Research progress on intestinal flora and non-surgical treatment of the colorectal cancer

Abstract

Abstract:

In recent years， intestinal flora has gradually become the focus of research on the treatment of malignant neoplasms. Intestinal opportunistic pathogens （such asFusobacterium nucleatum，Bacteroides fragilis）， intestinal probiotics （such asClostridium butyricum，Lactic acid bacteria） and intestinal pathogenic bacteria （such asSalmonella，Shigella） can affect the efficacy and related adverse reactions of radiotherapy， chemotherapy and immunotherapy for the colorectal cancer （CRC） by influencing signaling pathways， modulating autophagy， regulating immune response， producing metabolites and toxins， and transplanting fecal bacteria. At the same time， it provides a large number of potential targets for targeted therapy of the CRC. Further research on the relationship between intestinal flora and non-surgical treatment of the CRC can provide references for basic and clinical research of non-surgical treatment of the CRC.

Key words:Colorectal neoplasms,Gastrointestinal microbiome,Drug therapy,Radiotherapy,Immunotherapy

Gao Fan, Wang Ping, Du Chao, Chu Yanliu. Research progress on intestinal flora and non-surgical treatment of the colorectal cancer[J]. Journal of International Oncology, 2024, 51(6): 376-381.

References62

[1]	周雄, 胡明, 李子帅, 等. 2020年全球及中国结直肠癌流行状况分析[J].海军军医大学学报,2022,43(12): 1356-1364. DOI:10.16781/j.CN31-2187/R.20220593.
[2]	陈海宁, 王自强, 于永扬, 等. 从全球趋势看我国结直肠癌防控:挑战与策略[J].中国科学(生命科学),2022,52(11): 1612-1625.
[3]	宋德心, 王伟东, 高瑞祺, 等. 肠道菌群在结直肠癌发生发展和诊断治疗中的作用研究进展[J].中国普通外科杂志,2022,31(4): 527-536. DOI:10.7659/j.issn.1005-6947.2022.04.015.
[4]	Jiang SS, Xie YL, Xiao XY, et al. Fusobacterium nucleatum-derived succinic acid induces tumor resistance to immunotherapy in colorectal cancer[J].Cell Host Microbe,2023,31(5): 781-797.e9. DOI:10.1016/j.chom.2023.04.010.
[5]	Wang ZK, Dan WY, Zhang NN, et al. Colorectal cancer and gut microbiota studies in China[J].Gut Microbes,2023,15(1): 2236364. DOI:10.1080/19490976.2023.2236364.
[6]	Gao YH, Bi DX, Xie RT, et al. Fusobacterium nucleatum enhances the efficacy of PD-L1 blockade in colorectal cancer[J].Signal Transduct Target Ther,2021,6(1): 398. DOI:10.1038/s41392-021-00795-x.
[7]	Yu TC, Guo FF, Yu YN, et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy[J].Cell,2017,170(3): 548-563.e16. DOI:10.1016/j.cell.2017.07.008. pmid:28753429
[8]	Zhang S, Yang YZ, Weng WH, et al. Fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of BIRC3 expression in colorectal cancer[J].J Exp Clin Cancer Res,2019,38(1): 14. DOI:10.1186/s13046-018-0985-y. pmid:30630498
[9]	Dong JL, Li Y, Xiao HW, et al. Oral microbiota affects the efficacy and prognosis of radiotherapy for colorectal cancer in mouse models[J].Cell Rep,2021,37(4): 109886. DOI:10.1016/j.celrep.2021.109886.
[10]	吕志堂, 许晓娜, 张怡君. 脆弱拟杆菌在炎症性肠病、结直肠癌促进、调控及防治中的作用[J].微生物学杂志,2020,40(4): 1-8. DOI:10.3969/j.issn.1005-7021.2020.04.001.
[11]	Boleij A, Hechenbleikner EM, Goodwin AC, et al. The bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients[J].Clin Infect Dis,2015,60(2): 208-215. DOI:10.1093/cid/ciu787. pmid:25305284
[12]	Wu SG, Dreyfus LA, Tzianabos AO, et al. Diversity of the metalloprotease toxin produced by enterotoxigenic bacteroides fragilis[J].Infect Immun,2002,70(5): 2463-2471. DOI:10.1128/iai.70.5.2463-2471.2002. pmid:11953383
[13]	Xie XL, Jiang D, Zhou XB, et al. Recombinant bacteroides fragilis enterotoxin-1 (rBFT-1) promotes proliferation of colorectal cancer via CCL3-related molecular pathways[J].Open Life Sci,2021,16(1): 408-418. DOI:10.1515/biol-2021-0043.
[14]	Lv Y, Ye T, Wang HP, et al. Suppression of colorectal tumorige-nesis by recombinant bacteroides fragilis enterotoxin-2 in vivo[J].World J Gastroenterol,2017,23(4): 603-613. DOI:10.3748/wjg.v23.i4.603.
[15]	Sittipo P, Lobionda S, Choi K, et al. Toll-Like receptor 2-mediated suppression of colorectal cancer pathogenesis by polysaccharide a from bacteroides fragilis[J].Front Microbiol,2018,9: 1588. DOI:10.3389/fmicb.2018.01588. pmid:30065713
[16]	Lee YK, Mehrabian P, Boyajian SL, et al. The protective role of bacteroides fragilis in a murine model of colitis-associated colorectal cancer[J].mSphere,2018,3(6): e00587-18. DOI:10.1128/mSphere.00587-18.
[17]	Pandey H, Tang DWT, Wong SH, et al. Gut microbiota in colorectal cancer: biological role and therapeutic opportunities[J].Cancers (Basel),2023,15(3): 866. DOI:10.3390/cancers15030866.
[18]	Spanogiannopoulos P, Kyaw TS, Guthrie BGH, et al. Host and gut bacteria share metabolic pathways for anti-cancer drug metabolism[J].Nat Microbiol,2022,7(10): 1605-1620. DOI:10.1038/s41564-022-01226-5. pmid:36138165
[19]	Lopès A, Billard E, Casse AH, et al. Colibactin-positive escherichia coli induce a procarcinogenic immune environment leading to immunotherapy resistance in colorectal cancer[J].Int J Cancer,2020,146(11): 3147-3159. DOI:10.1002/ijc.32920. pmid:32037530
[20]	Gagnière J, Bonnin V, Jarrousse AS, et al. Interactions between microsatellite instability and human gut colonization by escherichia coli in colorectal cancer[J].Clin Sci (Lond),2017,131(6): 471-485. DOI:10.1042/cs20160876. pmid:28093453
[21]	Alizadeh S, Esmaeili A, Omidi Y. Anti-cancer properties of escherichia coli nissle 1917 against HT-29 colon cancer cells through regulation of Bax/Bcl-xL and AKT/PTEN signaling pathways[J].Iran J Basic Med Sci,2020,23(7): 886-893. DOI:10.22038/ijbms.2020.43016.10115. pmid:32774810
[22]	Chiang CJ, Hong YH. In situ delivery of biobutyrate by probiotic escherichia coli for cancer therapy[J].Sci Rep,2021,11(1): 18172. DOI:10.1038/s41598-021-97457-3.
[23]	Yu XL, Lin CS, Yu J, et al. Bioengineered escherichia coli nissle 1917 for tumour-targeting therapy[J].Microb Biotechnol,2020,13(3): 629-636. DOI:10.1111/1751-7915.13523. pmid:31863567
[24]	Nougayrède JP, Chagneau CV, Motta JP, et al. A toxic friend: genotoxic and mutagenic activity of the probiotic strain escherichia coli nissle 1917[J].mSphere,2021,6(4): e0062421. DOI:10.1128/mSphere.00624-21.
[25]	Kaiser P. Methionine dependence of cancer[J].Biomolecules,2020,10(4): 568. DOI:10.3390/biom10040568.
[26]	Kubota Y, Han QH, Hamada K, et al. Oral installation of recombinant methioninase-producing escherichia coli into the microbiome inhibits colon-cancer growth in a syngeneic mouse model[J].Cancer Genomics Proteomics,2022,19(6): 683-691. DOI:10. 21873/cgp.20351.
[27]	Zhou M, Yuan W, Yang B, et al. Clostridium butyricum inhibits the progression of colorectal cancer and alleviates intestinal inflammation via the myeloid differentiation factor 88(MyD88)-nuclear factor-kappa B(NF-κB)signaling pathway[J].Ann Transl Med,2022,10(8): 478. DOI:10.21037/atm-22-1670.
[28]	He Y, Fu LH, Li YP, et al. Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8⁺T cell immunity[J].Cell Metab,2021,33(5): 988-1000.e7. DOI:10.1016/j.cmet.2021.03.002.
[29]	Nomura M, Nagatomo R, Doi K, et al. Association of short-chain fatty acids in the gut microbiome with clinical response to treatment with nivolumab or pembrolizumab in patients with solid cancer tumors[J].JAMA Netw Open, 2020, 3(4): e202895. DOI:10.1001/jamanetworkopen.2020.2895.
[30]	Chen JZ, Zhao KN, Vitetta L. Effects of intestinal microbial- elaborated butyrate on oncogenic signaling pathways[J].Nutrients,2019,11(5): 1026. DOI:10.3390/nu11051026.
[31]	Stoeva MK, Garcia-So J, Justice N, et al. Butyrate-producing human gut symbiont, clostridium butyricum, and its role in health and disease[J].Gut Microbes,2021,13(1): 1-28. DOI:10.1080/19490976.2021.1907272.
[32]	Pu W, Zhang H, Zhang T, et al. Inhibitory effects of clostridium butyricum culture and supernatant on inflammatory colorectal cancer in mice[J].Front Immunol,2023: 1004756. DOI:10.3389/fimmu.2023.1004756.
[33]	Chen DF, Jin DC, Huang SM, et al. Clostridium butyricum, a butyrate-producing probiotic, inhibits intestinal tumor development through modulating wnt signaling and gut microbiota[J].Cancer Lett,2020,469: 456-467. DOI:10.1016/j.canlet.2019.11.019. pmid:31734354
[34]	Hradicka P, Beal J, Kassayova M, et al. A novel lactic acid bacteria mixture: macrophage-targeted prophylactic intervention in colorectal cancer management[J].Microorganisms,2020,8(3): 387. DOI:10.3390/microorganisms8030387.
[35]	An JJ, Ha EM. Combination therapy of lactobacillus plantarum supernatant and 5-fluouracil increases chemosensitivity in colorectal cancer cells[J].J Microbiol Biotechnol,2016,26(8): 1490-1503. DOI:10.4014/jmb.1605.05024.
[36]	An JJ, Ha EM. Lactobacillus-derived metabolites enhance the antitumor activity of 5-FU and inhibit metastatic behavior in 5-FU-resistant colorectal cancer cells by regulating claudin-1 expression[J].J Microbiol,2020,58(11): 967-977. DOI:10.1007/s12275-020-0375-y. pmid:33125671
[37]	An JJ, Ha EM. Extracellular vesicles derived from lactobacillus plantarum restore chemosensitivity through the PDK2-mediated glucose metabolic pathway in 5-FU-resistant colorectal cancer cells[J].J Microbiol,2022,60(7): 735-745. DOI:10.1007/s12275-022-2201-1. pmid:35781627
[38]	An JJ, Seok H, Ha EM. GABA-producing lactobacillus plantarum inhibits metastatic properties and induces apoptosis of 5-FU-resistant colorectal cancer cells via GABAB receptor signaling[J].J Microbiol,2021,59(2): 202-216. DOI:10.1007/s12275-021-0562-5.
[39]	Kim HJ, An JJ, Ha EM. Lactobacillus plantarum-derived metabolites sensitize the tumor-suppressive effects of butyrate by regula-ting the functional expression of SMCT1 in 5-FU-resistant colorectal cancer cells[J].J Microbiol,2022,60(1): 100-117. DOI:10.1007/s12275-022-1533-1.
[40]	Zhang QQ, Zhao Q, Li T, et al. Lactobacillus plantarum-derived indole-3-lactic acid ameliorates colorectal tumorigenesis via epigenetic regulation of CD8⁺T cell immunity[J].Cell Metab,2023,35(6): 943-960.e9. DOI:10.1016/j.cmet.2023.04.015.
[41]	Amin M, Navidifar T, Saeb S, et al. Tumor-targeted induction of intrinsic apoptosis in colon cancer cells by lactobacillus plantarum and lactobacillus rhamnosus strains[J].Mol Biol Rep,2023,50(6): 5345-5354. DOI:10.1007/s11033-023-08445-x. pmid:37155013
[42]	Si W, Liang H, Bugno J, et al. Lactobacillus rhamnosus GG induces cGAS/STING- dependent type Ⅰ interferon and improves response to immune checkpoint blockade[J].Gut,2022,71(3): 521-533. DOI:10.1136/gutjnl-2020-323426.
[43]	Owens JA, Saeedi BJ, Naudin CR, et al. Lactobacillus rhamnosus GG orchestrates an antitumor immune response[J].Cell Mol Gastroenterol Hepatol,2021,12(4): 1311-1327. DOI:10.1016/j.jcmgh.2021.06.001.
[44]	Osterlund P, Ruotsalainen T, Korpela R, et al. Lactobacillus supplementation for diarrhoea related to chemotherapy of colorectal cancer: a randomised study[J].Br J Cancer,2007,97(8): 1028-1034. DOI:10.1038/sj.bjc.6603990.
[45]	Dougherty MW, Jobin C. Intestinal bacteria and colorectal cancer: etiology and treatment[J].Gut Microbes,2023,15(1): 2185028. DOI:10.1080/19490976.2023.2185028.
[46]	Li Q, Hu W, Liu WX, et al. Streptococcus thermophilus inhibits colorectal tumorigenesis through secreting β-galactosidase[J].Gastroenterology,2021,160(4): 1179-1193.e14. DOI:10.1053/j.gastro.2020.09.003. pmid:32920015
[47]	Yenuganti VR, Yadala R, Azad R, et al. In vitro evaluation of anticancer effects of different probiotic strains on HCT-116 cell line[J].J Appl Microbiol,2021,131(4): 1958-1969. DOI:10.1111/jam.15060. pmid:33694215
[48]	Wang YH, Yao N, Wei KK, et al. The efficacy and safety of probiotics for prevention of chemoradiotherapy-induced diarrhea in people with abdominal and pelvic cancer: a systematic review and meta-analysis[J].Eur J Clin Nutr,2016,70(11): 1246-1253. DOI:10.1038/ejcn.2016.102. pmid:27329608
[49]	Liu MM, Li ST, Shu Y, et al. Probiotics for prevention of radiation-induced diarrhea: a meta-analysis of randomized controlled trials[J].PLoS One,2017,12(6): e0178870. DOI:10.1371/journal.pone.0178870.
[50]	Guo YX, Chen Y, Liu XQ, et al. Targeted cancer immunotherapy with genetically engineered oncolytic salmonella typhimurium[J].Cancer Lett,2020,469: 102-110. DOI:10.1016/j.canlet.2019.10.033. pmid:31666180
[51]	Lee CH. Employment of salmonella in cancer gene therapy[J].Methods Mol Biol,2016,1409: 79-83. DOI:10.1007/978-1-4939-3515-4_8.
[52]	Liu L, Zhang J, Gu M, et al. Antitumor effect of cycle inhibiting factor expression in colon cancer via salmonella VNP20009[J].Anticancer Agents Med Chem,2020,20(14): 1722-1727. DOI:10.2174/1871520620666200423080622.
[53]	Liu ZC, Li X, Lu ZK, et al. Repurposing the pentameric B-subunit of shiga toxin for Gb3-targeted immunotherapy of colorectal cancer by rhamnose conjugation[J].J Pharm Sci,2022,111(10): 2719-2729. DOI:10.1016/j.xphs.2022.07.017.
[54]	Aguiar SLF, Miranda MCG, Guimarães MAF, et al. High-salt diet induces IL-17-dependent gut inflammation and exacerbates colitis in mice[J].Front Immunol,2018,8: 1969. DOI:10.3389/fimmu.2017.01969.
[55]	Housseau F, Wu SG, Wick EC, et al. Redundant innate and adaptive sources of IL17 production drive colon tumorigenesis[J].Cancer Res,2016,76(8): 2115-2124. DOI:10.1158/0008-5472.Can-15-0749. pmid:26880802
[56]	Hwang S, Yi HC, Hwang S, et al. Dietary salt administration decreases enterotoxigenic bacteroides fragilis (ETBF)-promoted tumorigenesis via inhibition of colonic inflammation[J].Int J Mol Sci,2020,21(21): 8034. DOI:10.3390/ijms21218034.
[57]	Li S, Liu JY, Zheng XJ, et al. Tumorigenic bacteria in colorectal cancer: mechanisms and treatments[J].Cancer Biol Med,2021,19(2): 147-162. DOI:10.20892/j.issn.2095-3941.2020.0651.
[58]	Blaser MJ. Antibiotic use and its consequences for the normal microbiome[J].Science,2016,352(6285): 544-545. DOI:10.1126/science.aad9358. pmid:27126037
[59]	Boursi B, Haynes K, Mamtani R, et al. Impact of antibiotic exposure on the risk of colorectal cancer[J].Pharmacoepidemiol Drug Saf,2015,24(5): 534-542. DOI:10.1002/pds.3765. pmid:25808540
[60]	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. DOI:10.1126/science.aan3706. pmid:29097494
[61]	Huang JY, Zheng X, Kang WY, et al. Metagenomic and metabolomic analyses reveal synergistic effects of fecal microbiota transplantation and anti-PD-1 therapy on treating colorectal cancer[J].Front Immunol,2022,13: 874922. DOI:10.3389/fimmu.2022.874922.
[62]	DeFilipp Z, Bloom PP, Torres Soto M, et al. Drug-resistant E. coli Bacteremia transmitted by fecal microbiota transplant[J].N Engl J Med,2019,381(21): 2043-2050. DOI:10.1056/NEJMoa1910437.