]	Xiuyan YU,Chunying TIAN,Xiaowei ZHANG,Xuefeng WU. Clinical significances of serum levels of SBEM, hMAM and CEACAM19 in early diagnosis of breast cancer [J]. Journal of Jilin University(Medicine Edition), 2021, 47(6): 1518-1525.
[7]	Yang YU,Sainan LIU,Yunkai LIU,Yong LI,Yichun QIAO,Yi CHENG. Bioinformatic analysis on expression characteristics of PRPS2 and its relationship with prognosis of breast cancer [J]. Journal of Jilin University(Medicine Edition), 2021, 47(5): 1229-1236.
[8]	Pei GONG, Jingran LIU, Shimin ZHAO, Yuzhen WANG, Jiming XIE. Inhibitory effect of MCM10 silencing on proliferation of breast cancer MDA-MB-231 cells and its mechanism [J]. Journal of Jilin University(Medicine Edition), 2021, 47(3): 652-659.
[9]	Qing WANG,Siqi XIE,Kai ZHENG,Yiyin TANG,Hongwan LI,Hengyu ZHANG,Mingjian TAN,Lei PENG,Dequan LIU,Shicong TANG. Detection of serum vitamin-B levels in breast cancer patients receiving different chemotherapy regimens and its clinical significance [J]. Journal of Jilin University(Medicine Edition), 2021, 47(3): 724-730.
[10]	Haoxuan TANG,Nanfeng MENG,Meiling DU,Wei WANG,Tao HE. Inhibitory effect of new VEGF monoclonal antibody combined with all-trans retinoic acid on proliferation of breast cancer MCF-7 cells [J]. Journal of Jilin University(Medicine Edition), 2021, 47(2): 344-351.
[11]	KONG Wencong, HE Wubin, SU Rongjian, JIA Daqi, GU Yanjiao, WANG Yue, DU Xiaoyuan. Inhibitory effect and apoptosisinduction of MST1R inhibitor BMS-777607 on proliferation of breast cancer MCF-7 cells [J]. Journal of Jilin University(Medicine Edition), 2020, 46(03): 451-457.
[12]	CHEN Zhouhua, GONG Hui, FENG Lei, XIAO Yujie, HUANG Lizhong. Induction of LPS on epithelial mesenchymal transition in breast cancer MDA-MB-231 cells and its effect on β-catenin expression [J]. Journal of Jilin University(Medicine Edition), 2020, 46(02): 309-315.
[13]	ZHOU Chun, WANG Guanghua, ZHANG Bangzhu. Effects of miR-367 on proliferation, invasion and migration of human breast cancer MCF-7 cells and their mechanisms [J]. Journal of Jilin University(Medicine Edition), 2019, 45(06): 1353-1360.
[14]	YANG Zhuangqing, LU Mei, YANG Xiaojuan, WANG Chang'an, ZOU Jieya. Inhibitory effect of inhibiting TRIM24 gene expression on proliferation, apopotosis,invasion and migration of breast cancer MCF-7 cells [J]. Journal of Jilin University(Medicine Edition), 2019, 45(06): 1379-1383.
[15]	YUE Yuan, XU Yinglian, WANG Jingjing, SUN Minying, ZHANG Zenan, ZHAO Xinyue, LI Zongpu, TAI Guixiang. Inhibitory effects of down-regulation of JNK enzymatic activity on growth of human prostate cancer cells, hepatocellular carcinoma cells and breast cancer cells [J]. Journal of Jilin University(Medicine Edition), 2019, 45(05): 1046-1051.

Research progress in effect of intestinal flora on occurrence and development of breast cancer and its therapeutic application

RichHTML

PDF (PC)

Like

Knowledge

Abstract

Cite this article

share this article

References 52

Related Articles 15

Metrics

Comments

Recommended 10