Exploring the Gut Microbiome's Influence on Colorectal Cancer Development and Management: A Review of Current Knowledge and Future Directions
DOI:
https://doi.org/10.12775/JEHS.2024.70.55587%20Keywords
gut microbiota, colorectal cancer, microbial diversity, inflammatory responses, precision medicineAbstract
Introduction
Colorectal cancer (CRC) is a significant global health concern, ranking as the third most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide, with over 1.9 million new cases and nearly 935,000 deaths annually. The rise in CRC incidence is attributed to various lifestyle changes, including dietary shifts, sedentary behavior, and increased obesity rates. These factors underscore the urgent need for new preventive strategies targeting the underlying mechanisms of CRC development.
Purpose
This review evaluates the intricate relationship between the gut microbiome and CRC, aiming to enhance our understanding of how microbial diversity and composition contribute to CRC pathogenesis.
State of Knowledge
Studies reveal a correlation between the onset and progression of CRC and changes in microbial diversity and specific taxa. In CRC patients, the presence of Fusobacterium nucleatum is linked to inflammation and poor prognosis, while Bacteroides fragilis is associated with promoting colitis and carcinogenesis. The Human Microbiome Project's findings reveal that unique microbial communities can impact inflammation and tumor growth. Meta-analyses underline the crucial role of microbial diversity, influenced by diet and health status, in cancer prevention and progression, particularly in CRC.
Conclusions
Understanding the interactions between the microbiome, diet, and host health is crucial for developing targeted treatment strategies and precision diagnostics for CRC. Insights from microbiome research could significantly improve patient outcomes in CRC management. Further high-quality studies are essential to fully elucidate the therapeutic potential of the microbiome in CRC treatment.
References
Turnbaugh PJ, Ley RE, Hamady M, et al. The human microbiome project. Nature. 2007;449(7164):804-810. doi:10.1038/nature06244.
Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486(7402):207-214. doi:10.1038/nature11234.
Gilbert JA, Quinn RA, Debelius J, et al. Microbiome-wide association studies link dynamic microbial consortia to disease. Nature. 2016;535(7610):94-103. doi:10.1038/nature18850.
Baxter NT, Zackular JP, Chen GY, Schloss PD. Structure of the gut microbiome following colonization with human feces determines colonic tumor burden. Microbiome. 2014;2:20. doi:10.1186/2049-2618-2-20.
Koyande N, Gangopadhyay M, Thatikonda S, Rengan AK. The role of gut microbiota in the development of colorectal cancer: a review. Int J Colorectal Dis. 2022;37(7):1509-1523. doi:10.1007/s00384-022-04192-w.
Chen H, Jiao J, Wei M, et al. Metagenomic analysis of the interaction between the gut microbiota and colorectal cancer: a paired-sample study based on the GMrepo database. Gut Pathog. 2022;14(1):48. doi:10.1186/s13099-022-00527-8.
Zhang HP, Li SY, Wang JP, Lin J. Clinical significance and biological roles of cyclins in gastric cancer. Onco Targets Ther. 2018;11:6673-6685. doi:10.2147/OTT.S171716.
Li P, Gao L, Cui T, Zhang W, Zhao Z, Chen L. Cops5 safeguards genomic stability of embryonic stem cells through regulating cellular metabolism and DNA repair. Proc Natl Acad Sci U S A. 2020;117(5):2519-2525. doi:10.1073/pnas.1915079117.
Anderson SM, Sears CL. The Role of the Gut Microbiome in Cancer: A Review, With Special Focus on Colorectal Neoplasia and Clostridioides difficile. Clin Infect Dis. 2023;77(Suppl 6)
. doi:10.1093/cid/ciad640.
Steele CC, Pirkle JRA, Davis IR, Kirkpatrick K. Dietary effects on the determinants of food choice: Impulsive choice, discrimination, incentive motivation, preference, and liking in male rats. Appetite. 2019;136:160-172. doi:10.1016/j.appet.2019.01.023.
Williamson AJ, Jacobson R, van Praagh JB, et al. Enterococcus faecalis promotes a migratory and invasive phenotype in colon cancer cells. Neoplasia. 2022;27:100787. doi:10.1016/j.neo.2022.100787
Siddiqui R, Boghossian A, Alharbi AM, Alfahemi H, Khan NA. The Pivotal Role of the Gut Microbiome in Colorectal Cancer. Biology (Basel). 2022;11(11):1642. Published 2022 Nov 9. doi:10.3390/biology11111642
Brennan CA, Clay SL, Lavoie SL, et al. Fusobacterium nucleatum drives a pro-inflammatory intestinal microenvironment through metabolite receptor-dependent modulation of IL-17 expression. Gut Microbes. 2021;13(1):1987780. doi:10.1080/19490976.2021.1987780
Zhu Y, Li X. Advances of Wnt Signalling Pathway in Colorectal Cancer. Cells. 2023;12(3):447. Published 2023 Jan 30. doi:10.3390/cells12030447
He K, Gan WJ. Wnt/β-Catenin Signaling Pathway in the Development and Progression of Colorectal Cancer. Cancer Manag Res. 2023;15:435-448. Published 2023 May 23. doi:10.2147/CMAR.S411168
Cheng WT, Kantilal HK, Davamani F. The Mechanism of Bacteroides fragilis Toxin Contributes to Colon Cancer Formation. Malays J Med Sci. 2020;27(4):9-21. doi:10.21315/mjms2020.27.4.2
Dai Z, Zhang J, Wu Q, et al. The role of microbiota in the development of colorectal cancer. Int J Cancer. 2019;145(8):2032-2041. doi:10.1002/ijc.32017
Lawrence T. The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol. 2009;1(6):a001651. doi:10.1101/cshperspect.a001651
Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2:17023-. doi:10.1038/sigtrans.2017.23
Hou X, Zheng Z, Wei J, Zhao L. Effects of gut microbiota on immune responses and immunotherapy in colorectal cancer. Front Immunol. 2022;13:1030745. Published 2022 Nov 8. doi:10.3389/fimmu.2022.1030745
Roy R, Singh SK. The Microbiome Modulates the Immune System to Influence Cancer Therapy. Cancers (Basel). 2024;16(4):779. Published 2024 Feb 14. doi:10.3390/cancers16040779
Tojjari A, Abushukair H, Saeed A. The Crosstalk between Microbiome and Immunotherapeutics: Myth or Reality. Cancers (Basel). 2022;14(19):4641. Published 2022 Sep 24. doi:10.3390/cancers14194641
Genua F, Raghunathan V, Jenab M, Gallagher WM, Hughes DJ. The Role of Gut Barrier Dysfunction and Microbiome Dysbiosis in Colorectal Cancer Development. Front Oncol. 2021;11:626349. Published 2021 Apr 15. doi:10.3389/fonc.2021.626349
Martin-Gallausiaux C, Marinelli L, Blottière HM, Larraufie P, Lapaque N. SCFA: mechanisms and functional importance in the gut. Proc Nutr Soc. 2021;80(1):37-49. doi:10.1017/S0029665120006916
Cheng WT, Kantilal HK, Davamani F. The Mechanism of Bacteroides fragilis Toxin Contributes to Colon Cancer Formation. Malays J Med Sci. 2020;27(4):9-21. doi:10.21315/mjms2020.27.4.2
Quaglio AEV, Grillo TG, De Oliveira ECS, Di Stasi LC, Sassaki LY. Gut microbiota, inflammatory bowel disease and colorectal cancer. World J Gastroenterol. 2022;28(30):4053-4060. doi:10.3748/wjg.v28.i30.4053
Ranjbar M, Salehi R, Haghjooy Javanmard S, et al. The dysbiosis signature of Fusobacterium nucleatum in colorectal cancer-cause or consequences? A systematic review [published correction appears in Cancer Cell Int. 2022 Mar 26;22(1):134. doi: 10.1186/s12935-022-02549-3]. Cancer Cell Int. 2021;21(1):194. Published 2021 Apr 6. doi:10.1186/s12935-021-01886-z
Slavin J. Fiber and prebiotics: mechanisms and health benefits. Nutrients. 2013;5(4):1417-1435. Published 2013 Apr 22. doi:10.3390/nu5041417
Veettil SK, Teerawattanapong N, Ching SM, et al. Effects of chemopreventive agents on the incidence of recurrent colorectal adenomas: a systematic review with network meta-analysis of randomized controlled trials. Onco Targets Ther. 2017;10:2689-2700. Published 2017 May 23. doi:10.2147/OTT.S127335
Jadhav A, Jagtap S, Vyavahare S, Sharbidre A, Kunchiraman B. Reviewing the potential of probiotics, prebiotics and synbiotics: advancements in treatment of ulcerative colitis. Front Cell Infect Microbiol. 2023;13:1268041. Published 2023 Dec 8. doi:10.3389/fcimb.2023.1268041
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. Published 2011 Nov 10. doi:10.1136/bmj.d6617
Gómez-Pinilla F. Brain foods: the effects of nutrients on brain function. Nat Rev Neurosci. 2008;9(7):568-578. doi:10.1038/nrn2421
Leeuwendaal NK, Stanton C, O'Toole PW, Beresford TP. Fermented Foods, Health and the Gut Microbiome. Nutrients. 2022;14(7):1527. Published 2022 Apr 6. doi:10.3390/nu14071527
Biazzo M, Deidda G. Fecal Microbiota Transplantation as New Therapeutic Avenue for Human Diseases. J Clin Med. 2022;11(14):4119. Published 2022 Jul 15. doi:10.3390/jcm11144119
Behrouzi A, Nafari AH, Siadat SD. The significance of microbiome in personalized medicine. Clin Transl Med. 2019;8(1):16. Published 2019 May 13. doi:10.1186/s40169-019-0232-y
Dikeocha IJ, Al-Kabsi AM, Eid EEM, Hussin S, Alshawsh MA. Probiotics supplementation in patients with colorectal cancer: a systematic review of randomized controlled trials. Nutr Rev. 2021;80(1):22-49. doi:10.1093/nutrit/nuab006
Zhen J, Liu C, Liao F, Zhang J, Xie H, Tan C, Dong W. The global research of microbiota in colorectal cancer screening: a bibliometric and visualization analysis. Front Oncol. 2023 May 5;13:1169369. doi: 10.3389/fonc.2023.1169369. PMID: 37213286; PMCID: PMC10196493.
John Kenneth M, Tsai HC, Fang CY, Hussain B, Chiu YC, Hsu BM. Diet-mediated gut microbial community modulation and signature metabolites as potential biomarkers for early diagnosis, prognosis, prevention and stage-specific treatment of colorectal cancer. J Adv Res. 2023;52:45-57. doi:10.1016/j.jare.2022.12.015
Fong W, Li Q, Yu J. Gut microbiota modulation: a novel strategy for prevention and treatment of colorectal cancer. Oncogene. 2020;39(26):4925-4943. doi:10.1038/s41388-020-1341-1
Behrouzi A, Nafari AH, Siadat SD. The significance of microbiome in personalized medicine. Clin Transl Med. 2019;8(1):16. Published 2019 May 13. doi:10.1186/s40169-019-0232-y
Aggarwal N, Kitano S, Puah GRY, Kittelmann S, Hwang IY, Chang MW. Microbiome and Human Health: Current Understanding, Engineering, and Enabling Technologies. Chem Rev. 2023;123(1):31-72. doi:10.1021/acs.chemrev.2c00431
Ulger Y, Delik A, Akkız H. Gut Microbiome and colorectal cancer: discovery of bacterial changes with metagenomics application in Turkısh population. Genes Genomics. 2024;46(9):1059-1070. doi:10.1007/s13258-024-01538-2
Wong SH, Yu J. Gut microbiota in colorectal cancer: mechanisms of action and clinical applications. Nat Rev Gastroenterol Hepatol. 2019;16(11):690-704. doi:10.1038/s41575-019-0209-8
Zwezerijnen-Jiwa FH, Sivov H, Paizs P, Zafeiropoulou K, Kinross J. A systematic review of microbiome-derived biomarkers for early colorectal cancer detection. Neoplasia. 2023;36:100868. doi:10.1016/j.neo.2022.100868
Liu Y, Lau HC, Yu J. Microbial metabolites in colorectal tumorigenesis and cancer therapy. Gut Microbes. 2023;15(1):2203968. doi:10.1080/19490976.2023.2203968
Jiang S, Ma W, Ma C, Zhang Z, Zhang W, Zhang J. An emerging strategy: probiotics enhance the effectiveness of tumor immunotherapy via mediating the gut microbiome. Gut Microbes. 2024;16(1):2341717. doi:10.1080/19490976.2024.2341717
Kang X, Lau HC, Yu J. Modulating gut microbiome in cancer immunotherapy: Harnessing microbes to enhance treatment efficacy. Cell Rep Med. 2024;5(4):101478. doi:10.1016/j.xcrm.2024.101478
Yu T, Guo F, Yu Y, et al. Fusobacterium nucleatum Promotes Chemoresistance to Colorectal Cancer by Modulating Autophagy. Cell. 2017;170(3):548-563.e16. doi:10.1016/j.cell.2017.07.008
Kvakova M, Kamlarova A, Stofilova J, Benetinova V, Bertkova I. Probiotics and postbiotics in colorectal cancer: Prevention and complementary therapy. World J Gastroenterol. 2022;28(27):3370-3382. doi:10.3748/wjg.v28.i27.3370
Khavandegar A, Heidarzadeh A, Angoorani P, et al. Adherence to the Mediterranean diet can beneficially affect the gut microbiota composition: a systematic review. BMC Med Genomics. 2024;17(1):91. Published 2024 Apr 17. doi:10.1186/s12920-024-01861-3
Loke YL, Chew MT, Ngeow YF, Lim WWD, Peh SC. Colon Carcinogenesis: The Interplay Between Diet and Gut Microbiota. Front Cell Infect Microbiol. 2020;10:603086. Published 2020 Dec 8. doi:10.3389/fcimb.2020.603086
Cronin P, Joyce SA, O'Toole PW, O'Connor EM. Dietary Fibre Modulates the Gut Microbiota. Nutrients. 2021;13(5):1655. Published 2021 May 13. doi:10.3390/nu13051655
Ali N, Vora C, Mathuria A, Kataria N, Mani I. Advances in CRISPR-Cas systems for gut microbiome. Prog Mol Biol Transl Sci. 2024;208:59-81. doi:10.1016/bs.pmbts.2024.07.008
Lerner A, Benzvi C, Vojdani A. The Potential Harmful Effects of Genetically Engineered Microorganisms (GEMs) on the Intestinal Microbiome and Public Health. Microorganisms. 2024;12(2):238. Published 2024 Jan 23. doi:10.3390/microorganisms12020238
O'Doherty KC, Virani A, Wilcox ES. The Human Microbiome and Public Health: Social and Ethical Considerations. Am J Public Health. 2016;106(3):414-420. doi:10.2105/AJPH.2015.302989
Amato KR, Arrieta MC, Azad MB, et al. The human gut microbiome and health inequities. Proc Natl Acad Sci U S A. 2021;118(25):e2017947118. doi:10.1073/pnas.2017947118
Sawicki T, Ruszkowska M, Danielewicz A, Niedźwiedzka E, Arłukowicz T, Przybyłowicz KE. A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis. Cancers (Basel). 2021;13(9):2025. Published 2021 Apr 22. doi:10.3390/cancers13092025
Tortora SC, Bodiwala VM, Quinn A, Martello LA, Vignesh S. Microbiome and colorectal carcinogenesis: Linked mechanisms and racial differences. World J Gastrointest Oncol. 2022;14(2):375-395. doi:10.4251/wjgo.v14.i2.375
Herlo LF, Salcudean A, Sirli R, et al. Gut Microbiota Signatures in Colorectal Cancer as a Potential Diagnostic Biomarker in the Future: A Systematic Review. Int J Mol Sci. 2024;25(14):7937. Published 2024 Jul 20. doi:10.3390/ijms25147937
Ma T, Tu K, Ou Q, Fang Y, Zhang C. Comparing the Associations of Dietary Patterns Identified through Principal Component Analysis and Cluster Analysis with Colorectal Cancer Risk: A Large Case-Control Study in China. Nutrients. 2023;16(1):147. Published 2023 Dec 31. doi:10.3390/nu16010147
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Copyright (c) 2024 Wiktor Grela, Jagoda Niewiadomska, Daria Furtak, Dawid Tulej, Paulina Głogowska, Alicja Dziedzic, Natalia Gniaź, Dominika Marciniuk, Natalia Marko, Aleksandra Górska

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