Altered intestinal microbiota associated with colorectal cancer

  • Hong Zhang
  • Ying Chang
  • Qingqing Zheng
  • Rong Zhang
  • Cheng HuEmail author
  • Weiping Jia
Research Article


The gut microbiota plays an important role in the development and progression of colorectal cancer (CRC). To learn more about the dysbiosis of carcinogenesis, we assessed alterations in gut microbiota in patients with CRC. A total of 23 subjects were enrolled in this study: 9 had CRC (CRC group) and 14 had normal colons (normal group). The microbiome of the mucosal—luminal interface of each subject was sampled and analyzed using 16S rRNA gene amplicon sequencing. We also used Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to predict microbial functional profiles. The microbial composition of the mucosal lumen differed between the groups, and the presence of specific bacteria may serve as a potential biomarker for colorectal carcinogenesis. We identified a significant reduction in Eubacterium, which is a butyrate-producing genera of bacteria, and a significant increase in Devosia in the gut microbiota of CRC patients. Different levels of gut microflora in healthy and CRC samples were identified. The observed abundance of bacterial species belonging to Eubacterium and Devosia may serve as a promising biomarker for the early detection of CRC.


colorectal cancer (CRC) gut microbiota intestinal Eubacterium Devosia 


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This current study was supported by the Shanghai Sixth People’s Hospital Grant (No. YNLC201725), the National Natural Science Foundation of China (No. 81800708), Outstanding Academic Leaders of Shanghai Health System (No. 2017BR008) and Yangtze River Scholar.

Supplementary material

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  1. 1.
    Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, Starling N. Colorectal cancer. Lancet 2010; 375(9719): 1030–1047CrossRefGoogle Scholar
  2. 2.
    Regula J, Rupinski M, Kraszewska E, Polkowski M, Pachlewski J, Orlowska J, Nowacki MP, Butruk E. Colonoscopy in colorectal-cancer screening for detection of advanced neoplasia. N Engl J Med 2006; 355(18): 1863–1872CrossRefGoogle Scholar
  3. 3.
    Azcárate-Peril MA, Sikes M, Bruno-Bárcena JM. The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer? Am J Physiol Gastrointest Liver Physiol 2011; 301(3): G401–G424CrossRefGoogle Scholar
  4. 4.
    Horiuchi Y, Fujisaki J, Ishizuka N, Omae M, Ishiyama A, Yoshio T, Hirasawa T, Yamamoto Y, Nagahama M, Takahashi H, Tsuchida T. Study on clinical factors involved in Helicobacter pylori-uninfected, undifferentiated-type early gastric cancer. Digestion 2017; 96(4): 213–219CrossRefGoogle Scholar
  5. 5.
    Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S. Host-gut microbiota metabolic interactions. Science 2012; 336(6086): 1262–1267CrossRefGoogle Scholar
  6. 6.
    Yatsunenko T, Rey FE, Manary MJ, Trehan I, Dominguez-Bello MG, Contreras M, Magris M, Hidalgo G, Baldassano RN, Anokhin AP, Heath AC, Warner B, Reeder J, Kuczynski J, Caporaso JG, Lozupone CA, Lauber C, Clemente JC, Knights D, Knight R, Gordon JI. Human gut microbiome viewed across age and geography. Nature 2012; 486(7402): 222–227CrossRefGoogle Scholar
  7. 7.
    Parkin DM. The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006; 118(12): 3030–3044CrossRefGoogle Scholar
  8. 8.
    Amitay EL, Werner S, Vital M, Pieper DH, Höfler D, Gierse IJ, Butt J, Balavarca Y, Cuk K, Brenner H. Fusobacterium and colorectal cancer: causal factor or passenger? Results from a large colorectal cancer screening study. Carcinogenesis 2017; 38(8): 781–788CrossRefGoogle Scholar
  9. 9.
    Yamaoka Y, Suehiro Y, Hashimoto S, Hoshida T, Fujimoto M, Watanabe M, Imanaga D, Sakai K, Matsumoto T, Nishioka M, Takami T, Suzuki N, Hazama S, Nagano H, Sakaida I, Yamasaki T. Fusobacterium nucleatum as a prognostic marker of colorectal cancer in a Japanese population. J Gastroenterol 2018; 53(4): 517–524CrossRefGoogle Scholar
  10. 10.
    Repass J, Maherali N, Owen K, Reproducibility Project: Cancer Biology. Registered report: Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. eLife 2016; 5:e10012CrossRefGoogle Scholar
  11. 11.
    Mira-Pascual L, Cabrera-Rubio R, Ocon S, Costales P, Parra A, Suarez A, Moris F, Rodrigo L, Mira A, Collado MC. Microbial mucosal colonic shifts associated with the development of colorectal cancer reveal the presence of different bacterial and archaeal biomarkers. J Gastroenterol 2015; 50(2): 167–179CrossRefGoogle Scholar
  12. 12.
    Mottawea W, Chiang CK, Mühlbauer M, Starr AE, Butcher J, Abujamel T, Deeke SA, Brandel A, Zhou H, Shokralla S, Hajibabaei M, Singleton R, Benchimol EI, Jobin C, Mack DR, Figeys D, Stintzi A. Altered intestinal microbiota-host mitochondria crosstalk in new onset Crohn’s disease. Nat Commun 2016; 7(1): 13419CrossRefGoogle Scholar
  13. 13.
    Quast C, Pruesse E, Yilmaz P, Gerken J, Schweer T, Yarza P, Peplies J, Glöckner FO. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res 2013; 41(Database issue): D590–D596CrossRefGoogle Scholar
  14. 14.
    Schloss PD, Westcott SL, Ryabin T, Hall JR, Hartmann M, Hollister EB, Lesniewski RA, Oakley BB, Parks DH, Robinson CJ, Sahl JW, Stres B, Thallinger GG, Van Horn DJ, Weber CF. Introducing mothur: open-source, platform-independent, community-supported software for describing and comparing microbial communities. Appl Environ Microbiol 2009; 75(23): 7537–7541CrossRefGoogle Scholar
  15. 15.
    Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, Huttenhower C. Metagenomic biomarker discovery and explanation. Genome Biol 2011; 12(6): R60CrossRefGoogle Scholar
  16. 16.
    Langille MG, Zaneveld J, Caporaso JG, McDonald D, Knights D, Reyes JA, Clemente JC, Burkepile DE, Vega Thurber RL, Knight R, Beiko RG, Huttenhower C. Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol 2013; 31(9): 814–821CrossRefGoogle Scholar
  17. 17.
    Ley RE, Peterson DA, Gordon JI. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 2006; 124(4): 837–848CrossRefGoogle Scholar
  18. 18.
    Kimura K, McCartney AL, McConnell MA, Tannock GW. Analysis of fecal populations of bifidobacteria and lactobacilli and investigation of the immunological responses of their human hosts to the predominant strains. Appl Environ Microbiol 1997; 63(9): 3394–3398Google Scholar
  19. 19.
    Sears CL. A dynamic partnership: celebrating our gut flora. Anaerobe 2005; 11(5): 247–251CrossRefGoogle Scholar
  20. 20.
    Zhu Q, Jin Z, Wu W, Gao R, Guo B, Gao Z, Yang Y, Qin H. Analysis of the intestinal lumen microbiota in an animal model of colorectal cancer. PLoS One 2014; 9(6): e90849CrossRefGoogle Scholar
  21. 21.
    Wang T, Cai G, Qiu Y, Fei N, Zhang M, Pang X, Jia W, Cai S, Zhao L. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J 2012; 6(2): 320–329CrossRefGoogle Scholar
  22. 22.
    Tahara T, Yamamoto E, Suzuki H, Maruyama R, Chung W, Garriga J, Jelinek J, Yamano HO, Sugai T, An B, Shureiqi I, Toyota M, Kondo Y, Estécio MR, Issa JP. Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Res 2014; 74(5): 1311–1318CrossRefGoogle Scholar
  23. 23.
    McCoy AN, Araûjo-Pérez F, Azcárate-Peril A, Yeh JJ, Sandler RS, Keku TO. Fusobacterium is associated with colorectal adenomas. PLoS One 2013; 8(1): e53653CrossRefGoogle Scholar
  24. 24.
    Scanlan PD, Shanahan F, Clune Y, Collins JK, O’Sullivan GC, O’Riordan M, Holmes E, Wang Y, Marchesi JR. Culture-independent analysis of the gut microbiota in colorectal cancer and polyposis. Environ Microbiol 2008; 10(3): 789–798CrossRefGoogle Scholar
  25. 25.
    Sasada T, Hinoi T, Saito Y, Adachi T, Takakura Y, Kawaguchi Y, Sotomaru Y, Sentani K, Oue N, Yasui W, Ohdan H. Chlorinated water modulates the development of colorectal tumors with chromosomal instability and gut microbiota in APC-deficient mice. PLoS One 2015; 10(7): e0132435CrossRefGoogle Scholar
  26. 26.
    Turnbaugh PJ, Ley RE, Mahowald MA, Magrini V, Mardis ER, Gordon JI. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 2006; 444(7122): 1027–1031CrossRefGoogle Scholar
  27. 27.
    Scharlau D, Borowicki A, Habermann N, Hofmann T, Klenow S, Miene C, Munjal U, Stein K, Glei M. Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre. Mutat Res 2009; 682(1): 39–53CrossRefGoogle Scholar
  28. 28.
    Balamurugan R, Rajendiran E, George S, Samuel GV, Ramakrishna BS. Real-time polymerase chain reaction quantification of specific butyrate-producing bacteria, Desulfovibrio and Enterococcus faecalis in the feces of patients with colorectal cancer. J Gastroenterol Hepatol 2008; 23(8 Pt 1): 1298–1303CrossRefGoogle Scholar
  29. 29.
    Le Leu RK, Winter JM, Christophersen CT, Young GP, Humphreys KJ, Hu Y, Gratz SW, Miller RB, Topping DL, Bird AR, Conlon MA. Butyrylated starch intake can prevent red meat-induced O6-methyl-2-deoxyguanosine adducts in human rectal tissue: a randomised clinical trial. Br J Nutr 2015; 114(2): 220–230CrossRefGoogle Scholar
  30. 30.
    Duncan SH, Belenguer A, Holtrop G, Johnstone AM, Flint HJ, Lobley GE. Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl Environ Microbiol 2007; 73(4): 1073–1078CrossRefGoogle Scholar
  31. 31.
    Sengupta S, Muir JG, Gibson PR. Does butyrate protect from colorectal cancer? J Gastroenterol Hepatol 2006; 21(1 Pt 2): 209–218CrossRefGoogle Scholar
  32. 32.
    Sato I, Ito M, Ishizaka M, Ikunaga Y, Sato Y, Yoshida S, Koitabashi M, Tsushima S. Thirteen novel deoxynivalenol-degrading bacteria are classified within two genera with distinct degradation mechanisms. FEMS Microbiol Lett 2012; 327(2): 110–117CrossRefGoogle Scholar

Copyright information

© Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Hong Zhang
    • 1
  • Ying Chang
    • 2
  • Qingqing Zheng
    • 2
  • Rong Zhang
    • 1
  • Cheng Hu
    • 1
    Email author
  • Weiping Jia
    • 1
  1. 1.Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for DiabetesShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghaiChina
  2. 2.Digestive Endoscopic CenterShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghaiChina

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