Skip to main content

Diet, Gut Microbiota, and Colorectal Cancer Prevention: a Review of Potential Mechanisms and Promising Targets for Future Research

Current Colorectal Cancer Reports volume 13, pages 429–439 (2017)Cite this article

Abstract

Diet plays an important role in the development of colorectal cancer. Emerging data have implicated the gut microbiota in colorectal cancer. Diet is a major determinant for the gut microbial structure and function. Therefore, it has been hypothesized that alterations in gut microbes and their metabolites may contribute to the influence of diet on the development of colorectal cancer. We review several major dietary factors that have been linked to gut microbiota and colorectal cancer, including major dietary patterns, fiber, red meat and sulfur, and obesity. Most of the epidemiologic evidence derives from cross-sectional or short-term, highly controlled feeding studies that are limited in size. Therefore, high-quality large-scale prospective studies with dietary data collected over the life course and comprehensive gut microbial composition and function assessed well prior to neoplastic occurrence are critically needed to identify microbiome-based interventions that may complement or optimize current diet-based strategies for colorectal cancer prevention and management.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Ferlay J, Soerjomataram I, Ervik M, et al. Cancer incidence and mortality worldwide: IARC CancerBase No. 11 [Internet]. GLOBOCAN 2012 v1.0. Lyon: International Agency for Research on Cancer; 2013.

    Google Scholar 

  2. •• Song M, Garrett WS, Chan AT. Nutrients, foods, and colorectal cancer prevention. Gastroenterology. 2015;148:1244–1260 e16. A comprehensive review of epidemiologic and mechanistic evidence supporting the importance of nutritional factors in colorectal cancer prevention

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Scanlan PD, Shanahan F, Clune Y, et al. Culture-independent analysis of the gut microbiota in colorectal cancer and polyposis. Environ Microbiol. 2008;10:789–98.

    Article  CAS  PubMed  Google Scholar 

  4. Sobhani I, Tap J, Roudot-Thoraval F, et al. Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One. 2011;6:e16393.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Wang T, Cai G, Qiu Y, et al. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J. 2012;6:320–9.

    Article  CAS  PubMed  Google Scholar 

  6. Ahn J, Sinha R, Pei Z, et al. Human gut microbiome and risk for colorectal cancer. J Natl Cancer Inst. 2013;105:1907–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zackular JP, Rogers MA, Ruffin MT, et al. The human gut microbiome as a screening tool for colorectal cancer. Cancer Prev Res (Phila). 2014;7:1112–21.

    Article  CAS  Google Scholar 

  8. Zeller G, Tap J, Voigt AY, et al. Potential of fecal microbiota for early-stage detection of colorectal cancer. Mol Syst Biol. 2014;10:766.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Feng Q, Liang S, Jia H, et al. Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat Commun. 2015;6:6528.

    Article  CAS  PubMed  Google Scholar 

  10. Vogtmann E, Hua X, Zeller G, et al. Colorectal cancer and the human gut microbiome: reproducibility with whole-genome shotgun sequencing. PLoS One. 2016;11:e0155362.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Yu J, Feng Q, Wong SH, et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut. 2017;66:70–8.

    Article  PubMed  Google Scholar 

  12. Shah MS, DeSantis TZ, Weinmaier T, et al. Leveraging sequence-based faecal microbial community survey data to identify a composite biomarker for colorectal cancer. Gut. 2017.

  13. Liang Q, Chiu J, Chen Y, et al. Fecal bacteria act as novel biomarkers for noninvasive diagnosis of colorectal cancer. Clin Cancer Res. 2017;23:2061–70.

    Article  CAS  PubMed  Google Scholar 

  14. Flemer B, Lynch DB, Brown JM, et al. Tumour-associated and non-tumour-associated microbiota in colorectal cancer. Gut. 2017;66:633–43.

    Article  PubMed  Google Scholar 

  15. • Lasry A, Zinger A, Ben-Neriah Y. Inflammatory networks underlying colorectal cancer. Nat Immunol. 2016;17:230–40. An updated review of the inmportance of inflammatory components in colorectal cancer

    Article  CAS  PubMed  Google Scholar 

  16. Claesson MJ, Cusack S, O'Sullivan O, et al. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc Natl Acad Sci U S A. 2011;108(Suppl 1):4586–91.

    Article  CAS  PubMed  Google Scholar 

  17. Faith JJ, Guruge JL, Charbonneau M, et al. The long-term stability of the human gut microbiota. Science. 2013;341:1237439.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science. 2005;308:1635–8.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Costello EK, Lauber CL, Hamady M, et al. Bacterial community variation in human body habitats across space and time. Science. 2009;326:1694–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Jalanka-Tuovinen J, Salonen A, Nikkila J, et al. Intestinal microbiota in healthy adults: temporal analysis reveals individual and common core and relation to intestinal symptoms. PLoS One. 2011;6:e23035.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Rajilic-Stojanovic M, Heilig HG, Tims S, et al. Long-term monitoring of the human intestinal microbiota composition. Environ Microbiol. 2012;

  22. • David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559–63. A landmark study indicating that the gut microbiome can rapidly respond to altered diet

    Article  CAS  PubMed  Google Scholar 

  23. Wu GD, Chen J, Hoffmann C, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334:105–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lahti L, Salojarvi J, Salonen A, et al. Tipping elements in the human intestinal ecosystem. Nat Commun. 2014;5:4344.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Walter J. Murine gut microbiota-diet trumps genes. Cell Host Microbe. 2015;17:3–5.

    Article  CAS  PubMed  Google Scholar 

  26. •• O'Keefe SJ, Li JV, Lahti L, et al. Fat, fibre and cancer risk in African Americans and rural Africans. Nat Commun. 2015;6:6342. The study provides strong eivdence for the role of the gut microbiome in mediating the relationship between dietary factors and cancer risk

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. •• Zeevi D, Korem T, Zmora N, et al. Personalized nutrition by prediction of glycemic responses. Cell. 2015;163:1079–94. The study suggests that the gut microbiome is an important determinant for the inter-individual variation in the metabolic response to dietary intervention

    Article  CAS  PubMed  Google Scholar 

  28. Zmora N, Zeevi D, Korem T, et al. Taking it personally: personalized utilization of the human microbiome in health and disease. Cell Host Microbe. 2016;19:12–20.

    Article  CAS  PubMed  Google Scholar 

  29. Miller PE, Lesko SM, Muscat JE, et al. Dietary patterns and colorectal adenoma and cancer risk: a review of the epidemiological evidence. Nutr Cancer. 2010;62:413–24.

    Article  PubMed  Google Scholar 

  30. Magalhaes B, Peleteiro B, Lunet N. Dietary patterns and colorectal cancer: systematic review and meta-analysis. Eur J Cancer Prev. 2012;21:15–23.

    Article  CAS  PubMed  Google Scholar 

  31. Serino M, Luche E, Gres S, et al. Metabolic adaptation to a high-fat diet is associated with a change in the gut microbiota. Gut. 2012;61:543–53.

    Article  CAS  PubMed  Google Scholar 

  32. Martinez-Medina M, Denizot J, Dreux N, et al. Western diet induces dysbiosis with increased E coli in CEABAC10 mice, alters host barrier function favouring AIEC colonisation. Gut. 2014;63:116–24.

    Article  PubMed  CAS  Google Scholar 

  33. Ley SH, Sun Q, Willett WC, et al. Associations between red meat intake and biomarkers of inflammation and glucose metabolism in women. Am J Clin Nutr. 2014;99:352–60.

    Article  CAS  PubMed  Google Scholar 

  34. Schulze MB, Hoffmann K, Manson JE, et al. Dietary pattern, inflammation, and incidence of type 2 diabetes in women. Am J Clin Nutr. 2005;82:675–84. quiz 714-5

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Montonen J, Boeing H, Fritsche A, et al. Consumption of red meat and whole-grain bread in relation to biomarkers of obesity, inflammation, glucose metabolism and oxidative stress. Eur J Nutr. 2013;52:337–45.

    Article  CAS  PubMed  Google Scholar 

  36. Esmaillzadeh A, Kimiagar M, Mehrabi Y, et al. Dietary patterns and markers of systemic inflammation among Iranian women. J Nutr. 2007;137:992–8.

    CAS  PubMed  Google Scholar 

  37. Lopez-Garcia E, Schulze MB, Fung TT, et al. Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction. Am J Clin Nutr. 2004;80:1029–35.

    CAS  PubMed  Google Scholar 

  38. Brown K, DeCoffe D, Molcan E, et al. Diet-induced dysbiosis of the intestinal microbiota and the effects on immunity and disease. Nutrients. 2012;4:1095–119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Myles IA. Fast food fever: reviewing the impacts of the Western diet on immunity. Nutr J. 2014;13:61.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Kramer CD, Weinberg EO, Gower AC, et al. Distinct gene signatures in aortic tissue from ApoE−/− mice exposed to pathogens or Western diet. BMC Genomics. 2014;15:1176.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. 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. Proc Natl Acad Sci U S A. 2010;107:14691–6.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Ou J, Carbonero F, Zoetendal EG, et al. Diet, microbiota, and microbial metabolites in colon cancer risk in rural Africans and African Americans. Am J Clin Nutr. 2013;98:111–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Mehta RS, Nishihara R, Cao Y, et al. Association of dietary patterns with risk of colorectal cancer subtypes classified by Fusobacterium nucleatum in tumor tissue. JAMA Oncol. 2017;

  44. Abed J, Emgard JE, Zamir G, et al. Fap2 mediates Fusobacterium nucleatum colorectal adenocarcinoma enrichment by binding to tumor-expressed gal-GalNAc. Cell Host Microbe. 2016;20:215–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Castellarin M, Warren RL, Freeman JD, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012;22:299–306.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Kostic AD, Gevers D, Pedamallu CS, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012;22:292–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Tahara T, Yamamoto E, Suzuki H, et al. Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Res. 2014;74:1311–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Chen W, Liu F, Ling Z, et al. Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer. PLoS One. 2012;7:e39743.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. McCoy AN, Araujo-Perez F, Azcarate-Peril A, et al. Fusobacterium is associated with colorectal adenomas. PLoS One. 2013;8:e53653.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Allali I, Delgado S, Marron PI, et al. Gut microbiome compositional and functional differences between tumor and non-tumor adjacent tissues from cohorts from the US and Spain. Gut Microbes. 2015:0.

  51. Nakatsu G, Li X, Zhou H, et al. Gut mucosal microbiome across stages of colorectal carcinogenesis. Nat Commun. 2015;6:8727.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. • Mima K, Nishihara R, Qian ZR, et al. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut. 2016;65:1973–80. The study indicates that high abundance of Fusobacterium nucleatum in the tumor tissue is associated with worse survival of colorectal cancer, providing further support for the pro-colorectal cancer effect of this bacteria.

    Article  PubMed  Google Scholar 

  53. Kostic AD, Chun E, Robertson L, et al. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe. 2013;14:207–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. 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. Immunity. 2015;42:344–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Rubinstein MR, Wang X, Liu W, et al. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/beta-catenin signaling via its FadA adhesin. Cell Host Microbe. 2013;14:195–206.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. World Cancer Research Fund / American Institute for Cancer Research. Continuous Update Project report: food, nutrition, physical activity, and the prevention of colorectal cancer. 2011. http://www.wcrf.org/sites/default/files/Colorectal-Cancer-2011-Report.pdf.

  57. Anderson JW, Baird P, Davis RH Jr, et al. Health benefits of dietary fiber. Nutr Rev. 2009;67:188–205.

    Article  PubMed  Google Scholar 

  58. Pollak M. The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nat Rev Cancer. 2012;12:159–69.

    CAS  PubMed  Google Scholar 

  59. Giovannucci E, Michaud D. The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. Gastroenterology. 2007;132:2208–25.

    Article  CAS  PubMed  Google Scholar 

  60. Giovannucci E, Harlan DM, Archer MC, et al. Diabetes and cancer: a consensus report. CA Cancer J Clin. 2010;60:207–21.

    Article  PubMed  Google Scholar 

  61. Burkitt DP. Epidemiology of cancer of the colon and rectum. Cancer. 1971;28:3–13.

    Article  CAS  PubMed  Google Scholar 

  62. Chen HM, Yu YN, Wang JL, et al. Decreased dietary fiber intake and structural alteration of gut microbiota in patients with advanced colorectal adenoma. Am J Clin Nutr. 2013;97:1044–52.

    Article  CAS  PubMed  Google Scholar 

  63. Donohoe DR, Garge N, Zhang X, et al. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 2011;13:517–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Encarnacao JC, Abrantes AM, Pires AS, et al. Revisit dietary fiber on colorectal cancer: butyrate and its role on prevention and treatment. Cancer Metastasis Rev. 2015;34:465–78.

    Article  CAS  PubMed  Google Scholar 

  65. •• Donohoe DR, Holley D, Collins LB, et al. A gnotobiotic mouse model demonstrates that dietary fiber protects against colorectal tumorigenesis in a microbiota- and butyrate-dependent manner. Cancer Discov. 2014;4:1387–97. The study suggests a model of mechanisms by which dietary fiber may protect against colorectal cancer in a gut microbiota- and butyrate-dependent manner, and provides a potential explanation for inconsistent findings about the relationship of fiber intake and colorectal cancer risk reported in epidemiologic studies.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Tang Y, Chen Y, Jiang H, et al. G-protein-coupled receptor for short-chain fatty acids suppresses colon cancer. Int J Cancer. 2011;128:847–56.

    Article  CAS  PubMed  Google Scholar 

  67. Singh N, Gurav A, Sivaprakasam S, et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity. 2014;40:128–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Thangaraju M, Cresci GA, Liu K, et al. GPR109A is a G-protein-coupled receptor for the bacterial fermentation product butyrate and functions as a tumor suppressor in colon. Cancer Res. 2009;69:2826–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Arpaia N, Campbell C, Fan X, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504:451–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Furusawa Y, Obata Y, Fukuda S, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504:446–50.

    Article  CAS  PubMed  Google Scholar 

  71. Smith PM, Howitt MR, Panikov N, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341:569–73.

    Article  CAS  PubMed  Google Scholar 

  72. Chang PV, Hao L, Offermanns S, et al. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci U S A. 2014;111:2247–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Hu Y, Le Leu RK, Christophersen CT, et al. Manipulation of the gut microbiota using resistant starch is associated with protection against colitis-associated colorectal cancer in rats. Carcinogenesis. 2016;37:366–75.

    Article  CAS  PubMed  Google Scholar 

  74. Entin-Meer M, Rephaeli A, Yang X, et al. Butyric acid prodrugs are histone deacetylase inhibitors that show antineoplastic activity and radiosensitizing capacity in the treatment of malignant gliomas. Mol Cancer Ther. 2005;4:1952–61.

    Article  CAS  PubMed  Google Scholar 

  75. Kuefer R, Hofer MD, Altug V, et al. Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer. Br J Cancer. 2004;90:535–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Bras-Goncalves RA, Pocard M, Formento JL, et al. Synergistic efficacy of 3n-butyrate and 5-fluorouracil in human colorectal cancer xenografts via modulation of DNA synthesis. Gastroenterology. 2001;120:874–88.

    Article  CAS  PubMed  Google Scholar 

  77. • Belcheva A, Irrazabal T, Robertson SJ, et al. Gut microbial metabolism drives transformation of Msh2-deficient colon epithelial cells. Cell. 2014;158:288–99. The study suggests that the effect of fiber on colorectal cancer depends on the host genetic background, with a procancer effect in the context of MSH2 −/− .

    Article  CAS  PubMed  Google Scholar 

  78. Reitmair AH, Cai JC, Bjerknes M, et al. MSH2 deficiency contributes to accelerated APC-mediated intestinal tumorigenesis. Cancer Res. 1996;56:2922–6.

    CAS  PubMed  Google Scholar 

  79. World Cancer Research Fund / American Institute for Cancer Research. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Washington DC: AICR; 2007.

    Google Scholar 

  80. Cross AJ, Ferrucci LM, Risch A, et al. A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association. Cancer Res. 2010;70:2406–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Chan AT, Giovannucci EL. Primary prevention of colorectal cancer. Gastroenterology. 2010;138:2029–43. e10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Magee EA, Richardson CJ, Hughes R, et al. Contribution of dietary protein to sulfide production in the large intestine: an in vitro and a controlled feeding study in humans. Am J Clin Nutr. 2000;72:1488–94.

    CAS  PubMed  Google Scholar 

  83. Tilg H, Kaser A. Diet and relapsing ulcerative colitis: take off the meat? Gut. 2004;53:1399–401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Roediger WE, Moore J, Babidge W. Colonic sulfide in pathogenesis and treatment of ulcerative colitis. Dig Dis Sci. 1997;42:1571–9.

    Article  CAS  PubMed  Google Scholar 

  85. Rowan FE, Docherty NG, Coffey JC, et al. Sulphate-reducing bacteria and hydrogen sulphide in the aetiology of ulcerative colitis. Br J Surg. 2009;96:151–8.

    Article  CAS  PubMed  Google Scholar 

  86. Huycke MM, Gaskins HR. Commensal bacteria, redox stress, and colorectal cancer: mechanisms and models. Exp Biol Med. 2004;229:586–97.

    Article  CAS  Google Scholar 

  87. Deplancke B, Gaskins HR. Hydrogen sulfide induces serum-independent cell cycle entry in nontransformed rat intestinal epithelial cells. FASEB J. 2003;17:1310–2.

    CAS  PubMed  Google Scholar 

  88. Attene-Ramos MS, Wagner ED, Gaskins HR, et al. Hydrogen sulfide induces direct radical-associated DNA damage. Mol Cancer Res. 2007;5:455–9.

    Article  CAS  PubMed  Google Scholar 

  89. Ramasamy S, Singh S, Taniere P, et al. Sulfide-detoxifying enzymes in the human colon are decreased in cancer and upregulated in differentiation. Am J Physiol Gastrointest Liver Physiol. 2006;291:G288–96.

    Article  CAS  PubMed  Google Scholar 

  90. Cai WJ, Wang MJ, Ju LH, et al. Hydrogen sulfide induces human colon cancer cell proliferation: role of Akt, ERK and p21. Cell Biol Int. 2010;34:565–72.

    Article  CAS  PubMed  Google Scholar 

  91. Carbonero F, Benefiel AC, Gaskins HR.Contributions of the microbial hydrogen economy to colonic homeostasis Nature reviews. Gastroenterol Hepatol 2012;9:504–518.

  92. Wu YC, Wang XJ, Yu L, et al. Hydrogen sulfide lowers proliferation and induces protective autophagy in colon epithelial cells. PLoS One. 2012;7:e37572.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Roediger WE, Duncan A, Kapaniris O, et al. Reducing sulfur compounds of the colon impair colonocyte nutrition: implications for ulcerative colitis. Gastroenterology. 1993;104:802–9.

    Article  CAS  PubMed  Google Scholar 

  94. Pitcher MC, Beatty ER, Cummings JH. The contribution of sulphate reducing bacteria and 5-aminosalicylic acid to faecal sulphide in patients with ulcerative colitis. Gut. 2000;46:64–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Vinolo MA, Rodrigues HG, Hatanaka E, et al. Short-chain fatty acids stimulate the migration of neutrophils to inflammatory sites. Clin Sci. 2009;117:331–8.

    Article  CAS  PubMed  Google Scholar 

  96. Zeng H, Combs GF Jr. Selenium as an anticancer nutrient: roles in cell proliferation and tumor cell invasion. J Nutr Biochem. 2008;19:1–7.

    Article  PubMed  CAS  Google Scholar 

  97. Miller TW, Wang EA, Gould S, et al. Hydrogen sulfide is an endogenous potentiator of T cell activation. J Biol Chem. 2012;287:4211–21.

    Article  CAS  PubMed  Google Scholar 

  98. O'Keefe SJ, Ou J, Aufreiter S, et al. Products of the colonic microbiota mediate the effects of diet on colon cancer risk. J Nutr. 2009;139:2044–8.

    Article  PubMed  CAS  Google Scholar 

  99. Bianchini F, Vainio H. Isothiocyanates in cancer prevention. Drug Metab Rev. 2004;36:655–67.

    Article  CAS  PubMed  Google Scholar 

  100. Carbonero F, Benefiel AC, Alizadeh-Ghamsari AH, et al. Microbial pathways in colonic sulfur metabolism and links with health and disease. Front Physiol. 2012;3:448.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Larsson SC, Kumlin M, Ingelman-Sundberg M, et al. Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms. Am J Clin Nutr. 2004;79:935–45.

    CAS  PubMed  Google Scholar 

  102. Cockbain AJ, Toogood GJ, Hull MA. Omega-3 polyunsaturated fatty acids for the treatment and prevention of colorectal cancer. Gut. 2012;61:135–49.

    Article  CAS  PubMed  Google Scholar 

  103. Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol. 2008;8:349–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. •• Cockbain AJ, Volpato M, Race AD, et al. Anticolorectal cancer activity of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid. Gut. 2014;63:1760–8. This randomized controlled study supports the chemopreventive effect of omega-3 fatty acid supplementation on colorectal cancer.

    Article  CAS  PubMed  Google Scholar 

  105. Clarke TC, Black LI, Stussman BJ, et al. Trends in the use of complementary health approaches among adults: United States, 2002–2012. Natl. Health Stat. Rep. 2015:1–16.

  106. West NJ, Clark SK, Phillips RK, et al. Eicosapentaenoic acid reduces rectal polyp number and size in familial adenomatous polyposis. Gut. 2010;59:918–25.

    Article  CAS  PubMed  Google Scholar 

  107. Calder PC. Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim Biophys Acta. 1851;2015:469–84.

    Google Scholar 

  108. Piazzi G, D'Argenio G, Prossomariti A, et al. Eicosapentaenoic acid free fatty acid prevents and suppresses colonic neoplasia in colitis-associated colorectal cancer acting on Notch signaling and gut microbiota. J Int Cancer. 2014;135:2004–13.

    Article  CAS  Google Scholar 

  109. Jiang Y, Djuric Z, Sen A, et al. Biomarkers for personalizing omega-3 fatty acid dosing. Cancer Prev Res (Phila). 2014;7:1011–22.

    Article  CAS  Google Scholar 

  110. Calviello G, Di Nicuolo F, Gragnoli S, et al. n-3 PUFAs reduce VEGF expression in human colon cancer cells modulating the COX-2/PGE2 induced ERK-1 and -2 and HIF-1alpha induction pathway. Carcinogenesis. 2004;25:2303–10.

    Article  CAS  PubMed  Google Scholar 

  111. Bartram HP, Gostner A, Scheppach W, et al. Effects of fish oil on rectal cell proliferation, mucosal fatty acids, and prostaglandin E2 release in healthy subjects. Gastroenterology. 1993;105:1317–22.

    Article  CAS  PubMed  Google Scholar 

  112. Nowak J, Weylandt KH, Habbel P, et al. Colitis-associated colon tumorigenesis is suppressed in transgenic mice rich in endogenous n-3 fatty acids. Carcinogenesis. 2007;28:1991–5.

    Article  CAS  PubMed  Google Scholar 

  113. • Song M, Nishihara R, Cao Y, et al. Marine omega-3 polyunsaturated fatty acid intake and risk of colorectal cancer characterized by tumor-infiltrating T cells. JAMA Oncol. 2016;2:1197–206. This study suggests that the beneficial effect of high omega-3 fatty acid intake may be partly mediated by modulation of regulatory T cells in the tumor microenvironment.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Caesar R, Tremaroli V, Kovatcheva-Datchary P, et al. Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR signaling. Cell Metab. 2015;22:658–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Devkota S, Wang Y, Musch MW, et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10 −/− mice. Nature. 2012;487:104–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Ghosh S, DeCoffe D, Brown K, et al. Fish oil attenuates omega-6 polyunsaturated fatty acid-induced dysbiosis and infectious colitis but impairs LPS dephosphorylation activity causing sepsis. PLoS One. 2013;8:e55468.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Patterson E, RM OD, Murphy EF, et al. Impact of dietary fatty acids on metabolic activity and host intestinal microbiota composition in C57BL/6J mice. Br J Nutr. 2014;1–13.

  118. Mujico JR, Baccan GC, Gheorghe A, et al. Changes in gut microbiota due to supplemented fatty acids in diet-induced obese mice. Br J Nutr. 2013;110:711–20.

    Article  CAS  PubMed  Google Scholar 

  119. Shen W, Gaskins HR, McIntosh MK. Influence of dietary fat on intestinal microbes, inflammation, barrier function and metabolic outcomes. J Nutr Biochem. 2014;25:270–80.

    Article  CAS  PubMed  Google Scholar 

  120. Ghosh S, Molcan E, DeCoffe D, et al. Diets rich in n-6 PUFA induce intestinal microbial dysbiosis in aged mice. Br J Nutr. 2013;110:515–23.

    Article  CAS  PubMed  Google Scholar 

  121. Kaliannan K, Wang B, Li XY, et al. Omega-3 fatty acids prevent early-life antibiotic exposure-induced gut microbiota dysbiosis and later-life obesity. Int J Obes (Lond). 2016.

  122. Jenq RR, Ubeda C, Taur Y, et al. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J Exp Med. 2012;209:903–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Peran L, Sierra S, Comalada M, et al. A comparative study of the preventative effects exerted by two probiotics, Lactobacillus reuteri and Lactobacillus fermentum, in the trinitrobenzenesulfonic acid model of rat colitis. Br J Nutr. 2007;97:96–103.

    Article  CAS  PubMed  Google Scholar 

  124. Khazaie K, Zadeh M, Khan MW, et al. Abating colon cancer polyposis by Lactobacillus acidophilus deficient in lipoteichoic acid. Proc Natl Acad Sci U S A. 2012;109:10462–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. • Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350:1084–9. The study indicates that the efficacy of cancer immunotherapy may depend on the abundance of Bifidobacterium in the gut.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Iida N, Dzutsev A, Stewart CA, et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science. 2013;342:967–70.

    Article  CAS  PubMed  Google Scholar 

  127. Kishino S, Takeuchi M, Park SB, et al. Polyunsaturated fatty acid saturation by gut lactic acid bacteria affecting host lipid composition. Proc Natl Acad Sci U S A. 2013;110:17808–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Kishino S, Ogawa J, Yokozeki K, et al. Metabolic diversity in biohydrogenation of polyunsaturated fatty acids by lactic acid bacteria involving conjugated fatty acid production. Appl Microbiol Biotechnol. 2009;84:87–97.

    Article  CAS  PubMed  Google Scholar 

  129. Hirata A, Kishino S, Park SB, et al. A novel unsaturated fatty acid hydratase toward C16 to C22 fatty acids from Lactobacillus acidophilus. J Lipid Res. 2015;56:1340–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Desbois AP, Smith VJ. Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential. Appl Microbiol Biotechnol. 2010;85:1629–42.

    Article  CAS  PubMed  Google Scholar 

  131. Sakurama H, Kishino S, Mihara K, et al. Biohydrogenation of C20 polyunsaturated fatty acids by anaerobic bacteria. J Lipid Res. 2014;55:1855–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Druart C, Bindels LB, Schmaltz R, et al. Ability of the gut microbiota to produce PUFA-derived bacterial metabolites: proof of concept in germ-free versus conventionalized mice. Mol Nutr Food Res. 2015;59:1603–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Druart C, Neyrinck AM, Vlaeminck B, et al. Role of the lower and upper intestine in the production and absorption of gut microbiota-derived PUFA metabolites. PLoS One. 2014;9:e87560.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  134. Furumoto H, Nanthirudjanar T, Kume T, et al. 10-Oxo-trans-11-octadecenoic acid generated from linoleic acid by a gut lactic acid bacterium Lactobacillus plantarum is cytoprotective against oxidative stress. Toxicol Appl Pharmacol. 2016;296:1–9.

    Article  CAS  PubMed  Google Scholar 

  135. Miyamoto J, Mizukure T, Park SB, et al. A gut microbial metabolite of linoleic acid, 10-hydroxy-cis-12-octadecenoic acid, ameliorates intestinal epithelial barrier impairment partially via GPR40-MEK-ERK pathway. J Biol Chem. 2015;290:2902–18.

    Article  CAS  PubMed  Google Scholar 

  136. Flint HJ, Duncan SH, Scott KP, et al. Links between diet, gut microbiota composition and gut metabolism. Proc Nutr Soc. 2015;74:13–22.

    Article  CAS  PubMed  Google Scholar 

  137. Belenguer A, Duncan SH, Calder AG, et al. Two routes of metabolic cross-feeding between Bifidobacterium adolescentis and butyrate-producing anaerobes from the human gut. Appl Environ Microbiol. 2006;72:3593–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Duncan SH, Louis P, Flint HJ. Lactate-utilizing bacteria, isolated from human feces, that produce butyrate as a major fermentation product. Appl Environ Microbiol. 2004;70:5810–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Arpaia N, Rudensky AY. Microbial metabolites control gut inflammatory responses. Proc Natl Acad Sci U S A. 2014;111:2058–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. O'Keefe SJ. Diet, microorganisms and their metabolites, and colon cancer. Nat Rev Gastroenterol Hepatol. 2016;13:691–706.

    Article  PubMed  CAS  Google Scholar 

  141. Kong SY, Tran HQ, Gewirtz AT, et al. Serum endotoxins and flagellin and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort. Cancer Epidemiol Biomark Prev. 2016;25:291–301.

    Article  CAS  Google Scholar 

  142. •• Kaliannan K, Wang B, Li XY, et al. A host-microbiome interaction mediates the opposing effects of omega-6 and omega-3 fatty acids on metabolic endotoxemia. Sci Rep. 2015;5:11276. The study proposes a model of mechanisms by which omega-3 fatty acid may influence the gut microbial composition through the influence on epithelial production of intestinal alkaline phosphatase.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Campbell EL, MacManus CF, Kominsky DJ, et al. Resolvin E1-induced intestinal alkaline phosphatase promotes resolution of inflammation through LPS detoxification. Proc Natl Acad Sci U S A. 2010;107:14298–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Polan CE, McNeill JJ, Tove SB. Biohydrogenation of unsaturated fatty acids by rumen bacteria. J Bacteriol. 1964;88:1056–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Tilg H, Moschen AR. Food, immunity, and the microbiome. Gastroenterology. 2015;148:1107–19.

    Article  PubMed  Google Scholar 

  146. Finucane MM, Stevens GA, Cowan MJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet. 2011;377:557–67.

    Article  PubMed  PubMed Central  Google Scholar 

  147. Swinburn BA, Sacks G, Hall KD, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet. 2011;378:804–14.

    Article  PubMed  Google Scholar 

  148. Malik VS, Willett WC, Hu FB. Global obesity: trends, risk factors and policy implications. Nat. Rev. Endocrinol. 2013;9:13–27.

    Article  PubMed  Google Scholar 

  149. Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body fatness and cancer—viewpoint of the IARC Working Group. N Engl J Med. 2016;375:794–8.

    Article  PubMed  Google Scholar 

  150. Doyle SL, Donohoe CL, Lysaght J, et al. Visceral obesity, metabolic syndrome, insulin resistance and cancer. Proc Nutr Soc. 2012;71:181–9.

    Article  CAS  PubMed  Google Scholar 

  151. Renehan AG, Zwahlen M, Egger M. Adiposity and cancer risk: new mechanistic insights from epidemiology. Nat Rev Cancer. 2015;15:484–98.

    Article  CAS  PubMed  Google Scholar 

  152. Ley RE, Turnbaugh PJ, Klein S, et al. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444:1022–3.

    Article  CAS  PubMed  Google Scholar 

  153. Furet JP, Kong LC, Tap J, et al. Differential adaptation of human gut microbiota to bariatric surgery-induced weight loss: links with metabolic and low-grade inflammation markers. Diabetes. 2010;59:3049–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Ley RE, Backhed F, Turnbaugh P, et al. Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A. 2005;102:11070–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Duncan SH, Lobley GE, Holtrop G, et al. Human colonic microbiota associated with diet, obesity and weight loss. Int J Obes. 2008;32:1720–4.

    Article  CAS  Google Scholar 

  156. Backhed F, Ding H, Wang T, et al. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004;101:15718–23.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  157. Turnbaugh PJ, Ley RE, Mahowald MA, et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature. 2006;444:1027–31.

    Article  PubMed  Google Scholar 

  158. Turnbaugh PJ, Backhed F, Fulton L, et al. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe. 2008;3:213–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  159. Cox LM, Blaser MJ. Antibiotics in early life and obesity. Nat. Rev. Endocrinol. 2015;11:182–90.

    Article  PubMed  Google Scholar 

  160. • Cox LM, Yamanishi S, Sohn J, et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell. 2014;158:705–21. The study suggests that disturbances of the gut microbiome in early life may contribute to subsequent development of obesity in later life.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Cao Y, Wu K, Mehta R, et al. Long-term use of antibiotics and risk of colorectal adenoma. Gut. 2017.

  162. Kilkkinen A, Rissanen H, Klaukka T, et al. Antibiotic use predicts an increased risk of cancer. Int J Cancer. 2008;123:2152–5.

    Article  CAS  PubMed  Google Scholar 

  163. Boursi B, Haynes K, Mamtani R, et al. Impact of antibiotic exposure on the risk of colorectal cancer. Pharmacoepidemiol Drug Saf. 2015;24:534–42.

    Article  CAS  PubMed  Google Scholar 

  164. Dik VK, van Oijen MG, Smeets HM, et al. Frequent use of antibiotics is associated with colorectal cancer risk: results of a nested case-control study. Dig Dis Sci. 2016;61:255–64.

    Article  CAS  PubMed  Google Scholar 

  165. Musso G, Gambino R, Cassader M. Obesity, diabetes, and gut microbiota: the hygiene hypothesis expanded? Diabetes Care. 2010;33:2277–84.

    Article  PubMed  PubMed Central  Google Scholar 

  166. Duca FA, Lam TK. Gut microbiota, nutrient sensing and energy balance. Diabetes Obes Metab. 2014;16(Suppl 1):68–76.

    Article  PubMed  Google Scholar 

  167. Cox LM, Blaser MJ. Pathways in microbe-induced obesity. Cell Metab. 2013;17:883–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Song M, Willett WC, Hu FB, et al. Trajectory of body shape across the lifespan and cancer risk. Int J Cancer. 2016;138:2383–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  169. Yoshimoto S, Loo TM, Atarashi K, et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature. 2013;499:97–101.

    Article  CAS  PubMed  Google Scholar 

  170. Ohtani N, Yoshimoto S, Hara E. Obesity and cancer: a gut microbial connection. Cancer Res. 2014;74:1885–9.

    Article  CAS  PubMed  Google Scholar 

  171. •• Loo TM, Kamachi F, Watanabe Y, et al. Gut microbiota promotes obesity-associated liver cancer through PGE2-mediated suppression of antitumor immunity. Cancer Discov. 2017. The study provides new evidence about how obesity may promote liver cancer through an influence on the functionality of the gut microbiota.

  172. Wang D, DuBois RN. An inflammatory mediator, prostaglandin E2, in colorectal cancer. Cancer J. 2013;19:502–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  173. Wang D, DuBois RN. PPARdelta and PGE2 signaling pathways communicate and connect inflammation to colorectal cancer. Inflamm Cell Signal. 2014;1.

  174. Ajouz H, Mukherji D, Shamseddine A. Secondary bile acids: an underrecognized cause of colon cancer. World J. Surg. Oncol. 2014;12:164.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Bartlett Ext. 9, 55 Fruit Street, Boston, MA, 02114, USA

    Mingyang Song & Andrew T. Chan

  2. Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA

    Mingyang Song & Andrew T. Chan

  3. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA

    Mingyang Song

  4. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA, USA

    Andrew T. Chan

  5. Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA

    Andrew T. Chan

Authors
  1. Mingyang Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrew T. Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mingyang Song.

Ethics declarations

Conflict of Interest

The authors declare they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Nutrition and Nutritional Interventions in Colorectal Cancer

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Song, M., Chan, A.T. Diet, Gut Microbiota, and Colorectal Cancer Prevention: a Review of Potential Mechanisms and Promising Targets for Future Research. Curr Colorectal Cancer Rep 13, 429–439 (2017). https://doi.org/10.1007/s11888-017-0389-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11888-017-0389-y

Keywords

  • Gut microbiome
  • Antibiotics
  • Dietary pattern
  • Fiber
  • Red meat
  • Processed meat
  • Sulfur
  • Obesity
  • Short-chain fatty acid
  • Hydrogen sulfide
  • Sulfur-reducing bacteria
  • Fusobacterium nucleatum
  • Colorectal neoplasia