Роль кишечной микробиоты в колоректальном канцерогенезе (обзор литературы)

Цель обзора литературы – показать возможные связи между кишечной микробиотой и канцерогенезом колоректального рака, описать проканцерогенные свойства микроорганизмов, связанных с возникновением или пролиферацией рака. Кишечная микробиота играет ведущую роль в метаболизме, предоставляя важные метаболиты макроорганизму. В организме человека существует пространственная изменчивость в качественном и количественном составе микробиоты. Кишечная микробиота обеспечивает колониерезистентность организма человека, защищая его от колонизации условнопатогенными и патогенными микроорганизмами. Все больше появляется данных о роли кишечной микробиоты в возникновении и развитии колоректального рака. Требуется углубленное исследования кишечного микробиома в различных популяциях, что позволит идентифицировать другие микроорганизмы, связанные с возникновением или пролиферацией КРР, которые в дальнейшем могут быть использованы в качестве биомаркеров для скрининга КРР и прогнозирования ответа на иммунотерапию.

1. Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet. 2014;383:1490-1502. DOI: 10.1016/S0140-6736(13)61649-9

2. Qin J, Li R, Raes J, Arumugam M. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59-65. DOI: 10.1038/nature08821

3. Gao Z, Guo B, Gao R. et al. Microbiota disbiosis is associated with colorectal cancer. Front Microbiol. 2015. DOI: 10.3389/fmicb.2015.00020

4. Van der Beek CM, Dejong CHC, Troost FJ. et al. Role of short-chain fatty acids in colonic inflammation, carcinogenesis, and mucosal protection and healing. Nutr Rev. 2017;75:286-305. DOI: 10.1093/nutrit/nuw067

5. Kurzawski G, Suchy J, Kładny J. et al. The NOD2 3020insC mutation and the risk of colorectal cancer. Cancer Res. 2004;64:1604-1606. DOI: 10.1158/0008-5472.CAN-03-3791

6. Zhan Y, Seregin SS, Chen J. et al. Nod1 Limits Colitis-Associated Tumorigenesis by Regulating IFN-γ Production. J Immunol. 2016;196:5121-5129. DOI: 10.4049/jimmunol.1501822

7. Plummer M, de Martel C, Vignat J. et al. Global burden of cancers attributable to infections in 2012: A synthetic analysis. Lancet Glob Health. 2016;4:609-e616. DOI: 10.1016/S2214-109X(16)30143-7

8. Moore WE, Moore LH. Intestinal floras of populations that have a high risk of colon cancer. Appl Environ Microbiol. 1995;61:3202-3207

9. McCoy AN, Araújo-Pérez F, Azcárate-Peril A. et al. Fusobacterium Is Associated with Colorectal Adenomas. PLoS ONE. 2013. DOI: 10.1371/journal.pone.0053653

10. Wang T, Cai G, Qiu Y. et al. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J. 2012;6:320-329. DOI: 10.1038/ismej.2011.109

11. Viljoen KS, Dakshinamurthy A, Goldberg P. et al. Quantitative profiling of colorectal cancer-associated bacteria reveals associations between fusobacterium spp., enterotoxigenic Bacteroides fragilis (ETBF) and clinicopathological features of colorectal cancer. PLoS ONE. 2015. DOI: 10.1371/journal.pone.0119462

12. Zhu Q, Jin Z, Wu W. et al. Analysis of the Intestinal Lumen Microbiota in an Animal Model of Colorectal Cancer. PLoS ONE. 2014. DOI: 10.1371/journal.pone.0090849

13. Tjalsma H, Boleij A, Marchesi JR. et al. A bacterial driver–passenger model for colorectal cancer: Beyond the usual suspects. Nat Rev Microbiol. 2012;10:575-582. DOI: 10.1038/nrmicro2819

14. Amarnani R, Rapose A. Colon cancer and enterococcus bacteremia co-affection: A dangerous alliance. J Infect Public Health. 2017. DOI: 10.1016/j.jiph.2016.09.009

15. Ruiz PA, Shkoda A, Kim SC. et al. IL-10 gene-deficient mice lack TGF-beta/Smad signaling and fail to inhibit proinflammatory gene expression in intestinal epithelial cells after the colonization with colitogenic Enterococcus faecalis. J Immunol. 2005;174:2990-2999. DOI: 10.4049/jimmunol.174.5.2990

16. Wang X, Huycke MM. Extracellular superoxide production by Enterococcus faecalis promotes chromosomal instability in mammalian cells. Gastroenterology. 2007;132:551-561. DOI: 10.1053/j.gastro.2006.11.040

17. Zhang G, Svenungsson B, Kärnell A. et al. Prevalence of enterotoxigenic Bacteroides fragilis in adult patients with diarrhea and healthy controls. Clin Infect Dis. 1999;29:590-594. DOI: 10.1086/598639

18. Toprak NU, Yagci A, Gulluoglu BM. et al. A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer. Clin Microbiol Infect. 2006;12:782-786. DOI: 10.1111/j.1469-0691.2006.01494.x

19. Purcell RV, Pearson J, Aitchison A. et al. Colonization with enterotoxigenic Bacteroides fragilis is associated with earlystage colorectal neoplasia. PLoS ONE. 2017. DOI: 10.1371/journal.pone.0171602

20. Wu S, Morin PJ, Maouyo D. et al. Bacteroides fragilis enterotoxin induces c-myc expression and cellular proliferation. Gastroenterology. 2003;2:392-400. DOI: 10.1053/gast.2003.50047

21. Han YW. Fusobacterium nucleatum: A commensal-turned pathogen. Curr Opin Microbiol. 2015;23:141-147. DOI: 10.1016/j.mib.2014.11.013

22. 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. Gastroenterology. 2017;152:851-866. DOI: 10.1053/j.gastro.2016.11.018

23. Kostic AD, Chun E, Robertson L. et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor immune microenvironment. Cell Host Microbe. 2013;14:207-215. DOI: 10.1016/j.chom.2013.07.007

24. Klein RS, Recco RA, Catalano MT. et al Association of Streptococcus bovis with carcinoma of the colon. N Engl J Med. 1977;297:800-802. DOI: 10.1056/NEJM197710132971503

25. Ellmerich S, Schöller M, Duranton B. et al. Promotion of intestinal carcinogenesis by Streptococcus bovis. Carcinogenesis. 2000;21:753- 756. DOI: 10.1093/carcin/21.4.753

26. Ballard J, Bryant A, Stevens D. et al. Purification and characterization of the lethal toxin (alpha-toxin) of Clostridium septicum. Infect Immun. 1992;60:784-790

27. Mirza NN, McCloud JM, Cheetham MJ. Clostridium septicum sepsis and colorectal cancer – A reminder. World J Surg Oncol. 2009;7:73. DOI: 10.1186/1477-7819-7-73

28. Hong SN, Lee SM, Kim JH. et al. Helicobacter pylori infection increases the risk of colorectal adenomas: Cross-sectional study and meta-analysis. Dig Dis Sci. 2012;57:2184-2194. DOI: 10.1007/s10620-012-2245-x

29. Yan Y, Chen Y-N, Zhao Q. et al. Helicobacter pylori infection with intestinal metaplasia: An independent risk factor for colorectal adenomas. World J Gastroenterol. 2017;23:1443-1449. DOI: 10.3748/wjg.v23.i8.1443

30. Hartwich A, Konturek S, Pierzchalski P. et al. Helicobacter pylori infection, gastrin, cyclooxygenase-2, and apoptosis in colorectal cancer. Int J Colorectal Dis. 2001;16:202-210. DOI: 10.1007/s003840100288

31. Handa O, Naito Y, Yoshikawa T. Helicobacter pylori: A ROSinducing bacterial species in the stomach. Inflamm Res. 2010;59:997- 1003. DOI: 10.1007/s00011-010-0245-x

32. Shmuely H, Passaro D, Figer A. et al. Relationship between Helicobacter pylori CagA status and colorectal cancer. Am J Gastroenterol. 2001;96:3406-3410. DOI: 10.1111/j.1572-0241.2001.05342.x

33. Wessler S, Krisch LM, Elmer DP. et al. From inflammation to gastric cancer – The importance of Hedgehog/GLI signaling in Helicobacte r pylori-induced chronic inflammatory and neoplastic diseases. Cell Commun Signal. 2017. DOI: 10.1186/s12964-017-0171-4

34. Sousa CP. The versatile strategies of Escherichia coli pathotypes: A mini review. J Venom Anim Toxins Trop Dis. 2006;12:363-373. DOI: 10.1590/S1678-91992006000300002

35. Maddocks ODK., Short AJ, Donnenberg MS. et al. Attaching and effacing Escherichia coli downregulate DNA mismatch repair protein in vitro and are associated with colorectal adenocarcinomas in humans. PLoS ONE. 2009. DOI: 10.1371/journal.pone.0005517

36. Bonnet M, Buc E, Sauvanet P. et al. Colonization of the human gut by E. coli and colorectal cancer risk. Clin Cancer Res. 2014;20:859- 867. DOI: 10.1158/1078-0432.CCR-13-1343

37. Marchès O, Ledger TN, Boury M. et al. Enteropathogenic and enterohaemorrhagic Escherichia coli deliver a novel effector called Cif, which blocks cell cycle G2/M transition. Mol Microbiol. 2003;50:1553-1567. DOI: 10.1046/j.1365-2958.2003.03821.x

38. Flatau G, Lemichez E, Gauthier M. et al. Toxin-induced activation of the G protein p21 Rho by deamidation of glutamine. Nature. 1997;387:729-733

39. Nougayrède J-P, Homburg S, Taieb F. et al. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science. 2006;313:848-851. DOI: 10.1126/science.1127059

40. Vizcaino MI, Crawford JM. The colibactin warhead crosslinks DNA. Nat Chem. 2015;7:411-417. DOI: 10.1038/nchem.2221