Current Colorectal Cancer Reports

, Volume 13, Issue 6, pp 429–439 | Cite as

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

  • Mingyang SongEmail author
  • Andrew T. Chan
Nutrition and Nutritional Interventions in Colorectal Cancer (K Wu, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Nutrition and Nutritional Interventions in Colorectal Cancer


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.


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 


Compliance with Ethical Standards

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.


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

  1. 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. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  3. 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.PubMedCrossRefGoogle Scholar
  4. 4.
    Sobhani I, Tap J, Roudot-Thoraval F, et al. Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One. 2011;6:e16393.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 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.CrossRefGoogle Scholar
  8. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Feng Q, Liang S, Jia H, et al. Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat Commun. 2015;6:6528.PubMedCrossRefGoogle Scholar
  10. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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.Google Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 14.
    Flemer B, Lynch DB, Brown JM, et al. Tumour-associated and non-tumour-associated microbiota in colorectal cancer. Gut. 2017;66:633–43.PubMedCrossRefGoogle Scholar
  15. 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 PubMedCrossRefGoogle Scholar
  16. 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.PubMedCrossRefGoogle Scholar
  17. 17.
    Faith JJ, Guruge JL, Charbonneau M, et al. The long-term stability of the human gut microbiota. Science. 2013;341:1237439.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science. 2005;308:1635–8.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  20. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Rajilic-Stojanovic M, Heilig HG, Tims S, et al. Long-term monitoring of the human intestinal microbiota composition. Environ Microbiol. 2012;Google Scholar
  22. 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 PubMedCrossRefGoogle Scholar
  23. 23.
    Wu GD, Chen J, Hoffmann C, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334:105–8.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Lahti L, Salojarvi J, Salonen A, et al. Tipping elements in the human intestinal ecosystem. Nat Commun. 2014;5:4344.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Walter J. Murine gut microbiota-diet trumps genes. Cell Host Microbe. 2015;17:3–5.PubMedCrossRefGoogle Scholar
  26. 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 PubMedPubMedCentralCrossRefGoogle Scholar
  27. 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 PubMedCrossRefGoogle Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 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.PubMedCrossRefGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 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 714-5PubMedPubMedCentralGoogle Scholar
  35. 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.PubMedCrossRefGoogle Scholar
  36. 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.PubMedGoogle Scholar
  37. 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.PubMedGoogle Scholar
  38. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Myles IA. Fast food fever: reviewing the impacts of the Western diet on immunity. Nutr J. 2014;13:61.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 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;Google Scholar
  44. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Castellarin M, Warren RL, Freeman JD, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012;22:299–306.PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Kostic AD, Gevers D, Pedamallu CS, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012;22:292–8.PubMedPubMedCentralCrossRefGoogle Scholar
  47. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    McCoy AN, Araujo-Perez F, Azcarate-Peril A, et al. Fusobacterium is associated with colorectal adenomas. PLoS One. 2013;8:e53653.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 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.Google Scholar
  51. 51.
    Nakatsu G, Li X, Zhou H, et al. Gut mucosal microbiome across stages of colorectal carcinogenesis. Nat Commun. 2015;6:8727.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 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. PubMedCrossRefGoogle Scholar
  53. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  54. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  55. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 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.
  57. 57.
    Anderson JW, Baird P, Davis RH Jr, et al. Health benefits of dietary fiber. Nutr Rev. 2009;67:188–205.PubMedCrossRefGoogle Scholar
  58. 58.
    Pollak M. The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nat Rev Cancer. 2012;12:159–69.PubMedGoogle Scholar
  59. 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.PubMedCrossRefGoogle Scholar
  60. 60.
    Giovannucci E, Harlan DM, Archer MC, et al. Diabetes and cancer: a consensus report. CA Cancer J Clin. 2010;60:207–21.PubMedCrossRefGoogle Scholar
  61. 61.
    Burkitt DP. Epidemiology of cancer of the colon and rectum. Cancer. 1971;28:3–13.PubMedCrossRefGoogle Scholar
  62. 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.PubMedCrossRefGoogle Scholar
  63. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 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.PubMedCrossRefGoogle Scholar
  65. 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. PubMedPubMedCentralCrossRefGoogle Scholar
  66. 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.PubMedCrossRefGoogle Scholar
  67. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  69. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 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.PubMedCrossRefGoogle Scholar
  71. 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.PubMedCrossRefGoogle Scholar
  72. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  73. 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.PubMedCrossRefGoogle Scholar
  74. 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.PubMedCrossRefGoogle Scholar
  75. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 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.PubMedCrossRefGoogle Scholar
  77. 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 −/− . PubMedCrossRefGoogle Scholar
  78. 78.
    Reitmair AH, Cai JC, Bjerknes M, et al. MSH2 deficiency contributes to accelerated APC-mediated intestinal tumorigenesis. Cancer Res. 1996;56:2922–6.PubMedGoogle Scholar
  79. 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. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Chan AT, Giovannucci EL. Primary prevention of colorectal cancer. Gastroenterology. 2010;138:2029–43. e10PubMedPubMedCentralCrossRefGoogle Scholar
  82. 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.PubMedGoogle Scholar
  83. 83.
    Tilg H, Kaser A. Diet and relapsing ulcerative colitis: take off the meat? Gut. 2004;53:1399–401.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Roediger WE, Moore J, Babidge W. Colonic sulfide in pathogenesis and treatment of ulcerative colitis. Dig Dis Sci. 1997;42:1571–9.PubMedCrossRefGoogle Scholar
  85. 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.PubMedCrossRefGoogle Scholar
  86. 86.
    Huycke MM, Gaskins HR. Commensal bacteria, redox stress, and colorectal cancer: mechanisms and models. Exp Biol Med. 2004;229:586–97.CrossRefGoogle Scholar
  87. 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.PubMedGoogle Scholar
  88. 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.PubMedCrossRefGoogle Scholar
  89. 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.PubMedCrossRefGoogle Scholar
  90. 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.PubMedCrossRefGoogle Scholar
  91. 91.
    Carbonero F, Benefiel AC, Gaskins HR.Contributions of the microbial hydrogen economy to colonic homeostasis Nature reviews. Gastroenterol Hepatol 2012;9:504–518.Google Scholar
  92. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 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.PubMedCrossRefGoogle Scholar
  94. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 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.PubMedCrossRefGoogle Scholar
  96. 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.PubMedCrossRefGoogle Scholar
  97. 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.PubMedCrossRefGoogle Scholar
  98. 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.PubMedCrossRefGoogle Scholar
  99. 99.
    Bianchini F, Vainio H. Isothiocyanates in cancer prevention. Drug Metab Rev. 2004;36:655–67.PubMedCrossRefGoogle Scholar
  100. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 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.PubMedGoogle Scholar
  102. 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.PubMedCrossRefGoogle Scholar
  103. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 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. PubMedCrossRefGoogle Scholar
  105. 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.Google Scholar
  106. 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.PubMedCrossRefGoogle Scholar
  107. 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. 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.CrossRefGoogle Scholar
  109. 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.CrossRefGoogle Scholar
  110. 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.PubMedCrossRefGoogle Scholar
  111. 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.PubMedCrossRefGoogle Scholar
  112. 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.PubMedCrossRefGoogle Scholar
  113. 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. PubMedPubMedCentralCrossRefGoogle Scholar
  114. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  115. 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.PubMedPubMedCentralGoogle Scholar
  116. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  117. 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.Google Scholar
  118. 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.PubMedCrossRefGoogle Scholar
  119. 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.PubMedCrossRefGoogle Scholar
  120. 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.PubMedCrossRefGoogle Scholar
  121. 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.Google Scholar
  122. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  123. 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.PubMedCrossRefGoogle Scholar
  124. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  125. 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. PubMedPubMedCentralCrossRefGoogle Scholar
  126. 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.PubMedCrossRefGoogle Scholar
  127. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  128. 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.PubMedCrossRefGoogle Scholar
  129. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  130. 130.
    Desbois AP, Smith VJ. Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential. Appl Microbiol Biotechnol. 2010;85:1629–42.PubMedCrossRefGoogle Scholar
  131. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  132. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  133. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  134. 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.PubMedCrossRefGoogle Scholar
  135. 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.PubMedCrossRefGoogle Scholar
  136. 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.PubMedCrossRefGoogle Scholar
  137. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  138. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  139. 139.
    Arpaia N, Rudensky AY. Microbial metabolites control gut inflammatory responses. Proc Natl Acad Sci U S A. 2014;111:2058–9.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    O'Keefe SJ. Diet, microorganisms and their metabolites, and colon cancer. Nat Rev Gastroenterol Hepatol. 2016;13:691–706.PubMedCrossRefGoogle Scholar
  141. 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.CrossRefGoogle Scholar
  142. 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. PubMedPubMedCentralCrossRefGoogle Scholar
  143. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  144. 144.
    Polan CE, McNeill JJ, Tove SB. Biohydrogenation of unsaturated fatty acids by rumen bacteria. J Bacteriol. 1964;88:1056–64.PubMedPubMedCentralGoogle Scholar
  145. 145.
    Tilg H, Moschen AR. Food, immunity, and the microbiome. Gastroenterology. 2015;148:1107–19.PubMedCrossRefGoogle Scholar
  146. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 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.PubMedCrossRefGoogle Scholar
  148. 148.
    Malik VS, Willett WC, Hu FB. Global obesity: trends, risk factors and policy implications. Nat. Rev. Endocrinol. 2013;9:13–27.PubMedCrossRefGoogle Scholar
  149. 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.PubMedCrossRefGoogle Scholar
  150. 150.
    Doyle SL, Donohoe CL, Lysaght J, et al. Visceral obesity, metabolic syndrome, insulin resistance and cancer. Proc Nutr Soc. 2012;71:181–9.PubMedCrossRefGoogle Scholar
  151. 151.
    Renehan AG, Zwahlen M, Egger M. Adiposity and cancer risk: new mechanistic insights from epidemiology. Nat Rev Cancer. 2015;15:484–98.PubMedCrossRefGoogle Scholar
  152. 152.
    Ley RE, Turnbaugh PJ, Klein S, et al. Microbial ecology: human gut microbes associated with obesity. Nature. 2006;444:1022–3.PubMedCrossRefGoogle Scholar
  153. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  155. 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.CrossRefGoogle Scholar
  156. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  157. 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.PubMedCrossRefGoogle Scholar
  158. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  159. 159.
    Cox LM, Blaser MJ. Antibiotics in early life and obesity. Nat. Rev. Endocrinol. 2015;11:182–90.PubMedCrossRefGoogle Scholar
  160. 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. PubMedPubMedCentralCrossRefGoogle Scholar
  161. 161.
    Cao Y, Wu K, Mehta R, et al. Long-term use of antibiotics and risk of colorectal adenoma. Gut. 2017.Google Scholar
  162. 162.
    Kilkkinen A, Rissanen H, Klaukka T, et al. Antibiotic use predicts an increased risk of cancer. Int J Cancer. 2008;123:2152–5.PubMedCrossRefGoogle Scholar
  163. 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.PubMedCrossRefGoogle Scholar
  164. 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.PubMedCrossRefGoogle Scholar
  165. 165.
    Musso G, Gambino R, Cassader M. Obesity, diabetes, and gut microbiota: the hygiene hypothesis expanded? Diabetes Care. 2010;33:2277–84.PubMedPubMedCentralCrossRefGoogle Scholar
  166. 166.
    Duca FA, Lam TK. Gut microbiota, nutrient sensing and energy balance. Diabetes Obes Metab. 2014;16(Suppl 1):68–76.PubMedCrossRefGoogle Scholar
  167. 167.
    Cox LM, Blaser MJ. Pathways in microbe-induced obesity. Cell Metab. 2013;17:883–94.PubMedPubMedCentralCrossRefGoogle Scholar
  168. 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.PubMedPubMedCentralCrossRefGoogle Scholar
  169. 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.PubMedCrossRefGoogle Scholar
  170. 170.
    Ohtani N, Yoshimoto S, Hara E. Obesity and cancer: a gut microbial connection. Cancer Res. 2014;74:1885–9.PubMedCrossRefGoogle Scholar
  171. 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. Google Scholar
  172. 172.
    Wang D, DuBois RN. An inflammatory mediator, prostaglandin E2, in colorectal cancer. Cancer J. 2013;19:502–10.PubMedPubMedCentralCrossRefGoogle Scholar
  173. 173.
    Wang D, DuBois RN. PPARdelta and PGE2 signaling pathways communicate and connect inflammation to colorectal cancer. Inflamm Cell Signal. 2014;1.Google Scholar
  174. 174.
    Ajouz H, Mukherji D, Shamseddine A. Secondary bile acids: an underrecognized cause of colon cancer. World J. Surg. Oncol. 2014;12:164.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Clinical and Translational Epidemiology UnitMassachusetts General Hospital and Harvard Medical SchoolBostonUSA
  2. 2.Division of GastroenterologyMassachusetts General HospitalBostonUSA
  3. 3.Department of NutritionHarvard T.H. Chan School of Public HealthBostonUSA
  4. 4.Channing Division of Network Medicine, Department of MedicineBrigham and Women’s Hospital, and Harvard Medical SchoolBostonUSA
  5. 5.Broad Institute of Massachusetts Institute of Technology and HarvardCambridgeUSA

Personalised recommendations