Omega-3 PUFAs and gut microbiota: A preventive approach for colorectal cancer


Submitted: July 6, 2021
Accepted: November 20, 2021
Published: November 24, 2021
Abstract Views: 1045
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Authors

  • Marco Giammanco Department of Surgery, Oncologicical and Stomatological Sciences (Di.Chir.On.S), University Hospital Policlinico Paolo Giaccone of Palermo, Palermo, Italy.
  • Margherita Mazzola Institute of Human Anatomy and Histology, Department of Biomedicine, Neurosciences and Advanced Diagnostics, (BIND), University Hospital Policlinico Paolo Giaccone of Palermo, Palermo, Italy.
  • Manfredi Marco Giammanco Department of Human Pathology in Adulthood and Childhood “G. Barresi”, Medical School University of Messina, Messina, Italy.
  • Giovanni Tomasello Institute of Human Anatomy and Histology, Department of Biomedicine, Neurosciences and Advanced Diagnostics, (BIND), University Hospital Policlinico Paolo Giaccone of Palermo, Palermo, Italy.
  • Francesco Carini Institute of Human Anatomy and Histology, Department of Biomedicine, Neurosciences and Advanced Diagnostics, (BIND), University Hospital Policlinico Paolo Giaccone of Palermo, Palermo, Italy.

The influence of diet on the composition of the intestinal microbiota and related pathologies has been known for some time. Some classes of nutrients, such as fatty acids belonging to the omega 3 series, have particular effects on the bacteria that make up the intestinal microbiota. ω-3 PUFAs affect the gut microbiota in three different ways: by modulating the type and abundance of intestinal bacteria, by regulate SCFAs levels, and by alter the levels of proinflammatory mediators. Through these modalities, ω-3 PUFAs could be useful for the prevention of intestinal diseases such as Colorectal Cancer (CRC). The ability of ω-3 PUFAs to modulate the intestinal inflammatory response, to preserve the integrity of the intestinal mucosa and to modulate the bacterial composition of the intestine, could be useful as a preventive strategic approach to hinder the development of CRC.


Weir TL, Trikha SRJ, Thompson HJ. Diet and cancer risk reduction: The role of diet-microbiota interactions and microbial metabolites. Semin Cancer Biol 2021;70:53-60. DOI: https://doi.org/10.1016/j.semcancer.2020.06.007

Gentile CL, Weir TL. The gut microbiota at the intersection of diet and human health. Science 2018;362:776-80. DOI: https://doi.org/10.1126/science.aau5812

Tomasello G, Mazzola M, Leone A, et al. Nutrition, oxidative stress and intestinal dysbiosis: Influence of diet on gut microbiota in inflammatory bowel diseases. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2016;160:461-6. DOI: https://doi.org/10.5507/bp.2016.052

Sartor RB, Mazmanian SK. Intestinal microbes in inflammatory bowel diseases. Am J Gastroenterol Suppl 2012;1:15-21. DOI: https://doi.org/10.1038/ajgsup.2012.4

Tralongo P, Tomasello G, Sinagra E, et al. The role of butyric acid as a protective agent against inflammatory bowel diseases. Euromediter Biomed J 2014;9:24-35.

Tomasello G, Tralongo P, Damiani P, et al. Dismicrobism in inflammatory bowel disease and colorectal cancer: Changes in response of colocytes. World J Gastroenterol 2014;20:18121-30. DOI: https://doi.org/10.3748/wjg.v20.i48.18121

Tomasello G, Zeenny MN, Giammanco M, et al. Intestinal microbiota mutualism and gastrointestinal diseases. Euromediterr Biomed J 2015;10;65-75.

Mazzola M, Carini F, Damiani P, et al. Inflammatory bowel disease and colorectal cancer, nutraceutical aspects. Euromediterr Biomed J 2016;11:123-9.

Agus A, Denizot J, Thévenot J, et al. Western diet induces a shift in microbiota composition enhancing susceptibility to adherent-invasive E. coli infection and intestinal inflammation. Sci Rep 2016;6:19032. DOI: https://doi.org/10.1038/srep19032

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. DOI: https://doi.org/10.1038/ncomms7342

Song M, Chan AT. Environmental factors, gut microbiota, and colorectal cancer prevention. Clin Gastroenterol Hepatol 2019;17:275-89. DOI: https://doi.org/10.1016/j.cgh.2018.07.012

World Cancer Research Fund/American Institute for Cancer Research. Continuous update project report: diet, nutrition, physical activity and colorectal cancer. Available from: wcrf.org/colorectal-cancer-2017

La Guardia M, Giammanco S, Di Majo D, et al. Omega 3 fatty acids: biological activity and effects on human health. Panminerva Med 2005;47:245-57.

Bang HO, Dyerberg J, Nielsen AB. Plasma lipid and lipoprotein pattern in Greenlandic West-coast Eskimos. Lancet 1971;1:1143-5 DOI: https://doi.org/10.1016/S0140-6736(71)91658-8

Dyerberg J, Bang HO. Haemostatic function and platelet polyunsaturated fatty acids in Eskimos. Lancet 1979;2:433-5. DOI: https://doi.org/10.1016/S0140-6736(79)91490-9

Società Italiana di Nutrizione Umana-SINU, 2014. LARN – Livelli di assunzione di riferimento per la popolazione italiana: LIPIDI. Available from: https://sinu.it/2019/07/09/lipidi/

Sudheendran S, Chang C and Deckelbaum, R. N-3 vs. saturated fatty acids: effects on the arterial wall. Prostaglandins Leukotrienes Essential Fatty Acids 2010;82:205-9. DOI: https://doi.org/10.1016/j.plefa.2010.02.020

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA 2001;285:2486–97. DOI: https://doi.org/10.1001/jama.285.19.2486

Guo XF, Li X, Shi M, Li D. n-3 polyunsaturated fatty acids and metabolic syndrome risk: A meta-analysis. Nutrients 2017;9:703. DOI: https://doi.org/10.3390/nu9070703

Grundy SM. Diagnosis and management of the metabolic syndrome an American heart association/national heart, lung, and blood institute scientific statement. Curr Opin Cardiol 2005;21:1–6. DOI: https://doi.org/10.1097/01.hco.0000200416.65370.a0

Dembinska A. Effects of dietary fat modification on insulin sensitivity and on other risk factors of the metabolic syndrome—LIPGENE: A European randomized dietary intervention. Int J Obes 2011;35:800–9. DOI: https://doi.org/10.1038/ijo.2010.209

Paniagua JA, Pérez-Martinez P, Gjelstad IM, et al. A low-fat high-carbohydrate diet supplemented with long-chain n-3 PUFA reduces the risk of the metabolic syndrome. Atherosclerosis 2011;218:443–50. DOI: https://doi.org/10.1016/j.atherosclerosis.2011.07.003

Su KP, Tseng PT, Lin PY, et al. Association of use of omega-3 polyunsaturated fatty acids with changes in severity of anxiety symptoms. JAMA Network Open 2018;1:e182327 DOI: https://doi.org/10.1001/jamanetworkopen.2018.2327

Hallahan B, Ryan T, Hibbeln JR, et al. Efficacy of omega-3 highly unsaturated fatty acids in the treatment of depression. Br J Psychiat 2016;209:192-201. DOI: https://doi.org/10.1192/bjp.bp.114.160242

Zhu Z, Jiang W, McGinley JN, et al. Mammary gland density predicts the cancer inhibitory activity of the N-3 to N-6 ratio of dietary fat. Cancer Prev Res (Phila) 2011;4:1675-85. DOI: https://doi.org/10.1158/1940-6207.CAPR-11-0175

D'Eliseo D, Velotti F. Omega-3 fatty acids and cancer cell cytotoxicity: Implications for multi-targeted cancer therapy. J Clin Med 2016;5:15. DOI: https://doi.org/10.3390/jcm5020015

Pogash TJ, El-Bayoumy K, Amin S, et al. Oxidized derivative of docosahexaenoic acid preferentially inhibit cell proliferation in triple negative over luminal breast cancer cells. In Vitro Cell Dev Biol Anim 2015;51:121-7. DOI: https://doi.org/10.1007/s11626-014-9822-6

Khadge S, Sharp JG, Thiele GM, et al. Fatty acid mediators in the tumor microenvironment. Adv Exp Med Biol 2020;1259:125-53 DOI: https://doi.org/10.1007/978-3-030-43093-1_8

Ishida T, Yoshida M, Arita M, et al. Resolvin E1, an endogenous lipid mediator derived from eicosapentaenoic acid, prevents dextran sulfate sodium-induced colitis. Inflamm Bowel Dis 2010;16:87-95. DOI: https://doi.org/10.1002/ibd.21029

Marcon R, Bento AF, Dutra RC, et al. Maresin 1, a proresolving lipid mediator derived from omega-3 polyunsaturated fatty acids, exerts protective actions in murine models of colitis. J Immunol 2013;191:4288-98. DOI: https://doi.org/10.4049/jimmunol.1202743

Gu Z, Lamont GJ, Lamont RJ, et al. Resolvin D1, resolvin D2 and maresin 1 activate the GSK3β anti-inflammatory axis in TLR4-engaged human monocytes. Innate Immun 2016;22:186-95. DOI: https://doi.org/10.1177/1753425916628618

Chiang N, De la Rosa X, Libreros S, Serhan CN. Novel Resolvin D2 receptor axis in infectious inflammation. J Immunol 2017;198:842–51. DOI: https://doi.org/10.4049/jimmunol.1601650

Gibson GR, Hutkins R, Sanders ME, et al. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol 2017;14:491-502. DOI: https://doi.org/10.1038/nrgastro.2017.75

Chapkin RS, Navarro SL, Hullar MAJ, Lampe JW. Diet and gut microbes act coordinately to enhance programmed cell death and reduce colorectal cancer risk. Dig Dis Sci 2020;65:840-51. DOI: https://doi.org/10.1007/s10620-020-06106-8

Patterson E, O’Doherty RM, 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;111:1905–17. DOI: https://doi.org/10.1017/S0007114514000117

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;5:3299–310. DOI: https://doi.org/10.3390/nu5083299

Fu Y, Wang Y, Gao H, et al. Associations among dietary Omega-3 polyunsaturated fatty acids, the gut microbiota, and intestinal immunity. Mediators Inflamm 2021;2021:8879227. DOI: https://doi.org/10.1155/2021/8879227

Cao W, Wang C, Chin Y, et al. DHA-phospholipids (DHA-PL) and EPA-phospholipids (EPA-PL) prevent intestinal dysfunction induced by chronic stress. Food Function 2019;10:277–88. DOI: https://doi.org/10.1039/C8FO01404C

Lauridsen C. Effects of dietary fatty acids on gut health and function of pigs pre- and post-weaning. J Animal Sci 2020;98:skaa086. DOI: https://doi.org/10.1093/jas/skaa086

Warner DR, Warner JB, Hardesty JE, et al. Decreased ω-6:ω-3 PUFA ratio attenuates ethanol-induced alterations in intestinal homeostasis, microbiota, and liver injury. J Lipid Res 2019;60:2034–49. DOI: https://doi.org/10.1194/jlr.RA119000200

Rinninella E, Raoul P, Cintoni M, et al. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms 2019;7:14. DOI: https://doi.org/10.3390/microorganisms7010014

Crovesy L, Masterson D, Rosado EL. Profile of the gut microbiota of adults with obesity: a systematic review. Eur J Clin Nutr 2020;74:1251–62. DOI: https://doi.org/10.1038/s41430-020-0607-6

PM Keller, M. Hombach, GV Bloemberg. 16S-rRNA-Gen-basierte Identifikation bakterieller infektionen. BIOspektrum 2010:755-8.

Onishi JC, Campbell S, Moreau M, et al. Bacterial communities in the small intestine respond differently to those in the caecum and colon in mice fed low- and high-fat diets. Microbiology (Reading) 2017;163:1189-97. DOI: https://doi.org/10.1099/mic.0.000496

Schoeler M, Caesar R. Dietary lipids, gut microbiota and lipid metabolism. Rev Endocrine Metabolic Disord 2019;20:461–72. DOI: https://doi.org/10.1007/s11154-019-09512-0

Hutchinson AN, Tingö L, Brummer RJ. The potential effects of probiotics and ω-3 fatty acids on chronic low-grade inflammation. Nutrients 2020;12:2402. DOI: https://doi.org/10.3390/nu12082402

Husson MO, Ley D, Portal C, et al. Modulation of host defence against bacterial and viral infections by omega-3 polyunsaturated fatty acids. J Infect 2016;73:523-35. DOI: https://doi.org/10.1016/j.jinf.2016.10.001

Babcock TA, Kurland A, Helton WS, et al. Inhibition of activator protein-1 transcription factor activation by omega-3 fatty acid modulation of mitogen-activated protein kinase signaling kinases. JPEN J Parenter Enteral Nutr 2003;27:176-80. DOI: https://doi.org/10.1177/0148607103027003176

Kim JY, Lim K, Kim KH, et al. N-3 polyunsaturated fatty acids restore Th17 and Treg balance in collagen antibody-induced arthritis. PLoS One 2018;13:e0194331. DOI: https://doi.org/10.1371/journal.pone.0194331

Carini F, Mazzola M, Rappa F, et al. Colorectal Carcinogenesis: Role of Oxidative Stress and Antioxidants. Anticancer Res 2017;37:4759-66. DOI: https://doi.org/10.21873/anticanres.11882

Costantini L, Merendino N. Polyunsaturated fatty acids and microbiota relationship: Implications in cancer onset and treatment. J Clin Med 2020;9:3490. DOI: https://doi.org/10.3390/jcm9113490

Prossomariti A, Scaioli E, Piazzi G, et al. Short-term treatment with eicosapentaenoic acid improves inflammation and aspects colonic differentiation markers and microbiota in patients with ulcerative colitis. Sci Rep 2017;7:7458. DOI: https://doi.org/10.1038/s41598-017-07992-1

Tu M, Wang W, Zhang G, Hammock BD. ω-3 Polyunsaturated fatty acids on colonic inflammation and colon cancer: Roles of lipid-metabolizing enzymes involved. Nutrients 2020;12:3301. DOI: https://doi.org/10.3390/nu12113301

Kantor ED, Lampe JW, Peters U, et al. Long-chain omega-3 polyunsaturated fatty acid intake and risk of colorectal cancer. Nutr Cancer 2014;66:716–27. DOI: https://doi.org/10.1080/01635581.2013.804101

Aglago EK, Huybrechts I, Murphy N, et al. Consumption of fish and long-chain n-3 polyunsaturated fatty acids is associated with reduced risk of colorectal cancer in a large european cohort. Clin Gastroenterol Hepatol 2020;18:654–66. DOI: https://doi.org/10.1016/j.cgh.2019.06.031

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 DOI: https://doi.org/10.1136/gut.2009.200642

Michalak A, Mosińska P, Fichna J. Polyunsaturated fatty acids and their derivatives: Therapeutic value for inflammatory, functional gastrointestinal disorders, and colorectal cancer. Front Pharmacol 2016;7:459. DOI: https://doi.org/10.3389/fphar.2016.00459

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. DOI: https://doi.org/10.1136/gutjnl-2013-306445

Chapkin RS, Navarro SL, Hullar MAJ, Lampe JW. Diet and Gut Microbes Act Coordinately to Enhance Programmed Cell Death and Reduce Colorectal Cancer Risk. Dig Dis Sci 2020;65:840-51. DOI: https://doi.org/10.1007/s10620-020-06106-8

Giammanco, M., Mazzola, M., Giammanco, M. M., Tomasello, G., & Carini, F. (2021). Omega-3 PUFAs and gut microbiota: A preventive approach for colorectal cancer. Journal of Biological Research - Bollettino Della Società Italiana Di Biologia Sperimentale, 94(2). https://doi.org/10.4081/jbr.2021.9954

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