Fiber, Fat, and Colorectal Cancer: New Insight into Modifiable Dietary Risk Factors

  • Soeren Ocvirk
  • Annette S. Wilson
  • Corynn N. Appolonia
  • Timothy K. Thomas
  • Stephen J. D. O’KeefeEmail author
GI Oncology (R Bresalier, Section Editor)
Part of the following topical collections:
  1. Topical Collection on GI Oncology


Purpose of Review

To review recent data on the role and interactions of fiber and fat as dietary risk factors associated with colorectal cancer (CRC) risk in humans.

Recent Findings

Fiber intake shows convincing and linear dose-response negative correlation with CRC risk. Dietary fiber stimulates butyrogenic activity of the gut microbiota, providing high amounts of butyrate that shows extensive anti-neoplastic effects. A high-fat diet promotes CRC risk through stimulated bile acid metabolism, facilitating bile acid conversion by the gut microbiota to tumor-promoting deoxycholic acid. Comprehensive interactions of these microbial metabolites are likely to underlie mechanisms driving diet-dependent CRC risk in different populations, but require further experimental investigation.


Dietary fiber and fat shape the composition and metabolic function of the gut microbiota, resulting in altered amounts of butyrate and deoxycholic acid in the colon. Fiber supplementation and restriction of fat intake represent promising strategies to reduce CRC risk in healthy individuals.


Colorectal cancer risk Fiber Fat Butyrate Bile acids Gut microbiota 



We wish to thank the administration and outpatient clinic and pharmacy staffs at the Alaska Native Medical Center in Anchorage, Alaska, and Manguzi Hospital in Manguzi, KwaZulu-Natal, South Africa, for their support of the project. We also thank all participants for their willingness to participate in the study.

Funding Information

Soeren Ocvirk is supported by the German Research Foundation (Deutsche Forschungsgemeinschaft, 338582098). Stephen JD O’Keefe is supported by the National Institutes of Health (R01 CA204403).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

Fecal samples, used for preparation of water extracts, were taken during previous studies, where ethical and health research approval was obtained from all institutional review boards of all participating medical centers and health research entities. Informed consent was acquired before enrollment of study participants.


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

  1. 1.
    Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–86.CrossRefGoogle Scholar
  2. 2.
    Arnold M, Sierra MS, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global patterns and trends in colorectal cancer incidence and mortality. Gut. 2017;66:683–91.PubMedGoogle Scholar
  3. 3.
    Jasperson KW, Tuohy TM, Neklason DW, Burt RW. Hereditary and familial colon cancer. Gastroenterology. 2010;138:2044–58.PubMedPubMedCentralGoogle Scholar
  4. 4.
    O’Keefe SJD. Diet, microorganisms and their metabolites, and colon cancer. Nat Rev Gastroenterol Hepatol. 2016;13:691–706.PubMedPubMedCentralGoogle Scholar
  5. 5.
    •• Reynolds A, Mann J, Cummings J, Winter N, Mete E, Morenga LT. Carbohydrate quality and human health: a series of systematic reviews and meta-analyses. The Lancet. 2019. Comprehensive meta-analysis of observational studies and clinical trials, showing an inverse correlation of dietary fiber intake or whole grain intake, respectively, and CRC risk. CRC risk reduction is greatest for highest intake of dietary fiber or whole grain, respectively, and linear dose-response relationships suggest even greater effects on CRC risk reduction for higher intakes. Google Scholar
  6. 6.
    Kunzmann AT, Coleman HG, Huang W-Y, Kitahara CM, Cantwell MM, Berndt SI. Dietary fiber intake and risk of colorectal cancer and incident and recurrent adenoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Clin Nutr. 2015;102:881–90.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Llewellyn SR, Britton GJ, Contijoch EJ, Vennaro OH, Mortha A, Colombel J-F, et al. Interactions between diet and the intestinal microbiota alter intestinal permeability and colitis severity in mice. Gastroenterology. 2018;154:1037–1046.e2.PubMedGoogle Scholar
  8. 8.
    •• O’Keefe SJD, Li JV, Lahti L, et al. Fat, fibre and cancer risk in African Americans and rural Africans. Nat Commun. 2015;6:6342. Dietary intervention trial comparing the impact of different diets in African American (high-fat, low-fiber) and rural African (low-fat, high-fiber) people on microbial, metabolic, and mucosal markers associated with CRC risk. A diet switch between both groups demonstrates that changes in microbiota composition and microbial metabolites associated with CRC risk are largely mediated by diet. Critically, this correlates with mucosal markers of proliferation and inflammation in the colon. PubMedPubMedCentralGoogle Scholar
  9. 9.
    Wu GD, Compher C, Chen EZ, et al. Comparative metabolomics in vegans and omnivores reveal constraints on diet-dependent gut microbiota metabolite production. Gut. 2016;65:63–72.PubMedGoogle Scholar
  10. 10.
    • Sonnenburg ED, Smits SA, Tikhonov M, Higginbottom SK, Wingreen NS, Sonnenburg JL. Diet-induced extinctions in the gut microbiota compound over generations. Nature. 2016;529:212–5. Experimental study demonstrating that alterations in murine gut microbiota caused by a diet low in microbiota-accessible carbohydrates (MAC) are reversible within a single generation by reintroduction of MAC, but not after exposing several generations to the low-MAC diet. PubMedPubMedCentralGoogle Scholar
  11. 11.
    Flint HJ, Duncan SH, Louis P. The impact of nutrition on intestinal bacterial communities. Curr Opin Microbiol. 2017;38:59–65.PubMedGoogle Scholar
  12. 12.
    Desai MS, Seekatz AM, Koropatkin NM, et al. A dietary fiber-deprived gut microbiota degrades the colonic mucus barrier and enhances pathogen susceptibility. Cell. 2016;167:1339–1353.e21.PubMedPubMedCentralGoogle Scholar
  13. 13.
    • Schroeder BO, Birchenough GMH, Ståhlman M, Arike L, Johansson MEV, Hansson GC, et al. Bifidobacteria or fiber protects against diet-induced microbiota-mediated colonic mucus deterioration. Cell Host Microbe. 2018;23:27–40.e7. Experimental study demonstrating that changes in gut microbiota composition caused by Western diet promote an impaired mucus barrier function in mice, which is prevented by introduction of Bifidobacterium longum or administration of inulin as source of fiber. PubMedGoogle Scholar
  14. 14.
    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. Scholar
  15. 15.
    Castellarin M, Warren RL, Freeman JD, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012;22:299–306.PubMedPubMedCentralGoogle Scholar
  16. 16.
    Kostic AD, Gevers D, Pedamallu CS, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012;22:292–8.PubMedPubMedCentralGoogle Scholar
  17. 17.
    •• 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. This experimental study uses a gnotobiotic CRC mouse model to demonstrate that the tumorsuppressive effect of dietary fiber is microbiota- and butyrate-dependent. It also shows that butyrate accumulates in tumor colonic epithelial cells acting as histone deacetylase inhibitor, potentially inhibiting colorectal tumorigenesis. PubMedPubMedCentralGoogle Scholar
  18. 18.
    Le Leu RK, Winter JM, Christophersen CT, et al. 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;114:220–30.PubMedPubMedCentralGoogle Scholar
  19. 19.
    Schulz MD, Atay C, Heringer J, et al. High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity. Nature. 2014;514:508–12.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Islam KBMS, Fukiya S, Hagio M, Fujii N, Ishizuka S, Ooka T, et al. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology. 2011;141:1773–81.PubMedGoogle Scholar
  21. 21.
    Cao H, Xu M, Dong W, et al. Secondary bile acid-induced dysbiosis promotes intestinal carcinogenesis. Int J Cancer. 2017. Scholar
  22. 22.
    Ocvirk S, O’Keefe SJ. Influence of bile acids on colorectal cancer risk: potential mechanisms mediated by diet - gut microbiota interactions. Curr Nutr Rep. 2017;6:315–22.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Dermadi D, Valo S, Ollila S, Soliymani R, Sipari N, Pussila M, et al. Western diet deregulates bile acid homeostasis, cell proliferation, and tumorigenesis in colon. Cancer Res. 2017;77:3352–63.PubMedGoogle Scholar
  24. 24.
    • Sheng L, Jena PK, Hu Y, Liu H-X, Nagar N, Kalanetra KM, et al. Hepatic inflammation caused by dysregulated bile acid synthesis is reversible by butyrate supplementation. J Pathol. 2017;243:431–41. Comprehensive experimental study that compares mice lacking the farnesoid X receptor to wild-type mice using Western or control diet. It demonstrates complex interactions of hepatic bile acid metabolism and butyrogenesis in the colon, suggesting an inverse association of hepatic deoxycholic acid and colonic butyrate. PubMedPubMedCentralGoogle Scholar
  25. 25.
    Wirbel J, Pyl PT, Kartal E, et al. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat Med. 2019;25:679.PubMedGoogle Scholar
  26. 26.
    Caesar R, Tremaroli V, Kovatcheva-Datchary P, Cani PD, Bäckhed F. Crosstalk between gut microbiota and dietary lipids aggravates WAT inflammation through TLR signaling. Cell Metab. 2015;22:658–68.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Devkota S, Wang Y, Musch MW, Leone V, Fehlner-Peach H, Nadimpalli A, et al. Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice. Nature. 2012;487:104–8.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Lam YY, Ha CWY, Hoffmann JMA, et al. Effects of dietary fat profile on gut permeability and microbiota and their relationships with metabolic changes in mice. Obesity. 2015;23:1429–39.PubMedGoogle Scholar
  29. 29.
    Yazici C, Wolf PG, Kim H, et al. Race-dependent association of sulfidogenic bacteria with colorectal cancer. Gut. 2017;66:1983–94.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Van Hecke T, Vossen E, Vanden Bussche J, Raes K, Vanhaecke L, De Smet S. Fat content and nitrite-curing influence the formation of oxidation products and NOC-specific DNA adducts during in vitro digestion of meat. PLoS One. 2014;9:e101122.PubMedPubMedCentralGoogle Scholar
  31. 31.
    Beyaz S, Mana MD, Roper J, et al. High-fat diet enhances stemness and tumorigenicity of intestinal progenitors. Nature. 2016;531:53–8.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Jakobsdottir G, Xu J, Molin G, Ahrné S, Nyman M. High-fat diet reduces the formation of butyrate, but increases succinate, inflammation, liver fat and cholesterol in rats, while dietary fibre counteracts these effects. PLoS ONE. 2013;8:e80476.PubMedPubMedCentralGoogle Scholar
  33. 33.
    Wan Y, Wang F, Yuan J, et al. Effects of dietary fat on gut microbiota and faecal metabolites, and their relationship with cardiometabolic risk factors: a 6-month randomised controlled-feeding trial. Gut. 2019. Scholar
  34. 34.
    Reddy BS, Sharma C, Simi B, Engle A, Laakso K, Puska P, et al. Metabolic epidemiology of colon cancer: effect of dietary fiber on fecal mutagens and bile acids in healthy subjects. Cancer Res. 1987;47:644–8.PubMedGoogle Scholar
  35. 35.
    Reddy B, Engle A, Katsifis S, Simi B, Bartram HP, Perrino P, et al. Biochemical epidemiology of colon cancer: effect of types of dietary fiber on fecal mutagens, acid, and neutral sterols in healthy subjects. Cancer Res. 1989;49:4629–35.PubMedGoogle Scholar
  36. 36.
    Bartram HP, Englert S, Scheppach W, Dusel G, Richter F, Richter A, et al. Antagonistic effects of deoxycholic acid and butyrate on epithelial cell proliferation in the proximal and distal human colon. Z Gastroenterol. 1994;32:389–92.PubMedGoogle Scholar
  37. 37.
    McMillan L, Butcher S, Wallis Y, Neoptolemos JP, Lord JM. Bile acids reduce the apoptosis-inducing effects of sodium butyrate on human colon adenoma (AA/C1) cells: implications for colon carcinogenesis. Biochem Biophys Res Commun. 2000;273:45–9.PubMedGoogle Scholar
  38. 38.
    Rosignoli P, Fabiani R, De Bartolomeo A, Fuccelli R, Pelli MA, Morozzi G. Genotoxic effect of bile acids on human normal and tumour colon cells and protection by dietary antioxidants and butyrate. Eur J Nutr. 2008;47:301–9.PubMedGoogle Scholar
  39. 39.
    Zeng H, Claycombe KJ, Reindl KM. Butyrate and deoxycholic acid play common and distinct roles in HCT116 human colon cell proliferation. J Nutr Biochem. 2015;26:1022–8.PubMedGoogle Scholar
  40. 40.
    Perdue DG, Haverkamp D, Perkins C, Daley CM, Provost E. Geographic variation in colorectal cancer incidence and mortality, age of onset, and stage at diagnosis among American Indian and Alaska Native people, 1990-2009. Am J Public Health. 2014;104(Suppl 3):S404–14.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Gill CIR, Heavey P, McConville E, Bradbury I, Fässler C, Mueller S, et al. Effect of fecal water on an in vitro model of colonic mucosal barrier function. Nutr Cancer. 2007;57:59–65.PubMedGoogle Scholar
  42. 42.
    Windey K, De Preter V, Huys G, Broekaert WF, Delcour JA, Louat T, et al. Wheat bran extract alters colonic fermentation and microbial composition, but does not affect faecal water toxicity: a randomised controlled trial in healthy subjects. Br J Nutr. 2015;113:225–38.PubMedGoogle Scholar
  43. 43.
    Ou J, Carbonero F, Zoetendal EG, DeLany JP, Wang M, Newton K, 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.PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Soeren Ocvirk
    • 1
    • 2
  • Annette S. Wilson
    • 1
  • Corynn N. Appolonia
    • 1
  • Timothy K. Thomas
    • 3
  • Stephen J. D. O’Keefe
    • 1
    Email author
  1. 1.Division of Gastroenterology, Hepatology and Nutrition, Department of MedicineUniversity of PittsburghPittsburghUSA
  2. 2.Department of Gastrointestinal MicrobiologyGerman Institute of Human Nutrition Potsdam-RehbrueckeNuthetalGermany
  3. 3.Clinical & Research Services, Community Health ServicesAlaska Native Tribal Health ConsortiumAnchorageUSA

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