Skip to main content
SpringerLink
Log in

Long-chain polyunsaturated fatty acids influence colorectal cancer progression via the interactions between the intestinal microflora and the macrophages

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

The metabolism of long-chain polyunsaturated fatty acids (LCPUFAs) is closely associated with the risk and progression of colorectal cancer (CRC). This paper aims to investigate the role of LCPUFA in the crosstalk between intestinal microflora and macrophages, as well as the effects of these three parties on the progression of CRC. The metabolism and function of LCPUFA play important roles in regulating the composition of the human gut microflora and participating in the regulation of inflammation, ultimately affecting macrophage function and polarization, which is crucial in the tumor microenvironment. The effects of LCPUFA on cellular interactions between the two species can ultimately influence the progression of CRC. In this review, we explore the molecular mechanisms and clinical applications of LCPUFA in the interactions between intestinal microflora and intestinal macrophages, as well as its significance for CRC progression. Furthermore, we reveal the role of LCPUFA in the construction of the CRC microenvironment and explore the key nodes of the interactions between intestinal flora and intestinal macrophages in the environment. It provides potential targets for the metabolic diagnosis and treatment of CRC.

Graphical abstract

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

Abbreviations

ALA:

α-Linolenic acid

CRC :

Colorectal cancer

DHA:

Docosahexaenoic acid

EPA :

Eicosapentaenoic acid

LCPUFAs:

Long-chain polyunsaturated fatty acids

n-3 PUFAs:

N-3 polyunsaturated fatty acids

n-6 PUFAs:

N-6 polyunsaturated fatty acids

PGE-2:

Prostaglandin E-2

TAMs :

Tumor-associated macrophages

References

  1. Siegel RL, Miller KD, Fuchs HE, Jemal A (2022) Cancer statistics 2022. CA Cancer J Clin. https://doi.org/10.3322/caac.21708

    Article  PubMed  Google Scholar 

  2. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al (2021) Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209–249. https://doi.org/10.3322/caac.21660

    Article  PubMed  Google Scholar 

  3. Norat T, Bingham S, Ferrari P, Slimani N, Jenab M, Mazuir M et al (2005) Meat, fish, and colorectal cancer risk: The european prospective investigation into cancer and nutrition. J Natl Cancer Inst 97:906–916

    Article  PubMed  Google Scholar 

  4. Zhang J, Zhang L, Ye X, Chen L, Zhang L, Gao Y et al (2013) Characteristics of fatty acid distribution is associated with colorectal cancer prognosis. Prostaglandins Leukot Essent Fatty Acids 88:355–360. https://doi.org/10.1016/j.plefa.2013.02.005

    Article  CAS  PubMed  Google Scholar 

  5. Juloski T, J, Popovic T, Martacic JD, V Cuk V, S Milic Perovic M, S Stankovic M, et al (2021) Fatty acid in colorectal cancer in adult and aged patients of both sexes. J Buon 26:1898–1907

    Google Scholar 

  6. Fernández-Bañares F, Esteve M, Navarro E, Cabré E, Boix J, Abad-Lacruz A et al (1996) Changes of the mucosal n3 and n6 fatty acid status occur early in the colorectal adenoma-carcinoma sequence. Gut 38:254–259

    Article  PubMed  PubMed Central  Google Scholar 

  7. Liu M, Zhou L, Zhang B, He M, Dong X, Lin X et al (2016) Elevation of n-3/n-6 pufas ratio suppresses mtorc1 and prevents colorectal carcinogenesis associated with apc mutation. Oncotarget 7:76944–76954. https://doi.org/10.18632/oncotarget.12759

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lee JY, Sim T-B, Lee J-E, Na H-K (2017) Chemopreventive and chemotherapeutic effects of fish oil derived omega-3 polyunsaturated fatty acids on colon carcinogenesis. Clin Nutr Res 6:147–160. https://doi.org/10.7762/cnr.2017.6.3.147

    Article  PubMed  PubMed Central  Google Scholar 

  9. Liu J, Li X, Hou J, Sun J, Guo N, Wang Z (2021) Dietary intake of n-3 and n-6 polyunsaturated fatty acids and risk of cancer: Meta-analysis of data from 32 studies. Nutr Cancer 73:901–913. https://doi.org/10.1080/01635581.2020.1779321

    Article  CAS  PubMed  Google Scholar 

  10. Zhou B, Yuan Y, Zhang S, Guo C, Li X, Li G et al (2020) Intestinal flora and disease mutually shape the regional immune system in the intestinal tract. Front Immunol 11:575. https://doi.org/10.3389/fimmu.2020.00575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cheng Y, Ling Z, Li L (2020) The intestinal microbiota and colorectal cancer. Front Immunol 11:615056. https://doi.org/10.3389/fimmu.2020.615056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Arthur JC, Perez-Chanona E, Mühlbauer M, Tomkovich S, Uronis JM, Fan T-J et al (2012) Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338:120–123. https://doi.org/10.1126/science.1224820

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Rivollier A, He J, Kole A, Valatas V, Kelsall BL (2012) Inflammation switches the differentiation program of ly6chi monocytes from antiinflammatory macrophages to inflammatory dendritic cells in the colon. J Exp Med 209:139–155. https://doi.org/10.1084/jem.20101387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Fu Y, Wang Y, Gao H, Li D, Jiang R, Ge L et al (2021) Associations among dietary omega-3 polyunsaturated fatty acids, the gut microbiota, and intestinal immunity. Mediators Inflamm 2021:8879227. https://doi.org/10.1155/2021/8879227

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Horigome A, Okubo R, Hamazaki K, Kinoshita T, Katsumata N, Uezono Y et al (2019) Association between blood omega-3 polyunsaturated fatty acids and the gut microbiota among breast cancer survivors. Benef Microbes 10:751–758. https://doi.org/10.3920/BM2019.0034

    Article  CAS  PubMed  Google Scholar 

  16. O’Mahony C, Amamou A, Ghosh S (2022) Diet-microbiota interplay: An emerging player in macrophage plasticity and intestinal health. Int J Mol Sci. https://doi.org/10.3390/ijms23073901

    Article  PubMed  PubMed Central  Google Scholar 

  17. Ohue-Kitano R, Yasuoka Y, Goto T, Kitamura N, Park S-B, Kishino S et al (2018) Α-linolenic acid-derived metabolites from gut lactic acid bacteria induce differentiation of anti-inflammatory m2 macrophages through g protein-coupled receptor 40. FASEB J 32:304–318. https://doi.org/10.1096/fj.201700273R

    Article  CAS  PubMed  Google Scholar 

  18. Mahida YR (2000) The key role of macrophages in the immunopathogenesis of inflammatory bowel disease. Inflamm Bowel Dis 6:21–33

    Article  CAS  PubMed  Google Scholar 

  19. Nakamura MT, Yudell BE, Loor JJ (2014) Regulation of energy metabolism by long-chain fatty acids. Prog Lipid Res 53:124–144. https://doi.org/10.1016/j.plipres.2013.12.001

    Article  CAS  PubMed  Google Scholar 

  20. Knottnerus SJG, Bleeker JC, Wüst RCI, Ferdinandusse S, Ijlst L, Wijburg FA et al (2018) Disorders of mitochondrial long-chain fatty acid oxidation and the carnitine shuttle. Rev Endocr Metab Disord. https://doi.org/10.1007/s11154-018-9448-1

    Article  PubMed  PubMed Central  Google Scholar 

  21. Janssen CIF, Kiliaan AJ (2014) Long-chain polyunsaturated fatty acids (lcpufa) from genesis to senescence: The influence of lcpufa on neural development, aging, and neurodegeneration. Prog Lipid Res. https://doi.org/10.1016/j.plipres.2013.10.002

    Article  PubMed  Google Scholar 

  22. Shahidi F, Ambigaipalan P (2018) Omega-3 polyunsaturated fatty acids and their health benefits. Annu Rev Food Sci Technol 9:345–381. https://doi.org/10.1146/annurev-food-111317-095850

    Article  CAS  PubMed  Google Scholar 

  23. D’Angelo S, Motti ML, Meccariello R (2020) Ω-3 and ω-6 polyunsaturated fatty acids, obesity and cancer. Nutrients. https://doi.org/10.3390/nu12092751

    Article  PubMed  PubMed Central  Google Scholar 

  24. Muhlhausler BS, Ailhaud GP (2013) Omega-6 polyunsaturated fatty acids and the early origins of obesity. Curr Opin Endocrinol Diabetes Obes 20:56–61. https://doi.org/10.1097/MED.0b013e32835c1ba7

    Article  CAS  PubMed  Google Scholar 

  25. Yang LG, Song ZX, Yin H, Wang YY, Shu GF, Lu HX et al (2016) Low n-6/n-3 pufa ratio improves lipid metabolism, inflammation, oxidative stress and endothelial function in rats using plant oils as n-3 fatty acid source. Lipids 51:49–59. https://doi.org/10.1007/s11745-015-4091-z

    Article  CAS  PubMed  Google Scholar 

  26. Vetrani C, Maukonen J, Bozzetto L, Della Pepa G, Vitale M, Costabile G et al (2020) Diets naturally rich in polyphenols and/or long-chain n-3 polyunsaturated fatty acids differently affect microbiota composition in high-cardiometabolic-risk individuals. Acta Diabetol 57:853–860. https://doi.org/10.1007/s00592-020-01494-9

    Article  CAS  PubMed  Google Scholar 

  27. Adak A, Khan MR (2019) An insight into gut microbiota and its functionalities. Cell Mol Life Sci 76:473–493. https://doi.org/10.1007/s00018-018-2943-4

    Article  CAS  PubMed  Google Scholar 

  28. Lynch SV, Pedersen O (2016) The human intestinal microbiome in health and disease. N Engl J Med 375:2369–2379

    Article  CAS  PubMed  Google Scholar 

  29. Angelucci F, Cechova K, Amlerova J, Hort J (2019) Antibiotics, gut microbiota, and alzheimer’s disease. J Neuroinflammation 16:108. https://doi.org/10.1186/s12974-019-1494-4

    Article  PubMed  PubMed Central  Google Scholar 

  30. Heintz-Buschart A, Wilmes P (2018) Human gut microbiome: Function matters. Trends Microbiol 26:563–574. https://doi.org/10.1016/j.tim.2017.11.002

    Article  CAS  PubMed  Google Scholar 

  31. Vaughn AC, Cooper EM, DiLorenzo PM, O’Loughlin LJ, Konkel ME, Peters JH et al (2017) Energy-dense diet triggers changes in gut microbiota, reorganization of gut-brain vagal communication and increases body fat accumulation. Acta Neurobiol Exp (Wars) 77:18–30

    Article  PubMed  Google Scholar 

  32. Kuzma J, Chmelař D, Hájek M, Lochmanová A, Čižnár I, Rozložník M et al (2020) The role of intestinal microbiota in the pathogenesis of colorectal carcinoma. Folia Microbiol (Praha) 65:17–24. https://doi.org/10.1007/s12223-019-00706-2

    Article  CAS  PubMed  Google Scholar 

  33. Schoeler M, Caesar R (2019) Dietary lipids, gut microbiota and lipid metabolism. Rev Endocr Metab Disord 20:461–472. https://doi.org/10.1007/s11154-019-09512-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Miyamoto J, Mizukure T, Park S-B, Kishino S, Kimura I, Hirano K et al (2015) 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 290:2902–2918. https://doi.org/10.1074/jbc.M114.610733

    Article  CAS  PubMed  Google Scholar 

  35. Cândido FG, Valente FX, Grześkowiak ŁM, Moreira APB, Rocha DMUP, Alfenas RdCG (2018) Impact of dietary fat on gut microbiota and low-grade systemic inflammation: Mechanisms and clinical implications on obesity. Int J Food Sci Nutr 69:125–143. https://doi.org/10.1080/09637486.2017.1343286

    Article  CAS  PubMed  Google Scholar 

  36. Watson H, Mitra S, Croden FC, Taylor M, Wood HM, Perry SL et al (2018) A randomised trial of the effect of omega-3 polyunsaturated fatty acid supplements on the human intestinal microbiota. Gut 67:1974–1983. https://doi.org/10.1136/gutjnl-2017-314968

    Article  CAS  PubMed  Google Scholar 

  37. Robertson RC, Seira Oriach C, Murphy K, Moloney GM, Cryan JF, Dinan TG et al (2017) Omega-3 polyunsaturated fatty acids critically regulate behaviour and gut microbiota development in adolescence and adulthood. Brain Behav Immun 59:21–37. https://doi.org/10.1016/j.bbi.2016.07.145

    Article  CAS  PubMed  Google Scholar 

  38. Caesar R, Tremaroli V, Kovatcheva-Datchary P, Cani PD, Bäckhed F (2015) Crosstalk between gut microbiota and dietary lipids aggravates wat inflammation through tlr signaling. Cell Metab 22:658–668. https://doi.org/10.1016/j.cmet.2015.07.026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Moreira Lopes TC, Mosser DM, Gonçalves R (2020) Macrophage polarization in intestinal inflammation and gut homeostasis. Inflamm Res 69:1163–1172. https://doi.org/10.1007/s00011-020-01398-y

    Article  CAS  PubMed  Google Scholar 

  40. Shapouri-Moghaddam A, Mohammadian S, Vazini H, Taghadosi M, Esmaeili S-A, Mardani F et al (2018) Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol 233:6425–6440. https://doi.org/10.1002/jcp.26429

    Article  CAS  PubMed  Google Scholar 

  41. Boutilier AJ, Elsawa SF (2021) Macrophage polarization states in the tumor microenvironment. Int J Mol Sci. https://doi.org/10.3390/ijms22136995

    Article  PubMed  PubMed Central  Google Scholar 

  42. Yan J, Horng T (2020) Lipid metabolism in regulation of macrophage functions. Trends Cell Biol 30:979–989. https://doi.org/10.1016/j.tcb.2020.09.006

    Article  CAS  PubMed  Google Scholar 

  43. Liu F, Smith AD, Solano-Aguilar G, Wang TTY, Pham Q, Beshah E et al (2020) Mechanistic insights into the attenuation of intestinal inflammation and modulation of the gut microbiome by krill oil using in vitro and in vivo models. Microbiome 8:83. https://doi.org/10.1186/s40168-020-00843-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Oliver E, McGillicuddy F, Phillips C, Toomey S, Roche HM (2010) The role of inflammation and macrophage accumulation in the development of obesity-induced type 2 diabetes mellitus and the possible therapeutic effects of long-chain n-3 pufa. Proc Nutr Soc 69:232–243. https://doi.org/10.1017/S0029665110000042

    Article  CAS  PubMed  Google Scholar 

  45. Lefèvre L, Galès A, Olagnier D, Bernad J, Perez L, Burcelin R et al (2010) Pparγ ligands switched high fat diet-induced macrophage m2b polarization toward m2a thereby improving intestinal candida elimination. PLoS ONE 5:e12828. https://doi.org/10.1371/journal.pone.0012828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Yang Y, Li L, Xu C, Wang Y, Wang Z, Chen M et al (2020) Cross-talk between the gut microbiota and monocyte-like macrophages mediates an inflammatory response to promote colitis-associated tumourigenesis. Gut 70:1495–1506. https://doi.org/10.1136/gutjnl-2020-320777

    Article  CAS  PubMed  Google Scholar 

  47. Keum N, Giovannucci E (2019) Global burden of colorectal cancer: Emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol 16:713–732. https://doi.org/10.1038/s41575-019-0189-8

    Article  PubMed  Google Scholar 

  48. Monk JM, Liddle DM, Hutchinson AL, Wu W, Lepp D, Ma DWL et al (2019) Fish oil supplementation to a high-fat diet improves both intestinal health and the systemic obese phenotype. J Nutr Biochem 72:108216. https://doi.org/10.1016/j.jnutbio.2019.07.007

    Article  CAS  PubMed  Google Scholar 

  49. Perez LG, Kempski J, McGee HM, Pelzcar P, Agalioti T, Giannou A et al (2020) Tgf-β signaling in th17 cells promotes il-22 production and colitis-associated colon cancer. Nat Commun 11:2608. https://doi.org/10.1038/s41467-020-16363-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Punkenburg E, Vogler T, Büttner M, Amann K, Waldner M, Atreya R et al (2016) Batf-dependent th17 cells critically regulate il-23 driven colitis-associated colon cancer. Gut 65:1139–1150. https://doi.org/10.1136/gutjnl-2014-308227

    Article  CAS  PubMed  Google Scholar 

  51. Monk JM, Jia Q, Callaway E, Weeks B, Alaniz RC, McMurray DN et al (2012) Th17 cell accumulation is decreased during chronic experimental colitis by (n-3) pufa in fat-1 mice. J Nutr 142:117–124. https://doi.org/10.3945/jn.111.147058

    Article  CAS  PubMed  Google Scholar 

  52. Dulai PS, Sandborn WJ, Gupta S (2016) Colorectal cancer and dysplasia in inflammatory bowel disease: A review of disease epidemiology, pathophysiology, and management. Cancer Prev Res (Phila) 9:887–894

    Article  PubMed  Google Scholar 

  53. Dong J, Liang W, Wang T, Sui J, Wang J, Deng Z et al (2019) Saponins regulate intestinal inflammation in colon cancer and ibd. Pharmacol Res 144:66–72. https://doi.org/10.1016/j.phrs.2019.04.010

    Article  CAS  PubMed  Google Scholar 

  54. Zhang O, Zhang J (2015) Atorvastatin promotes human monocyte differentiation toward alternative m2 macrophages through p38 mitogen-activated protein kinase-dependent peroxisome proliferator-activated receptor γ activation. Int Immunopharmacol 26:58–64. https://doi.org/10.1016/j.intimp.2015.03.005

    Article  CAS  PubMed  Google Scholar 

  55. Desreumaux P, Dubuquoy L, Nutten S, Peuchmaur M, Englaro W, Schoonjans K et al (2001) Attenuation of colon inflammation through activators of the retinoid x receptor (rxr)/peroxisome proliferator-activated receptor gamma (ppargamma) heterodimer. A basis for new therapeutic strategies. J Exp Med 193:827–838

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Liberato MV, Nascimento AS, Ayers SD, Lin JZ, Cvoro A, Silveira RL et al (2012) Medium chain fatty acids are selective peroxisome proliferator activated receptor (ppar) γ activators and pan-ppar partial agonists. PLoS ONE 7:e36297. https://doi.org/10.1371/journal.pone.0036297

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Zúñiga J, Cancino M, Medina F, Varela P, Vargas R, Tapia G et al (2011) N-3 pufa supplementation triggers ppar-α activation and ppar-α/nf-κb interaction: Anti-inflammatory implications in liver ischemia-reperfusion injury. PLoS ONE 6:e28502. https://doi.org/10.1371/journal.pone.0028502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Bagga D, Wang L, Farias-Eisner R, Glaspy JA, Reddy ST (2003) Differential effects of prostaglandin derived from omega-6 and omega-3 polyunsaturated fatty acids on cox-2 expression and il-6 secretion. Proc Natl Acad Sci U S A 100:1751–1756

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. De Simone V, Franzè E, Ronchetti G, Colantoni A, Fantini MC, Di Fusco D et al (2015) Th17-type cytokines, il-6 and tnf-α synergistically activate stat3 and nf-kb to promote colorectal cancer cell growth. Oncogene 34:3493–3503. https://doi.org/10.1038/onc.2014.286

    Article  CAS  PubMed  Google Scholar 

  60. Zhang S, Gang X, Yang S, Cui M, Sun L, Li Z et al (2021) The alterations in and the role of the th17/treg balance in metabolic diseases. Front Immunol 12:678355. https://doi.org/10.3389/fimmu.2021.678355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Wastyk HC, Fragiadakis GK, Perelman D, Dahan D, Merrill BD, Yu FB et al (2021) Gut-microbiota-targeted diets modulate human immune status. Cell. https://doi.org/10.1016/j.cell.2021.06.019

    Article  PubMed  PubMed Central  Google Scholar 

  62. Kawashima H (2019) Intake of arachidonic acid-containing lipids in adult humans: Dietary surveys and clinical trials. Lipids Health Dis 18:101. https://doi.org/10.1186/s12944-019-1039-y

    Article  PubMed  PubMed Central  Google Scholar 

  63. Firmansyah A, Dwipoerwantoro PG, Kadim M, Alatas S, Conus N, Lestarina L et al (2011) Improved growth of toddlers fed a milk containing synbiotics. Asia Pac J Clin Nutr 20:69–76

    CAS  PubMed  Google Scholar 

  64. Weng YJ, Gan HY, Li X, Huang Y, Li ZC, Deng HM et al (2019) Correlation of diet, microbiota and metabolite networks in inflammatory bowel disease. J Dig Dis 20:447–459. https://doi.org/10.1111/1751-2980.12795

    Article  CAS  PubMed  Google Scholar 

  65. Lichtenstern CR, Ngu RK, Shalapour S, Karin M (2020) Immunotherapy, inflammation and colorectal cancer. Cells. https://doi.org/10.3390/cells9030618

    Article  PubMed  PubMed Central  Google Scholar 

  66. Schmitt H, Neurath MF, Atreya R (2021) Role of the il23/il17 pathway in crohn’s disease. Front Immunol 12:622934. https://doi.org/10.3389/fimmu.2021.622934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Poland M, Ten Klooster JP, Wang Z, Pieters R, Boekschoten M, Witkamp R et al (2016) Docosahexaenoyl serotonin, an endogenously formed n-3 fatty acid-serotonin conjugate has anti-inflammatory properties by attenuating il-23-il-17 signaling in macrophages. Biochim Biophys Acta 1861:2020–2028. https://doi.org/10.1016/j.bbalip.2016.09.012

    Article  CAS  PubMed  Google Scholar 

  68. Oliver E, McGillicuddy FC, Harford KA, Reynolds CM, Phillips CM, Ferguson JF et al (2012) Docosahexaenoic acid attenuates macrophage-induced inflammation and improves insulin sensitivity in adipocytes-specific differential effects between lc n-3 pufa. J Nutr Biochem 23:1192–1200. https://doi.org/10.1016/j.jnutbio.2011.06.014

    Article  CAS  PubMed  Google Scholar 

  69. Isidro RA, Appleyard CB (2016) Colonic macrophage polarization in homeostasis, inflammation, and cancer. Am J Physiol Gastrointest Liver Physiol 311:G59–G73. https://doi.org/10.1152/ajpgi.00123.2016

    Article  PubMed  PubMed Central  Google Scholar 

  70. Yang Y, Li L, Xu C, Wang Y, Wang Z, Chen M et al (2020) Cross-talk between the gut microbiota and monocyte-like macrophages mediates an inflammatory response to promote colitis-associated tumourigenesis. Gut. https://doi.org/10.1136/gutjnl-2020-320777

    Article  PubMed  Google Scholar 

  71. Ludwig T, Worsch S, Heikenwalder M, Daniel H, Hauner H, Bader BL (2013) Metabolic and immunomodulatory effects of n-3 fatty acids are different in mesenteric and epididymal adipose tissue of diet-induced obese mice. Am J Physiol Endocrinol Metab 304:E1140–E1156. https://doi.org/10.1152/ajpendo.00171.2012

    Article  CAS  PubMed  Google Scholar 

  72. Yashiro M (2014) Ulcerative colitis-associated colorectal cancer. World J Gastroenterol 20:16389–16397. https://doi.org/10.3748/wjg.v20.i44.16389

    Article  PubMed  PubMed Central  Google Scholar 

  73. Belcheva A, Irrazabal T, Robertson SJ, Streutker C, Maughan H, Rubino S et al (2014) Gut microbial metabolism drives transformation of msh2-deficient colon epithelial cells. Cell 158:288–299. https://doi.org/10.1016/j.cell.2014.04.051

    Article  CAS  PubMed  Google Scholar 

  74. Costantini L, Molinari R, Farinon B, Merendino N (2017) Impact of omega-3 fatty acids on the gut microbiota. Int J Mol Sci. https://doi.org/10.3390/ijms18122645

    Article  PubMed  PubMed Central  Google Scholar 

  75. Zhao J, Shi P, Sun Y, Sun J, Dong J-N, Wang H-G et al (2015) Dha protects against experimental colitis in il-10-deficient mice associated with the modulation of intestinal epithelial barrier function. Br J Nutr 114:181–188

    Article  CAS  PubMed  Google Scholar 

  76. Aglago EK, Huybrechts I, Murphy N, Casagrande C, Nicolas G, Pischon T et al (2020) 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. https://doi.org/10.1016/j.cgh.2019.06.031

    Article  PubMed  Google Scholar 

  77. Parolini C (2019) Effects of fish n-3 pufas on intestinal microbiota and immune system. Mar Drugs. https://doi.org/10.3390/md17060374

    Article  PubMed  PubMed Central  Google Scholar 

  78. Faghfoori Z, Faghfoori MH, Saber A, Izadi A, Yari KA (2021) Anticancer effects of bifidobacteria on colon cancer cell lines. Cancer Cell Int 21:258. https://doi.org/10.1186/s12935-021-01971-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Shama S, Liu W (2020) Omega-3 fatty acids and gut microbiota: A reciprocal interaction in nonalcoholic fatty liver disease. Dig Dis Sci 65:906–910. https://doi.org/10.1007/s10620-020-06117-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Selmin OI, Papoutsis AJ, Hazan S, Smith C, Greenfield N, Donovan MG et al (2021) 6 high fat diet induces gut microbiome dysbiosis and colonic inflammation. Int J Mol Sci. https://doi.org/10.3390/ijms22136919

    Article  PubMed  PubMed Central  Google Scholar 

  81. Wang CZ, Huang WH, Zhang CF, Wan JY, Wang Y, Yu C et al (2018) Role of intestinal microbiome in american ginseng-mediated colon cancer prevention in high fat diet-fed aom/dss mice [corrected]. Clin Transl Oncol 20:302–312. https://doi.org/10.1007/s12094-017-1717-z

    Article  CAS  PubMed  Google Scholar 

  82. Wang H, Tian T, Zhang J (2021) Tumor-associated macrophages (tams) in colorectal cancer (crc): From mechanism to therapy and prognosis. Int J Mol Sci. https://doi.org/10.3390/ijms22168470

    Article  PubMed  PubMed Central  Google Scholar 

  83. Wei C, Yang C, Wang S, Shi D, Zhang C, Lin X et al (2019) Crosstalk between cancer cells and tumor associated macrophages is required for mesenchymal circulating tumor cell-mediated colorectal cancer metastasis. Mol Cancer 18:64. https://doi.org/10.1186/s12943-019-0976-4

    Article  PubMed  PubMed Central  Google Scholar 

  84. Wu H, Han Y, Rodriguez Sillke Y, Deng H, Siddiqui S, Treese C et al (2019) Lipid droplet-dependent fatty acid metabolism controls the immune suppressive phenotype of tumor-associated macrophages. EMBO Mol Med 11:e10698. https://doi.org/10.15252/emmm.201910698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Kawano A, Ariyoshi W, Yoshioka Y, Hikiji H, Nishihara T, Okinaga T (2019) Docosahexaenoic acid enhances m2 macrophage polarization via the p38 signaling pathway and autophagy. J Cell Biochem 120:12604–12617. https://doi.org/10.1002/jcb.28527

    Article  CAS  PubMed  Google Scholar 

  86. Fridman WH, Pagès F, Sautès-Fridman C, Galon J (2012) The immune contexture in human tumours: Impact on clinical outcome. Nat Rev Cancer 12:298–306. https://doi.org/10.1038/nrc3245

    Article  CAS  PubMed  Google Scholar 

  87. Corn KC, Windham MA, Rafat M (2020) Lipids in the tumor microenvironment: From cancer progression to treatment. Prog Lipid Res 80:101055. https://doi.org/10.1016/j.plipres.2020.101055

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Su P, Wang Q, Bi E, Ma X, Liu L, Yang M et al (2020) Enhanced lipid accumulation and metabolism are required for the differentiation and activation of tumor-associated macrophages. Cancer Res 80:1438–1450. https://doi.org/10.1158/0008-5472.CAN-19-2994

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Hernandez-Quiles M, Broekema MF, Kalkhoven E (2021) Ppargamma in metabolism, immunity, and cancer: Unified and diverse mechanisms of action. Front Endocrinol (Lausanne) 12:624112. https://doi.org/10.3389/fendo.2021.624112

    Article  PubMed  Google Scholar 

  90. Meng Q, Zhang Y, Li J, Shi B, Ma Q, Shan A (2022) Lycopene affects intestinal barrier function and the gut microbiota in weaned piglets via antioxidant signaling regulation. J Nutr 152:2396–2408. https://doi.org/10.1093/jn/nxac208

    Article  CAS  PubMed  Google Scholar 

  91. Skrzydlewska E, Sulkowski S, Koda M, Zalewski B, Kanczuga-Koda L, Sulkowska M (2005) Lipid peroxidation and antioxidant status in colorectal cancer. World J Gastroenterol 11:403–406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Wang X, Yang Y, Huycke MM (2015) Commensal bacteria drive endogenous transformation and tumour stem cell marker expression through a bystander effect. Gut 64:459–468. https://doi.org/10.1136/gutjnl-2014-307213

    Article  CAS  PubMed  Google Scholar 

  93. Wang X, Yang Y, Moore DR, Nimmo SL, Lightfoot SA, Huycke MM (2012) 4-hydroxy-2-nonenal mediates genotoxicity and bystander effects caused by enterococcus faecalis-infected macrophages. Gastroenterology. https://doi.org/10.1053/j.gastro.2011.11.020

    Article  PubMed  PubMed Central  Google Scholar 

  94. Sundaram TS, Giromini C, Rebucci R, Baldi A (2020) Omega-3 polyunsaturated fatty acids counteract inflammatory and oxidative damage of non-transformed porcine enterocytes. Animals (Basel). https://doi.org/10.3390/ani10060956

    Article  PubMed  Google Scholar 

  95. Patterson E, O’ Doherty RM, Murphy EF, Wall R, O’ Sullivan O, Nilaweera K, et al (2014) Impact of dietary fatty acids on metabolic activity and host intestinal microbiota composition in c57bl/6j mice. Br J Nutr 111:1905–1917. https://doi.org/10.1017/S0007114514000117

    Article  CAS  PubMed  Google Scholar 

  96. Li R, Zhou R, Wang H, Li W, Pan M, Yao X et al (2019) Gut microbiota-stimulated cathepsin k secretion mediates tlr4-dependent m2 macrophage polarization and promotes tumor metastasis in colorectal cancer. Cell Death Differ 26:2447–2463. https://doi.org/10.1038/s41418-019-0312-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Chapkin RS, Navarro SL, Hullar MAJ, Lampe JW (2020) Diet and gut microbes act coordinately to enhance programmed cell death and reduce colorectal cancer risk. Dig Dis Sci 65:840–851. https://doi.org/10.1007/s10620-020-06106-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Sánchez-Alcoholado L, Ordóñez R, Otero A, Plaza-Andrade I, Laborda-Illanes A, Medina JA et al (2020) Gut microbiota-mediated inflammation and gut permeability in patients with obesity and colorectal cancer. Int J Mol Sci. https://doi.org/10.3390/ijms21186782

    Article  PubMed  PubMed Central  Google Scholar 

  99. Kong LC, Holmes BA, Cotillard A, Habi-Rachedi F, Brazeilles R, Gougis S et al (2014) Dietary patterns differently associate with inflammation and gut microbiota in overweight and obese subjects. PLoS ONE 9:e109434. https://doi.org/10.1371/journal.pone.0109434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

None.

Funding

This work was supported by The National Natural Science Foundation of China under Award Number 81572566, Natural Science Foundation of Guangdong Province under Award Number 2015A030310046 and 2016A030313674, Research Foundation Project of Guangdong Medical University under Award Number Z2015004 and Z2017005, Science and Technology Planning Project of Guangdong Province under Award Number 2016A020215224, and Graduate Education Innovation Program Project of Guangdong Province under Award Number 2022XSLT047 and 2022SFKC063.

Author information

Author notes

  1. Duo Peng, Yan Wang and Yunhong Yao have contributed equally to this work.

Authors and Affiliations

  1. Pathology Department of The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523713, China

    Duo Peng, Yan Wang, Yunhong Yao, Xinrong Hu & Yi Zhao

  2. Microbiology and Immunology Department, Guangdong Medical University, Dongguan, 523808, China

    Yan Wang & Yi Zhao

  3. Pathology Department, Guangdong Medical University, Dongguan, 523808, China

    Yunhong Yao, Shuang Wu, Kaijing Zeng & Xinrong Hu

  4. School of Medical Technology, Guangdong Medical University, Dongguan, 523808, China

    Duo Peng, Zisha Yang & Yi Zhao

Authors
  1. Duo Peng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yunhong Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Zisha Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shuang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kaijing Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xinrong Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yi Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Yi Zhao and Xinrong Hu led and oversaw the study and provided feedback on the final manuscript. Duo Peng, Yan Wang, and Yunhong Yao conducted the study and drafted the paper. Zisha Yang, Shuang Wu, and Kaijing Zeng assisted with completing the study. All authors have reviewed and approved the final version of the paper.

Corresponding authors

Correspondence to Xinrong Hu or Yi Zhao.

Ethics declarations

Conflict of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethical approval

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

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Peng, D., Wang, Y., Yao, Y. et al. Long-chain polyunsaturated fatty acids influence colorectal cancer progression via the interactions between the intestinal microflora and the macrophages. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-023-04904-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11010-023-04904-y

Keywords

Search

Navigation