Skip to main content

Advertisement

SpringerLink
Log in

Diet and Gut Microbes Act Coordinately to Enhance Programmed Cell Death and Reduce Colorectal Cancer Risk

  • Review
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Diet is an important risk factor for colorectal cancer (CRC), and several dietary constituents implicated in CRC are modified by gut microbial metabolism. Microbial fermentation of dietary fiber produces short-chain fatty acids, e.g., acetate, propionate, and butyrate. Dietary fiber has been shown to reduce colon tumors in animal models, and, in vitro, butyrate influences cellular pathways important to cancer risk. Furthermore, work from our group suggests that the combined effects of butyrate and omega-3 polyunsaturated fatty acids (n-3 PUFA) may enhance the chemopreventive potential of these dietary constituents. We postulate that the relatively low intakes of n-3 PUFA and fiber in Western populations and the failure to address interactions between these dietary components may explain why chemoprotective effects of n-3 PUFA and fermentable fibers have not been detected consistently in prospective cohort studies. In this review, we summarize the evidence outlining the effects of n-3 long-chain PUFA and highly fermentable fiber with respect to alterations in critical pathways important to CRC prevention, particularly intrinsic mitochondrial-mediated programmed cell death resulting from the accumulation of lipid reactive oxygen species (ferroptosis), and epigenetic programming related to lipid catabolism and beta-oxidation-associated genes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Trock B, Lanza E, Greenwald P. Dietary fiber, vegetables, and colon cancer: critical review and meta-analyses of the epidemiologic evidence. Natl Cancer Inst. 2018;1990:650–661.

    Google Scholar 

  2. Ben Q, Sun Y, Chai R, Qian A, Xu B, Yuan Y. Dietary fiber intake reduces risk for colorectal adenoma: a meta-analysis. Gastroenterology. 2014;146(689–699):e686.

    Google Scholar 

  3. Perez-Cueto FJ, Verbeke W. Consumer implications of the WCRF’s permanent update on colorectal cancer. Meat Sci. 2012;90:977–978.

    Article  PubMed  Google Scholar 

  4. Research WC. Diet, nutrition, physical activity and colorectal cancer. City. 2018. http://www.aicr.org/continuous-update-project/colorectal-cancer.html.

  5. Schatzkin A, Mouw T, Park Y, et al. Dietary fiber and whole-grain consumption in relation to colorectal cancer in the NIH-AARP Diet and Health Study. Am J Clin Nutr. 2007;85:1353–1360.

    Article  CAS  PubMed  Google Scholar 

  6. Murphy N, Norat T, Ferrari P, et al. Dietary fibre intake and risks of cancers of the colon and rectum in the European prospective investigation into cancer and nutrition (EPIC). PLoS One. 2012;7:e39361.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Aune D, Chan DS, Lau R, et al. Dietary fibre, whole grains, and risk of colorectal cancer: systematic review and dose-response meta-analysis of prospective studies. BMJ. 2011;343:d6617.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Navarro SL, Neuhouser ML, Cheng TD, et al. The interaction between dietary fiber and fat and risk of colorectal cancer in the women’s health initiative. Nutrients. 2016;8:779.

    Article  PubMed Central  CAS  Google Scholar 

  9. Thompson HJ, Brick MA. Perspective: closing the dietary fiber gap: an ancient solution for a 21st century problem. Adv Nutr. 2016;7:623–626.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Bingham SA. Diet and large bowel cancer. J R Soc Med. 1990;83:420–422.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Young GP, Hu Y, Le Leu RK, Nyskohus L. Dietary fibre and colorectal cancer: a model for environment–gene interactions. Mol Nutr Food Res. 2005;49:571–584.

    Article  PubMed  Google Scholar 

  12. Slavin JL. Dietary fiber and body weight. Nutrition. 2005;21:411–418.

    Article  PubMed  Google Scholar 

  13. Chen T, Long W, Zhang C, Liu S, Zhao L, Hamaker BR. Fiber-utilizing capacity varies in Prevotella- versus Bacteroides-dominated gut microbiota. Sci Rep. 2017;7:2594.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Donohoe DR, Bultman SJ. Metaboloepigenetics: interrelationships between energy metabolism and epigenetic control of gene expression. J Cell Physiol. 2012;227:3169–3177.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Donohoe DR, Garge N, Zhang X, et al. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab. 2011;13:517–526.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Wang T, Cai G, Qiu Y, et al. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J. 2012;6:320–329.

    Article  CAS  PubMed  Google Scholar 

  17. Wu N, Yang X, Zhang R, et al. Dysbiosis signature of fecal microbiota in colorectal cancer patients. Microb Ecol. 2013;66:462–470.

    Article  CAS  PubMed  Google Scholar 

  18. Weir TL, Manter DK, Sheflin AM, Barnett BA, Heuberger AL, Ryan EP. Stool microbiome and metabolome differences between colorectal cancer patients and healthy adults. PLoS One. 2013;8:e70803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Patnode ML, Beller ZW, Han ND, et al. Interspecies competition impacts targeted manipulation of human gut bacteria by fiber-derived. Glycans Cell. 2019;179(59–73):e13.

    Google Scholar 

  20. Makki K, Deehan EC, Walter J, Backhed F. The impact of dietary fiber on gut microbiota in host health and disease. Cell Host Microbe. 2018;23:705–715.

    Article  CAS  PubMed  Google Scholar 

  21. Duncan SH, Holtrop G, Lobley GE, Calder AG, Stewart CS, Flint HJ. Contribution of acetate to butyrate formation by human faecal bacteria. Br J Nutr. 2004;91:915–923.

    Article  CAS  PubMed  Google Scholar 

  22. Uchida K, Kono S, Yin G, et al. Dietary fiber, source foods and colorectal cancer risk: the Fukuoka Colorectal Cancer Study. Scand J Gastroenterol. 2010;45:1223–1231.

    Article  CAS  PubMed  Google Scholar 

  23. Wakai K, Date C, Fukui M, et al. Dietary fiber and risk of colorectal cancer in the Japan collaborative cohort study. Cancer Epidemiol Biomarkers Prev. 2007;16:668–675.

    Article  CAS  PubMed  Google Scholar 

  24. Levi F, Pasche C, Lucchini F, La Vecchia C. Dietary fibre and the risk of colorectal cancer. Eur J Cancer. 2001;37:2091–2096.

    Article  CAS  PubMed  Google Scholar 

  25. Freudenheim JL, Graham S, Horvath PJ, Marshall JR, Haughey BP, Wilkinson G. Risks associated with source of fiber and fiber components in cancer of the colon and rectum. Cancer Res. 1990;50:3295–3300.

    CAS  PubMed  Google Scholar 

  26. Le Marchand L, Hankin JH, Wilkens LR, Kolonel LN, Englyst HN, Lyu LC. Dietary fiber and colorectal cancer risk. Epidemiology. 1997;8:658–665.

    Article  PubMed  Google Scholar 

  27. Negri E, Franceschi S, Parpinel M, La Vecchia C. Fiber intake and risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev.. 1998;7:667–671.

    CAS  PubMed  Google Scholar 

  28. Sellem L, Srour B, Gueraud F, et al. Saturated, mono- and polyunsaturated fatty acid intake and cancer risk: results from the French prospective cohort. NutriNet-Sante Eur J Nutr.. 2019;58:1515–1527.

    Article  CAS  PubMed  Google Scholar 

  29. Strobel C, Jahreis G, Kuhnt K. Survey of n-3 and n-6 polyunsaturated fatty acids in fish and fish products. Lipids Health Dis. 2012;11:144.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Simopoulos AP. Importance of the omega-6/omega-3 balance in health and disease: evolutionary aspects of diet. World Rev Nutr Diet. 2011;102:10–21.

    Article  CAS  PubMed  Google Scholar 

  31. Skender B, Vaculova AH, Hofmanova J. Docosahexaenoic fatty acid (DHA) in the regulation of colon cell growth and cell death: a review. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub.. 2012;156:186–199.

    Article  CAS  PubMed  Google Scholar 

  32. Azer SS. Overview of molecular pathways in inflammatory bowel disease associated with colorectal cancer development. Eur J Gastroenterol Hepatol.. 2012;25:271–281.

    Article  CAS  Google Scholar 

  33. Cockbain AJ, Toogood GJ, Hull MA. Omega-3 polyunsaturated fatty acids for the treatment and prevention of colorectal cancer. Gut. 2012;61:135–149.

    Article  CAS  PubMed  Google Scholar 

  34. Chang WC, Chapkin RS, Lupton JR. Predictive value of proliferation, differentiation and apoptosis as intermediate markers for colon tumorigenesis. Carcinogenesis. 1997;18:721–730.

    Article  CAS  PubMed  Google Scholar 

  35. Hou TY, Davidson LA, Kim E, et al. Nutrient-gene interaction in colon cancer, from the membrane to cellular physiology. Annu Rev Nutr. 2016;36:543–570.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Reddy BS. Omega-3 fatty acids in colorectal cancer prevention. Int J Cancer. 2004;112:1–7.

    Article  CAS  PubMed  Google Scholar 

  37. Fuentes NR, Mlih M, Barhoumi R, et al. Long-chain n-3 fatty acids attenuate oncogenic KRas-driven proliferation by altering plasma membrane nanoscale proteolipid composition. Cancer Res. 2018;78:3899–3912.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wu S, Feng B, Li K, et al. Fish consumption and colorectal cancer risk in humans: a systematic review and meta-analysis. Am J Med.. 2012;125(551–559):e555.

    Google Scholar 

  39. Geelen A, Schouten JM, Kamphuis C, et al. Fish consumption, n-3 fatty acids, and colorectal cancer: a meta-analysis of prospective cohort studies. Am J Epidemiol. 2007;166:1116–1125.

    Article  PubMed  Google Scholar 

  40. MacLean CH, Newberry SJ, Mojica WA, et al. Effects of omega-3 fatty acids on cancer risk: a systematic review. JAMA. 2006;295:403–415.

    Article  CAS  PubMed  Google Scholar 

  41. Gerber M. Omega-3 fatty acids and cancers: a systematic update review of epidemiological studies. Br J Nutr. 2012;107:S228–S239.

    Article  CAS  PubMed  Google Scholar 

  42. Song M, Chan AT, Fuchs CS, et al. Dietary intake of fish, omega-3 and omega-6 fatty acids and risk of colorectal cancer: a prospective study in U.S. men and women. Int J Cancer. 2014;135:2413–2423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. 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;2:1197–1206.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Kantor ED, Lampe JW, Peters U, Vaughan TL, White E. Long-chain omega-3 polyunsaturated fatty acid intake and risk of colorectal cancer. Nutr Cancer.. 2014;66:716–727.

    Article  CAS  PubMed  Google Scholar 

  45. Van Blarigan EL, Fuchs CS, Niedzwiecki D, et al. Marine omega-3 polyunsaturated fatty acid and fish intake after colon cancer diagnosis and survival: CALGB 89803 (alliance). Cancer Epidemiol Biomarkers Prev. 2018;27:438–445.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Chapkin RS, Fan Y, Lupton JR. Effect of diet on colonic-programmed cell death: molecular mechanism of action. Toxicol Lett.. 2000;112–113:411–414.

    Article  PubMed  Google Scholar 

  47. Cho Y, Turner ND, Davidson LA, Chapkin RS, Carroll RJ, Lupton JR. Colon cancer cell apoptosis is induced by combined exposure to the n-3 fatty acid docosahexaenoic acid and butyrate through promoter methylation. Exp Biol Med (Maywood). 2014;239:302–310.

    Article  CAS  Google Scholar 

  48. Kolar S, Barhoumi R, Jones CK, et al. Interactive effects of fatty acid and butyrate-induced mitochondrial Ca(2)(+) loading and apoptosis in colonocytes. Cancer. 2011;117:5294–5303.

    Article  CAS  PubMed  Google Scholar 

  49. Kansal S, Negi AK, Bhatnagar A, Agnihotri N. Ras signaling pathway in the chemopreventive action of different ratios of fish oil and corn oil in experimentally induced colon carcinogenesis. Nutr Cancer.. 2012;64:559–568.

    Article  CAS  PubMed  Google Scholar 

  50. Sarotra P, Kansal S, Sandhir R, Agnihotri N. Chemopreventive effect of different ratios of fish oil and corn oil on prognostic markers, DNA damage and cell cycle in colon carcinogenesis. Eur J Cancer Prev. 2012;21:147–154.

    Article  CAS  PubMed  Google Scholar 

  51. Kolar SS, Barhoumi R, Callaway ES, et al. Synergy between docosahexaenoic acid and butyrate elicits p53-independent apoptosis via mitochondrial Ca(2 +) accumulation in colonocytes. Am J Physiol Gastrointest Liver Physiol.. 2007;293:G935–G943.

    Article  CAS  PubMed  Google Scholar 

  52. Orlich MJ, Singh PN, Sabate J, et al. Vegetarian dietary patterns and the risk of colorectal cancers. JAMA Intern Med.. 2015;175:767–776.

    Article  PubMed  PubMed Central  Google Scholar 

  53. 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.

    Article  PubMed  CAS  Google Scholar 

  54. Kraja B, Muka T, Ruiter R, et al. Dietary fiber intake modifies the positive association between n-3 PUFA intake and colorectal cancer risk in a caucasian population. J Nutr.. 2015;145:1709–1716.

    Article  CAS  PubMed  Google Scholar 

  55. Sanders LM, Henderson CE, Hong MY, et al. An increase in reactive oxygen species by dietary fish oil coupled with the attenuation of antioxidant defenses by dietary pectin enhances rat colonocyte apoptosis. J Nutr. 2004;134:3233–3238.

    Article  CAS  PubMed  Google Scholar 

  56. Vanamala J, Glagolenko A, Yang P, et al. Dietary fish oil and pectin enhance colonocyte apoptosis in part through suppression of PPARdelta/PGE2 and elevation of PGE3. Carcinogenesis. 2008;29:790–796.

    Article  CAS  PubMed  Google Scholar 

  57. Crim KC, Sanders LM, Hong MY, et al. Upregulation of p21Waf1/Cip1 expression in vivo by butyrate administration can be chemoprotective or chemopromotive depending on the lipid component of the diet. Carcinogenesis. 2008;29:1415–1420.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Cho Y, Kim H, Turner ND, et al. A chemoprotective fish oil- and pectin-containing diet temporally alters gene expression profiles in exfoliated rat colonocytes throughout oncogenesis. J Nutr. 2011;141:1029–1035.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Chapkin RS, DeClercq V, Kim E, Fuentes NR, Fan YY. Mechanisms by Which Pleiotropic Amphiphilic n-3 PUFA Reduce Colon Cancer Risk. Curr Colorectal Cancer Rep. 2014;10:442–452.

    Article  PubMed  PubMed Central  Google Scholar 

  60. Triff K, Kim E, Chapkin RS. Chemoprotective epigenetic mechanisms in a colorectal cancer model: Modulation by n-3 PUFA in combination with fermentable fiber. Curr Pharmacol Rep. 2015;1:11–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kolar SS, Barhoumi R, Lupton JR, Chapkin RS. Docosahexaenoic acid and butyrate synergistically induce colonocyte apoptosis by enhancing mitochondrial Ca2 + accumulation. Cancer Res. 2007;67:5561–5568.

    Article  CAS  PubMed  Google Scholar 

  62. Jiang YH, Lupton JR, Chapkin RS. Dietary fat and fiber modulate the effect of carcinogen on colonic protein kinase C lambda expression in rats. J Nutr.. 1997;127:1938–1943.

    Article  CAS  PubMed  Google Scholar 

  63. Triff K, McLean MW, Callaway E, Goldsby J, Ivanov I, Chapkin RS. Dietary fat and fiber interact to uniquely modify global histone post-translational epigenetic programming in a rat colon cancer progression model. Int J Cancer. 2018;143:1402–1415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Zimmerman MA, Singh N, Martin PM, et al. Butyrate suppresses colonic inflammation through HDAC1-dependent Fas upregulation and Fas-mediated apoptosis of T cells. Am J Physiol Gastrointest Liver Physiol. 2012;302:G1405–G1415.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Donohoe DR, Collins LB, Wali A, Bigler R, Sun W, Bultman SJ. The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol Cell.. 2012;48:612–626.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Bultman SJ. Molecular pathways: gene-environment interactions regulating dietary fiber induction of proliferation and apoptosis via butyrate for cancer prevention. Clin Cancer Res. 2014;20:799–803.

    Article  CAS  PubMed  Google Scholar 

  67. Roediger WE. Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology. 1982;83:424–429.

    Article  CAS  PubMed  Google Scholar 

  68. Ng Y, Barhoumi R, Tjalkens RB, et al. The role of docosahexaenoic acid in mediating mitochondrial membrane lipid oxidation and apoptosis in colonocytes. Carcinogenesis. 2005;26:1914–1921.

    Article  CAS  PubMed  Google Scholar 

  69. Fan YY, Zhan Y, Aukema HM, et al. Proapoptotic effects of dietary (n-3) fatty acids are enhanced in colonocytes of manganese-dependent superoxide dismutase knockout mice. J Nutr. 2009;139:1328–1332.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Fan YY, Ran Q, Toyokuni S, et al. Dietary fish oil promotes colonic apoptosis and mitochondrial proton leak in oxidatively stressed mice. Cancer Prev Res (Phila).. 2011;4:1267–1274.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Kelso GF, Porteous CM, Coulter CV, et al. Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. J Biol Chem.. 2001;276:4588–4596.

    Article  CAS  PubMed  Google Scholar 

  72. Lyn PC, Lim TH. Listeria meningitis resistant to ampicillin. J Singapore Paediatr Soc.. 1986;28:247–249.

    CAS  PubMed  Google Scholar 

  73. Stockwell BR, Friedmann Angeli JP, Bayir H, et al. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell. 2017;171:273–285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Orrenius S, Zhivotovsky B, Nicotera P. Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol. 2003;4:552–565.

    Article  CAS  PubMed  Google Scholar 

  75. Bedi A, Pasricha PJ, Akhtar AJ, et al. Inhibition of apoptosis during development of colorectal cancer. Cancer Res. 1995;55:1811–1816.

    CAS  PubMed  Google Scholar 

  76. Shah MS, Kim E, Davidson LA, et al. Comparative effects of diet and carcinogen on microRNA expression in the stem cell niche of the mouse colonic crypt. Biochim Biophys Acta. 1862;2016:121–134.

    Google Scholar 

  77. Litvak Y, Byndloss MX, Tsolis RM, Baumler AJ. Dysbiotic proteobacteria expansion: a microbial signature of epithelial dysfunction. Curr Opin Microbiol. 2017;39:1–6.

    Article  CAS  PubMed  Google Scholar 

  78. Litvak Y, Byndloss MX, Baumler AJ. Colonocyte metabolism shapes the gut microbiota. Science. 2018;362:eaat9076.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Kelly CJ, Zheng L, Campbell EL, et al. Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function. Cell Host Microbe. 2015;17:662–671.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Lampe JW, Kim E, Levy L, et al. Colonic mucosal and exfoliome transcriptomic profiling and fecal microbiome response to a flaxseed lignan extract intervention in humans. Am J Clin Nutr. 2019;110:377–390.

    Article  PubMed  PubMed Central  Google Scholar 

  82. David LA, Maurice CF, Carmody RN, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505:559–563.

    Article  CAS  PubMed  Google Scholar 

  83. Hooda S, Boler BM, Serao MC, et al. 454 pyrosequencing reveals a shift in fecal microbiota of healthy adult men consuming polydextrose or soluble corn fiber. J Nutr.. 2012;142:1259–1265.

    Article  CAS  PubMed  Google Scholar 

  84. Ross AB, Bruce SJ, Blondel-Lubrano A, et al. A whole-grain cereal-rich diet increases plasma betaine, and tends to decrease total and LDL-cholesterol compared with a refined-grain diet in healthy subjects. Br J Nutr. 2011;105:1492–1502.

    Article  CAS  PubMed  Google Scholar 

  85. Costabile A, Klinder A, Fava F, et al. Whole-grain wheat breakfast cereal has a prebiotic effect on the human gut microbiota: a double-blind, placebo-controlled, crossover study. Br J Nutr. 2008;99:110–120.

    Article  CAS  PubMed  Google Scholar 

  86. Finley JW, Burrell JB, Reeves PG. Pinto bean consumption changes SCFA profiles in fecal fermentations, bacterial populations of the lower bowel, and lipid profiles in blood of humans. J Nutr. 2007;137:2391–2398.

    Article  CAS  PubMed  Google Scholar 

  87. Smith SC, Choy R, Johnson SK, Hall RS, Wildeboer-Veloo AC, Welling GW. Lupin kernel fiber consumption modifies fecal microbiota in healthy men as determined by rRNA gene fluorescent in situ hybridization. Eur J Nutr. 2006;45:335–341.

    Article  CAS  PubMed  Google Scholar 

  88. Johnson SK, Chua V, Hall RS, Baxter AL. Lupin kernel fibre foods improve bowel function and beneficially modify some putative faecal risk factors for colon cancer in men. Br J Nutr. 2006;95:372–378.

    Article  CAS  PubMed  Google Scholar 

  89. Tuohy KM, Kolida S, Lustenberger AM, Gibson GR. The prebiotic effects of biscuits containing partially hydrolysed guar gum and fructo-oligosaccharides–a human volunteer study. Br J Nutr.. 2001;86:341–348.

    Article  CAS  PubMed  Google Scholar 

  90. Hylla S, Gostner A, Dusel G, et al. Effects of resistant starch on the colon in healthy volunteers: possible implications for cancer prevention. Am J Clin Nutr. 1998;67:136–142.

    Article  CAS  PubMed  Google Scholar 

  91. Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature. 2011;473:174–180.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Faust K, Raes J. Microbial interactions: from networks to models. Nat Rev Microbiol. 2012;10:538–550.

    Article  CAS  PubMed  Google Scholar 

  93. Faust K, Sathirapongsasuti JF, Izard J, et al. Microbial co-occurrence relationships in the human microbiome. PLoS Comput Biol. 2012;8:e1002606.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Lozupone C, Faust K, Raes J, et al. Identifying genomic and metabolic features that can underlie early successional and opportunistic lifestyles of human gut symbionts. Genome Res. 2012;22:1974–1984.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Bolca S, Van de Wiele T, Possemiers S. Gut metabotypes govern health effects of dietary polyphenols. Curr Opin Biotechnol. 2013;24:220–225.

    Article  CAS  PubMed  Google Scholar 

  96. Heinzmann SS, Merrifield CA, Rezzi S, et al. Stability and robustness of human metabolic phenotypes in response to sequential food challenges. J Proteome Res. 2012;11:643–655.

    Article  CAS  PubMed  Google Scholar 

  97. Walker AW, Ince J, Duncan SH, et al. Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME J. 2011;5:220–230.

    Article  CAS  PubMed  Google Scholar 

  98. Weickert MO, Arafat AM, Blaut M, et al. Changes in dominant groups of the gut microbiota do not explain cereal-fiber induced improvement of whole-body insulin sensitivity. Nutr Metab (Lond). 2011;8:90.

    Article  CAS  Google Scholar 

  99. Russell WR, Gratz SW, Duncan SH, et al. High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health. Am J Clin Nutr.. 2011;93:1062–1072.

    Article  CAS  PubMed  Google Scholar 

  100. Duncan SH, Belenguer A, Holtrop G, Johnstone AM, Flint HJ, Lobley GE. Reduced dietary intake of carbohydrates by obese subjects results in decreased concentrations of butyrate and butyrate-producing bacteria in feces. Appl Environ Microbiol. 2007;73:1073–1078.

    Article  CAS  PubMed  Google Scholar 

  101. Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: human gut microbes associated with obesity. Nature.. 2006;444:1022–1023.

    Article  CAS  PubMed  Google Scholar 

  102. Cummings JH, Pomare EW, Branch WJ, Naylor CP, Macfarlane GT. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut. 1987;28:1221–1227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Louis P, McCrae SI, Charrier C, Flint HJ. Organization of butyrate synthetic genes in human colonic bacteria: phylogenetic conservation and horizontal gene transfer. FEMS Microbiol Lett.. 2007;269:240–247.

    Article  CAS  PubMed  Google Scholar 

  104. Louis P, Scott KP, Duncan SH, Flint HJ. Understanding the effects of diet on bacterial metabolism in the large intestine. J Appl Microbiol. 2007;102:1197–1208.

    Article  CAS  PubMed  Google Scholar 

  105. Ley RE, Lozupone CA, Hamady M, Knight R, Gordon JI. Worlds within worlds: evolution of the vertebrate gut microbiota. Nat Rev Microbiol. 2008;6:776–788.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Gibson GR, Macfarlane GT, Cummings JH. Sulphate reducing bacteria and hydrogen metabolism in the human large intestine. Gut. 1993;34:437–439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Vital M, Howe AC, Tiedje JM. Revealing the bacterial butyrate synthesis pathways by analyzing (meta)genomic data. MBio. 2014;5:e00889.

    Article  PubMed  PubMed Central  Google Scholar 

  108. Barcenilla A, Pryde SE, Martin JC, et al. Phylogenetic relationships of butyrate-producing bacteria from the human gut. Appl Environ Microbiol. 2000;66:1654–1661.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Matthies C, Schink B. Fermentative degradation of glutarate via decarboxylation by newly isolated strictly anaerobic bacteria. Arch Microbiol. 1992;157:290–296.

    Article  CAS  PubMed  Google Scholar 

  110. Matthies C, Schink B. Reciprocal isomerization of butyrate and isobutyrate by the strictly anaerobic bacterium strain WoG13 and methanogenic isobutyrate degradation by a defined triculture. Appl Environ Microbiol.. 1992;58:1435–1439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Roeder J, Schink B. Syntrophic degradation of cadaverine by a defined methanogenic coculture. Appl Environ Microbiol. 2009;75:4821–4828.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Gharbia SE, Shah HN. Pathways of glutamate catabolism among Fusobacterium species. J Gen Microbiol. 1991;137:1201–1206.

    Article  CAS  PubMed  Google Scholar 

  113. Gerhardt A, Cinkaya I, Linder D, Huisman G, Buckel W. Fermentation of 4-aminobutyrate by Clostridium aminobutyricum: cloning of two genes involved in the formation and dehydration of 4-hydroxybutyryl-CoA. Arch Microbiol.. 2000;174:189–199.

    Article  CAS  PubMed  Google Scholar 

  114. Buckel W. Unusual enzymes involved in five pathways of glutamate fermentation. Appl Microbiol Biotechnol. 2001;57:263–273.

    Article  CAS  PubMed  Google Scholar 

  115. Kreimeyer A, Perret A, Lechaplais C, et al. Identification of the last unknown genes in the fermentation pathway of lysine. J Biol Chem. 2007;282:7191–7197.

    Article  CAS  PubMed  Google Scholar 

  116. Potrykus J, White RL, Bearne SL. Proteomic investigation of amino acid catabolism in the indigenous gut anaerobe Fusobacterium varium. Proteomics. 2008;8:2691–2703.

    Article  CAS  PubMed  Google Scholar 

  117. Uematsu H, Hoshino E. Degradation of arginine and other amino acids by Eubacterium nodatum ATCC 33099. Microb Ecol Health Dis.. 1996;9:305–311.

    Article  Google Scholar 

  118. Hippe B, Zwielehner J, Liszt K, Lassl C, Unger F, Haslberger AG. Quantification of butyryl CoA:acetate CoA-transferase genes reveals different butyrate production capacity in individuals according to diet and age. FEMS Microbiol Lett. 2011;316:130–135.

    Article  CAS  PubMed  Google Scholar 

  119. Louis P, Young P, Holtrop G, Flint HJ. Diversity of human colonic butyrate-producing bacteria revealed by analysis of the butyryl-CoA:acetate CoA-transferase gene. Environ Microbiol.. 2010;12:304–314.

    Article  CAS  PubMed  Google Scholar 

  120. Louis P, Flint HJ. Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiol Lett. 2009;294:1–8.

    Article  CAS  PubMed  Google Scholar 

  121. Duncan SH, Barcenilla A, Ste wart CS, Pryde SE, Flint HJ. Acetate utilization and butyryl coenzyme A, :acetate-CoA transferase in butyrate-producing bacteria from the human large intestine. Appl Environ Microbiol.. 2002;68:5186–5190.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Vital M, Gao J, Rizzo M, Harrison T, Tiedje JM. Diet is a major factor governing the fecal butyrate-producing community structure across mammalia, aves and reptilia. ISME J.. 2015;9:832–843.

    Article  CAS  PubMed  Google Scholar 

  123. Fernandes J, Wang A, Su W, et al. Age, dietary fiber, breath methane, and fecal short chain fatty acids are interrelated in Archaea-positive humans. J Nutr. 2013;143:1269–1275.

    Article  CAS  PubMed  Google Scholar 

  124. Guy CJ. Abell MACALM. Methanogenic archaea in adult human faecal samples are inversely related to butyrate concentration. Microb Ecol Health Dis. 2006;18:154–160.

    Google Scholar 

  125. Ragsdale SW, Pierce E. Acetogenesis and the Wood-Ljungdahl pathway of CO(2) fixation. Biochim Biophys Acta.. 2008;1784:1873–1898.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Cheng J, Ogawa K, Kuriki K, et al. Increased intake of n-3 polyunsaturated fatty acids elevates the level of apoptosis in the normal sigmoid colon of patients polypectomized for adenomas/tumors. Cancer Lett.. 2003;193:17–24.

    Article  CAS  PubMed  Google Scholar 

  127. Courtney ED, Matthews S, Finlayson C, et al. Eicosapentaenoic acid (EPA) reduces crypt cell proliferation and increases apoptosis in normal colonic mucosa in subjects with a history of colorectal adenomas. Int J Colorectal Dis.. 2007;22:765–776.

    Article  CAS  PubMed  Google Scholar 

  128. Lochhead P, Chan AT, Nishihara R, et al. Etiologic field effect: reappraisal of the field effect concept in cancer predisposition and progression. Mod Pathol. 2015;28:14–29.

    Article  PubMed  Google Scholar 

  129. Wu GD, Chen J, Hoffmann C, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011;334:105–108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Tilg H, Kaser A. Gut microbiome, obesity, and metabolic dysfunction. J Clin Invest.. 2011;121:2126–2132.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Ley RE. Obesity and the human microbiome. Curr Opin Gastroenterol. 2010;26:5–11.

    Article  PubMed  Google Scholar 

  132. O’Keefe SJ. Nutrition and colonic health: the critical role of the microbiota. Curr Opin Gastroenterol. 2008;24:51–58.

    Article  PubMed  Google Scholar 

  133. Patterson E, O’Doherty RM, Murphy EF, et al. Impact of dietary fatty acids on metabolic activity and host intestinal microbiota composition in C57BL/6 J mice. Br J Nutr.. 2014;111:1905–1917.

    Article  CAS  PubMed  Google Scholar 

  134. Tabbaa M, Golubic M, Roizen MF, Bernstein AM. Docosahexaenoic acid, inflammation, and bacterial dysbiosis in relation to periodontal disease, inflammatory bowel disease, and the metabolic syndrome. Nutrients. 2013;5:3299–3310.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Urwin HJ, Miles EA, Noakes PS, et al. Effect of salmon consumption during pregnancy on maternal and infant faecal microbiota, secretory IgA and calprotectin. Br J Nutr. 2014;111:773–784.

    Article  CAS  PubMed  Google Scholar 

  136. Geier MS, Torok VA, Allison GE, et al. Dietary omega-3 polyunsaturated fatty acid does not influence the intestinal microbial communities of broiler chickens. Poult Sci.. 2009;88:2399–2405.

    Article  CAS  PubMed  Google Scholar 

  137. Yu HN, Zhu J, Pan WS, Shen SR, Shan WG, Das UN. Effects of fish oil with a high content of n-3 polyunsaturated fatty acids on mouse gut microbiota. Arch Med Res.. 2014;45:195–202.

    Article  CAS  PubMed  Google Scholar 

  138. Sun M, Zhou Z, Dong J, Zhang J, Xia Y, Shu R. Antibacterial and antibiofilm activities of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) against periodontopathic bacteria. Microb Pathog.. 2016;99:196–203.

    Article  CAS  PubMed  Google Scholar 

  139. Rodes L, Khan A, Paul A, et al. Effect of probiotics Lactobacillus and Bifidobacterium on gut-derived lipopolysaccharides and inflammatory cytokines: an in vitro study using a human colonic microbiota model. J Microbiol Biotechnol. 2013;23:518–526.

    Article  CAS  PubMed  Google Scholar 

  140. Elmadfa I, Klein P, Meyer AL. Immune-stimulating effects of lactic acid bacteria in vivo and in vitro. Proc Nutr Soc. 2010;69:416–420.

    Article  CAS  PubMed  Google Scholar 

  141. Cani PD, Bibiloni R, Knauf C, et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes. 2008;57:1470–1481.

    Article  CAS  PubMed  Google Scholar 

  142. Karlsson H, Larsson P, Wold AE, Rudin A. Pattern of cytokine responses to gram-positive and gram-negative commensal bacteria is profoundly changed when monocytes differentiate into dendritic cells. Infect Immun. 2004;72:2671–2678.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Desbois AP, Smith VJ. Antibacterial free fatty acids: activities, mechanisms of action and biotechnological potential. Appl Microbiol Biotechnol.. 2010;85:1629–1642.

    Article  CAS  PubMed  Google Scholar 

  144. Mima K, Cao Y, Chan AT, et al. Fusobacterium nucleatum in colorectal carcinoma tissue according to tumor location. Clin Transl Gastroenterol. 2016;7:e200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. 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;3:921–927.

    Article  PubMed  PubMed Central  Google Scholar 

  146. Barone M, Notarnicola M, Caruso MG, et al. Olive oil and omega-3 polyunsaturated fatty acids suppress intestinal polyp growth by modulating the apoptotic process in ApcMin/+ mice. Carcinogenesis. 2014;35:1613–1619.

    Article  CAS  PubMed  Google Scholar 

  147. 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. Int J Cancer.. 2014;135:2004–2013.

    Article  CAS  PubMed  Google Scholar 

  148. Han YM, Park JM, Cha JY, Jeong M, Go EJ, Hahm KB. Endogenous conversion of omega-6 to omega-3 polyunsaturated fatty acids in fat-1 mice attenuated intestinal polyposis by either inhibiting COX-2/beta-catenin signaling or activating 15-PGDH/IL-18. Int J Cancer.. 2016;138:2247–2256.

    Article  CAS  PubMed  Google Scholar 

  149. Pot GK, Geelen A, van Heijningen EM, Siezen CL, van Kranen HJ, Kampman E. Opposing associations of serum n-3 and n-6 polyunsaturated fatty acids with colorectal adenoma risk: an endoscopy-based case-control study. Int J Cancer.. 2008;123:1974–1977.

    Article  CAS  PubMed  Google Scholar 

  150. Goncalves P, Martel F. Butyrate and colorectal cancer: the role of butyrate transport. Curr Drug Metab.. 2013;14:994–1008.

    Article  CAS  PubMed  Google Scholar 

  151. Sengupta S, Tjandra JJ, Gibson PR. Dietary fiber and colorectal neoplasia. Dis Colon Rectum. 2001;44:1016–1033.

    Article  CAS  PubMed  Google Scholar 

  152. McIntyre A, Gibson PR, Young GP. Butyrate production from dietary fibre and protection against large bowel cancer in a rat model. Gut. 1993;34:386–391.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Asano T, McLeod RS. Dietary fibre for the prevention of colorectal adenomas and carcinomas. Cochrane Database Syst Rev. 2002;003430.

Download references

Acknowledgments

We would like to thank Rachel C. Wright for generation of the figures. Grant support was provided by the Allen Endowed Chair in Nutrition and Chronic Disease Prevention and the National Institutes of Health (R21-CA245456 and R35-CA197707).

Author information

Authors and Affiliations

  1. Department of Nutrition, Texas A&M University, College Station, TX, USA

    Robert S. Chapkin

  2. Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX, USA

    Robert S. Chapkin

  3. Program in Integrative Nutrition and Complex Diseases, Texas A&M University, College Station, TX, USA

    Robert S. Chapkin

  4. Public Health Sciences Division, and Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    Sandi L. Navarro, Meredith A. J. Hullar & Johanna W. Lampe

  5. School of Public Health, University of Washington, Seattle, WA, USA

    Johanna W. Lampe

Authors
  1. Robert S. Chapkin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sandi L. Navarro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Meredith A. J. Hullar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Johanna W. Lampe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert S. Chapkin.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chapkin, R.S., Navarro, S.L., Hullar, M.A.J. et al. Diet and Gut Microbes Act Coordinately to Enhance Programmed Cell Death and Reduce Colorectal Cancer Risk. Dig Dis Sci 65, 840–851 (2020). https://doi.org/10.1007/s10620-020-06106-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-020-06106-8

Keywords

Search

Navigation