Colorectal cancer (CRC) is one of the leading cancers in the world. With the influence of westernized lifestyle, the morbidity and mortality of CRC are on the rise in China. Gut microbiome comprises a large community of microorganisms in the intestinal tract, mainly bacteria and interacts with host to maintain human health. Change of many external and internal factors could reshape the structure of gut microbiome, which leads to the occurrence of CRC. More and more studies have shown that gut microbiome is closely related to the development of CRC. Among them, epidemiological sequencing data comprehensively revealed the characteristics of gut microbiome in CRC patients and potential of gut microbiome as a diagnostic marker for CRC, while animal experiments identified the carcinogenic mechanisms of various gut microbiome including Fusobacterium nucleatum. In this paper, we reviewed the relationship between gut microbiome and the occurrence and progress of CRC by combining the latest research results home and abroad, so as to provide ideas for further research on CRC and promote the clinical application of gut microbiome in prevention and treatment.

1. Goss PE, Strasser-Weippl K, Lee-Bychkovsky BL, et al. Challenges to effective cancer control in China, India, and Russia[J]. Lancet Oncol, 2014, 15(5): 489-538. DOI: 10.1016/S1470-2045(14)70029-4.

2. Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132. DOI: 10.3322/caac.21338.

3. Wong SH, Yu J. Gut microbiota in colorectal cancer: mechanisms of action and clinical applications[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(11): 690-704. DOI: 10.1038/s41575-019-0209-8.

4. Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies[J]. Nat Rev Gastroenterol Hepatol, 2019, 16(12): 713-732. DOI: 10.1038/s41575-019-0189-8.

5. Sommer F, Bäckhed F. The gut microbiota--masters of host development and physiology[J]. Nat Rev Microbiol, 2013, 11(4): 227-238. DOI: 10.1038/nrmicro2974.

6. Sender R, Fuchs S, Milo R. Revised Estimates for the Number of Human and Bacteria Cells in the Body[J]. PLoS Biol, 2016, 14(8): e1002533. DOI: 10.1371/journal.pbio.1002533.

7. Hollister EB, Riehle K, Luna RA, et al. Structure and function of the healthy pre-adolescent pediatric gut microbiome[J]. Microbiome, 2015, 3(1): 36. DOI: 10.1186/s40168-015-0101-x.

8. De Filippo C, Cavalieri D, Di Paola M, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa[J]. PNAS, 2010, 107(33): 14691-14696. DOI: 10.1073/pnas.1005963107.

9. So D, Whelan K, Rossi M, et al. Dietary fiber intervention on gut microbiota composition in healthy adults: a systematic review and meta-analysis[J]. Am J Clin Nutr, 2018, 107(6): 965-983. DOI: 10.1093/ajcn/nqy041.

10. David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome[J]. Nature, 2014, 505(7484): 559-563. DOI: 10.1038/nature12820.

11. Barton W, Penney NC. The microbiome of professional athletes differs from that of more sedentary subjects in composition and particularly at the functional metabolic level[J]. 2018, 67(4): 625-633. DOI: 10.1136/gutjnl-2016- 313627.

12. Palleja A, Mikkelsen KH, Forslund SK, et al. Recovery of gut microbiota of healthy adults following antibiotic exposure[J]. 2018, 3(11): 1255-1265. DOI: 10.1038/s41564 -018-0257-9.

13. Fassarella M, Blaak EE, Penders J, et al. Gut microbiome stability and resilience: elucidating the response to perturbations in order to modulate gut health[J/OL]. (2020-10-13)[Access on 2020-10-20]. https://gut.bmj.com/content/early/2020/10/13/gutjnl-2020-321747.

14. Nakatsu G, Li X, Zhou H, et al. Gut mucosal microbiome across stages of colorectal carcinogenesis[J]. Nat Commun, 2015, 6: 8727. DOI: 10.1038/ncomms9727.

15. Moore WE, Moore LH. Intestinal floras of populations that have a high risk of colon cancer[J]. Appl Environ Microbiol, 1995, 61(9): 3202-3207. DOI: 10.1128/AEM.61.9.3202-3207.1995.

16. Chen W, Liu F, Ling Z, et al. Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer[J]. PLoS One, 2012, 7(6): e39743. DOI: 10.1371/journal.pone.0039743.

17. Wang T, Cai G, Qiu Y, et al. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers[J]. Isme J, 2012, 6(2): 320-329. DOI: 10.1038/ismej.2011.109.

18. Wu N, Yang X, Zhang R, et al. Dysbiosis signature of fecal microbiota in colorectal cancer patients[J]. Microb Ecol, 2013, 66(2): 462-470. DOI: 10.1007/s00248-013-0245-9.

19. Zackular JP, Rogers MA, Ruffin MTt, et al. The human gut microbiome as a screening tool for colorectal cancer[J]. Cancer Prev Res (Phila), 2014, 7(11): 1112-1121. DOI: 10.1158/1940-6207.CAPR-14-0129.

20. Drewes JL, White JR, Dejea CM, et al. High-resolution bacterial 16S rRNA gene profile meta-analysis and biofilm status reveal common colorectal cancer consortia[J]. NPJ Biofilms Microbiomes, 2017, 3: 34. DOI: 10.1038/s41522-017-0040-3.

21. Feng Q, Liang S, Jia H, et al. Gut microbiome development along the colorectal adenoma-carcinoma sequence[J]. Nat Commun, 2015, 6: 6528. DOI: 10.1038/ncomms7528.

22. Yu J, Feng Q, Wong SH, et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer[J]. Gut, 2017, 66(1): 70-78. DOI: 10.1136/gutjnl-2015-309800.

23. Zeller G, Tap J, Voigt AY, et al. Potential of fecal microbiota for early-stage detection of colorectal cancer[J]. Mol Syst Biol, 2014, 10(11): 766. DOI: 10.15252/msb.20145645.

24. Wirbel J, Pyl PT, Kartal E, et al. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer[J]. Nat Med, 2019, 25(4): 679-689. DOI: 10.1038/s41591-019-0406-6.

25. Xie YH, Gao QY, Cai GX, et al. Fecal Clostridium symbiosum for Noninvasive Detection of Early and Advanced Colorectal Cancer: Test and Validation Studies[J]. EBioMedicine, 2017, 25: 32-40. DOI: 10.1016/j.ebiom. 2017.10.005.

26. Wong SH, Kwong TNY, Chow TC, et al. Quantitation of faecal Fusobacterium improves faecal immunochemical test in detecting advanced colorectal neoplasia[J]. Gut, 2017, 66(8): 1441-1448. DOI: 10.1136/gutjnl-2016-312766.

27. Yachida S, Mizutani S, Shiroma H, et al. Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer[J]. Nat Med, 2019, 25(6): 968-976. DOI: 10.1038/s41591-019-0458-7.

28. Nakatsu G, Zhou H, Wu WKK, et al. Alterations in Enteric Virome Are Associated With Colorectal Cancer and Survival Outcomes[J]. Gastroenterology, 2018, 155(2): 529-541. DOI: 10.1053/j.gastro.2018.04.018.

29. Thomas AM, Manghi P, Asnicar F, et al. Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation[J]. Nat Med, 2019, 25(4): 667-678. DOI: 10.1038/s41591-019-0405-7.

30. Coker OO, Nakatsu G, Dai RZ, et al. Enteric fungal microbiota dysbiosis and ecological alterations in colorectal cancer[J]. Gut, 2019, 68(4): 654-662. DOI: 10.1136/gutjnl-2018-317178.

31. Liang Q, Chiu J, Chen Y, et al. Fecal Bacteria Act as Novel Biomarkers for Noninvasive Diagnosis of Colorectal Cancer[J]. Clin Cancer Res, 2017, 23(8): 2061-2070. DOI: 10.1158/1078-0432.CCR-16-1599.

32. Eklöf V, Löfgren-Burström A, Zingmark C, et al. Cancer-associated fecal microbial markers in colorectal cancer detection[J]. Int J Cancer, 2017, 141(12): 2528-2536. DOI: 10.1002/ijc.31011.

33. Nougayrède JP, Homburg S, Taieb F, et al. Escherichia coli induces DNA double-strand breaks in eukaryotic cells[J]. Science, 2006, 313(5788): 848-851. DOI: 10.1126/science.1127059.

34. He Z, Gharaibeh RZ, Newsome RC, et al. Campylobacter jejuni promotes colorectal tumorigenesis through the action of cytolethal distending toxin[J]. Gut, 2019, 68(2): 289-300. DOI: 10.1136/gutjnl-2018-317200.

35. Wu S, Morin PJ, Maouyo D, et al. Bacteroides fragilis enterotoxin induces c-Myc expression and cellular proliferation[J]. Gastroenterology, 2003, 124(2): 392-400. DOI: 10.1053/gast.2003.50047.

36. Rubinstein MR, Wang X, Liu W, et al. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin[J]. Cell Host Microbe, 2013, 14(2): 195-206. DOI: 10.1016/j.chom.2013.07.012.

37. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer[J]. Cell, 2010, 140(6): 883-899. DOI: 10.1016/j.cell.2010.01.025.

38. Wong SH, Zhao L, Zhang X, et al. Gavage of Fecal Samples From Patients With Colorectal Cancer Promotes Intestinal Carcinogenesis in Germ-Free and Conventional Mice[J]. Gastroenterology, 2017, 153(6): 1621-1633.e1626. DOI: 10.1053/j.gastro.2017.08.022.

39. Chen J, Pitmon E, Wang K. Microbiome, inflammation and colorectal cancer[J]. Semin Immunol, 2017, 32: 43-53. DOI: 10.1016/j.smim.2017.09.006.

40. Arthur JC, Gharaibeh RZ, Mühlbauer M, et al. Microbial genomic analysis reveals the essential role of inflammation in bacteria-induced colorectal cancer[J]. Nat Commun, 2014, 5: 4724. DOI: 10.1038/ncomms5724.

41. Grivennikov SI, Wang K, Mucida D, et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth[J]. Nature, 2012, 491(7423): 254-258. DOI: 10.1038/nature11465.

42. Deng Z, Mu J, Tseng M, et al. Enterobacteria-secreted particles induce production of exosome-like S1P-containing particles by intestinal epithelium to drive Th17-mediated tumorigenesis[J]. Nat Commun, 2015, 6: 6956. DOI: 10.1038/ncomms7956.

43. Yang Y, Weng W, Peng J, et al. Fusobacterium nucleatum Increases Proliferation of Colorectal Cancer Cells and Tumor Development in Mice by Activating Toll-Like Receptor 4 Signaling to Nuclear Factor-κB, and Up-regulating Expression of MicroRNA-21[J]. Gastroenterology, 2017, 152(4): 851-866. DOI: 10.1053/j.gastro.2016.11.018.

44. Gur C, Ibrahim Y, Isaacson B, et al. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack[J]. Immunity, 2015, 42(2): 344-355. DOI: 10.1016/j.immuni. 2015.01.010.

45. Lu R, Wu S, Zhang YG, et al. Salmonella Protein AvrA Activates the STAT3 Signaling Pathway in Colon Cancer[J]. Neoplasia, 2016, 18(5): 307-316. DOI: 10.1016/j.neo.2016. 04.001.

46. Kim SW, Kim HM, Yang KM, et al. Bifidobacterium lactis inhibits NF-kappaB in intestinal epithelial cells and prevents acute colitis and colitis-associated colon cancer in mice[J]. Inflamm Bowel Dis, 2010, 16(9): 1514-1525. DOI: 10.1002/ibd.21262.

47. Chang PV, Hao L, Offermanns S, et al. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition[J]. Proc Natl Acad Sci USA, 2014, 111(6): 2247-2252. DOI: 10.1073/pnas.13222 69111.

48. de Aguiar Vallim TQ, Tarling EJ, Edwards PA. Pleiotropic roles of bile acids in metabolism[J]. Cell Metab, 2013, 17(5): 657-669. DOI: 10.1016/j.cmet.2013.03.013.

49. Saracut C, Molnar C, Russu C, et al. Secondary bile acids effects in colon pathology. Experimental mice study[J]. Acta Cir Bras, 2015, 30(9): 624-631. DOI: 10.1590/S0102-865020150090000007.

50. Bernstein H, Bernstein C, Payne CM, et al. Bile acids as endogenous etiologic agents in gastrointestinal cancer[J]. World J Gastroenterol, 2009, 15(27): 3329-3340. DOI: 10.3748/wjg.15.3329.

51. Li Y, Zhang X, Wang L, et al. Distribution and gene mutation of enteric flora carrying β-glucuronidase among patients with colorectal cancer[J]. Int J Clin Exp Med, 2015, 8(4): 5310-5316.

52. Goldin BR, Gorbach SL. Alterations of the intestinal microflora by diet, oral antibiotics, and Lactobacillus: decreased production of free amines from aromatic nitro compounds, azo dyes, and glucuronides[J]. J Natl Cancer Inst, 1984, 73(3): 689-695. DOI: 10.1093/jnci/73.3.689. 

53. Lin C, Cai X, Zhang J, et al. Role of Gut Microbiota in the Development and Treatment of Colorectal Cancer[J]. Digestion, 2019, 100(1): 72-78. DOI: 10.1159/000494052.

54. Alexander JL, Wilson ID, Teare J, et al. Gut microbiota modulation of chemotherapy efficacy and toxicity[J]. Nat Rev Gastroenterol Hepatol, 2017, 14(6): 356-365. DOI: 10.1038/nrgastro.2017.20.

55. Gopalakrishnan V, Helmink BA, Spencer CN, et al. The Influence of the Gut Microbiome on Cancer, Immunity, and Cancer Immunotherapy[J]. Cancer Cell, 2018, 33(4): 570-580. DOI: 10.1016/j.ccell.2018.03.015.

56. 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. DOI: 10.1016/j.cell.2017.07.008.

57. Yeung CY, Chan WT, Jiang CB, et al. Amelioration of Chemotherapy-Induced Intestinal Mucositis by Orally Administered Probiotics in a Mouse Model[J]. PLoS One, 2015, 10(9): e0138746. DOI: 10.1371/journal.pone.0138 746.

58. Mego M, Chovanec J, Vochyanova-Andrezalova I, et al. Prevention of irinotecan induced diarrhea by probiotics: A randomized double blind, placebo controlled pilot study[J]. Complement Ther Med, 2015, 23(3): 356-362. DOI: 10.1016/j.ctim.2015.03.008.

59. Yan X, Sivignon A, Yamakawa N, et al. Glycopolymers as Antiadhesives of E. coli Strains Inducing Inflammatory Bowel Diseases[J]. Biomacromolecules, 2015, 16(6): 1827-1836. DOI: 10.1021/acs.biomac.5b00413.

60. Chen ZF, Ai LY, Wang JL, et al. Probiotics Clostridium butyricum and Bacillus subtilis ameliorate intestinal tumorigenesis[J]. Future Microbiol, 2015, 10(9): 1433-1445. DOI: 10.2217/fmb.15.66.