Correlation between gut microbiota dysbiosis and colorectal cancer: review
DOI:
https://doi.org/10.12775/QS.2024.22.54326Keywords
gut microbiota, colorectal cancer, dysbiosis, bacteriaAbstract
Introduction and Purpose:
The human gut microbiota, comprising a diverse consortium of approximately 100 trillion microorganisms, is integral to maintaining health and modulating disease processes. Its development begins at birth, influenced by maternal microbiota and environmental factors. Dysbiosis, defined as an imbalance in the gut microbial composition, has been implicated in a range of gastrointestinal pathologies, including colorectal cancer (CRC). This review endeavors to elucidate the relationship between gut microbiota and CRC, examining the impact of specific bacterial taxa on the pathogenesis CRC.
Description of the State of Knowledge:
Gut microbiota encompasses a multitude of microbial species, with their composition differing along the gastrointestinal tract. Healthy gut microbiota perform essential functions such as pathogen protection, metabolic processes, and immune system modulation. Factors like diet and genetics significantly influence microbial composition. Dysbiosis contributes to CRC through inflammation, genotoxin production, and immune modulation. Specific bacteria, such as Fusobacterium nucleatum and Bacteroides fragilis, are associated with CRC. Mechanisms of carcinogenesis include bacterial adherence, invasion of epithelial cells, and activation of pro-inflammatory pathways.
Summary:
Understanding the gut microbiota's role in CRC highlights the importance of maintaining a balanced microbiome for cancer prevention. Dietary interventions promoting beneficial bacteria and reducing harmful species could mitigate CRC risk. Further research should prioritize the identification of microbial biomarkers for early CRC detection and the development of therapeutic strategies aimed at modulating the gut microbiota. These efforts will enhance CRC prevention and treatment modalities.
References
Kc D, Sumner R, Lippmann S. Gut microbiota and health. Postgrad Med. 2020 Apr;132(3):274. https://doi.org/10.1080/00325481.2019.1662711
Gomaa EZ. Human gut microbiota/microbiome in health and diseases: a review. Antonie Van Leeuwenhoek. 2020 Dec;113(12):2019-2040. https://doi.org/10.1007/s10482-020-01474-7
Dominguez-Bello MG, Blaser MJ, Ley RE, Knight R. Development of the human gastrointestinal microbiota and insights from high-throughput sequencing. Gastroenterology. 2011 May;140(6):1713-9. https://doi.org/10.1053/j.gastro.2011.02.011
Adak A, Khan MR. An insight into gut microbiota and its functionalities. Cell Mol Life Sci. 2019 Feb;76(3):473-493. https://doi.org/10.1007/s00018-018-2943-4
Roy Sarkar S, Banerjee S. Gut microbiota in neurodegenerative disorders. J Neuroimmunol. 2019 Mar 15;328:98-104. https://doi.org/10.1016/j.jneuroim.2019.01.004
Joshi D, Roy S, Banerjee S. Prebiotics: a functional food in health and disease. S.C. Mandal, V. Mandal, T. Konishi (Eds.), Natural Products & Drug Discovery, Elsevier, Amsterdam (2018), pp. 507-523
Nishida A, Inoue R, Inatomi O, et al. Gut microbiota in the pathogenesis of inflammatory bowel disease. Clin J Gastroenterol. 2018 Feb;11(1):1-10. https://doi.org/10.1007/s12328-017-0813-5
Dekker E, Tanis PJ, Vleugels JLA, et al. Colorectal cancer. Lancet. 2019 Oct 19;394(10207):1467-1480. https://doi.org/10.1016/S0140-6736(19)32319-0
Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 Apr 4. https://doi.org/10.3322/caac.21834
Henrikson NB, Webber EM, Goddard KA, et al. Family history and the natural history of colorectal cancer: systematic review. Genet Med. 2015 Sep;17(9):702-12. https://doi.org/10.1038/gim.2014.188
Czene K, Lichtenstein P, Hemminki K. Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish Family-Cancer Database. Int J Cancer. 2002 May 10;99(2):260-6. https://doi.org/10.1002/ijc.10332
Kyrgiou M, Kalliala I, Markozannes G, et al. Adiposity and cancer at major anatomical sites: umbrella review of the literature. BMJ. 2017 Feb 28;356:j477. https://doi.org/10.1136/bmj.j477
World Cancer Research Fund/American Institute for Cancer Research. The Continuous Update Project Expert Report 2018. Diet, Nutrition, Physical Activity and Cancer: colorectal cancer. World Cancer Research Fund Network; 2018. Accessed May 23, 2024. https://www.wcrf.org/sites/default/files/Colorectal-cancer-report.pdf
Nakatsu G, Li X, Zhou H, Sheng J, Wong SH, Wu WK, Ng SC, Tsoi H, Dong Y, Zhang N, He Y, Kang Q, Cao L, Wang K, Zhang J, Liang Q, Yu J, Sung JJ. Gut mucosal microbiome across stages of colorectal carcinogenesis. Nat Commun. 2015 Oct 30;6:8727. https://doi.org/10.1038/ncomms9727
Kwong TNY, Wang X, Nakatsu G, Chow TC, Tipoe T, Dai RZW, Tsoi KKK, Wong MCS, Tse G, Chan MTV, Chan FKL, Ng SC, Wu JCY, Wu WKK, Yu J, Sung JJY, Wong SH. Association Between Bacteremia From Specific Microbes and Subsequent Diagnosis of Colorectal Cancer. Gastroenterology. 2018 Aug;155(2):383-390.e8. https://doi.org/10.1053/j.gastro.2018.04.028
Robles-Alonso V, Guarner F. Progreso en el conocimiento de la microbiota intestinal humana [Progress in the knowledge of the intestinal human microbiota]. Nutr Hosp. 2013 May-Jun;28(3):553-7. Spanish. https://doi.org/10.3305/nh.2013.28.3.6601
Qin J, Li R, Raes J, Arumugam M, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010 Mar 4;464(7285):59-65. https://doi.org/10.1038/nature08821
Bäckhed F, Roswall J, Peng Y, et al. Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. Cell Host Microbe. 2015 May 13;17(5):690-703. https://doi.org/10.1016/j.chom.2015.04.004
Jethwani P, Grover K. Gut microbiota in health and diseases—a review. Int J Curr Microbiol Appl Sci. 2019; 8(8):1586–1599. https://doi.org/10.20546/ijcmas.2019.808.187
Lagier JC, Khelaifia S, Alou MT, et al. Culture of previously uncultured members of the human gut microbiota by culturomics. Nat Microbiol. 2016 Nov 7;1:16203. https://doi.org/10.1038/nmicrobiol.2016.203
Kazor CE, Mitchell PM, Lee AM, et al. Diversity of bacterial populations on the tongue dorsa of patients with halitosis and healthy patients. J Clin Microbiol. 2003 Feb;41(2):558-63. https://doi.org/10.1128/JCM.41.2.558-563.2003
Reed PI, Smith PL, Haines K, House FR, Walters CL. Gastric juice N-nitrosamines in health and gastroduodenal disease. Lancet. 1981 Sep 12;2(8246):550-2. https://doi.org/10.1016/s0140-6736(81)90939-9
Nardone G, Compare D. The human gastric microbiota: Is it time to rethink the pathogenesis of stomach diseases? United European Gastroenterol J. 2015 Jun;3(3):255-60. https://doi.org/10.1177/2050640614566846
El Aidy S, van den Bogert B, Kleerebezem M. The small intestine microbiota, nutritional modulation and relevance for health. Curr Opin Biotechnol. 2015 Apr;32:14-20. https://doi.org/10.1016/j.copbio.2014.09.005
Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA. Diversity of the human intestinal microbial flora. Science. 2005 Jun 10;308(5728):1635-8. https://doi.org/10.1126/science.1110591
Mariat D, Firmesse O, Levenez F, Guimarăes V, Sokol H, Doré J, Corthier G, Furet JP. The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol. 2009 Jun 9;9:123. https://doi.org/10.1186/1471-2180-9-123
Hollister EB, Gao C, Versalovic J. Compositional and functional features of the gastrointestinal microbiome and their effects on human health. Gastroenterology. 2014 May;146(6):1449-58. https://doi.org/10.1053/j.gastro.2014.01.052
Mills S, Stanton C, Lane JA, Smith GJ, Ross RP. Precision Nutrition and the Microbiome, Part I: Current State of the Science. Nutrients. 2019 Apr 24;11(4):923. https://doi.org/10.3390/nu11040923
Rothschild D, Weissbrod O, Barkan E, et al. Environment dominates over host genetics in shaping human gut microbiota. Nature. 2018 Mar 8;555(7695):210-215. https://doi.org/10.1038/nature25973
Louis P, Flint HJ. Formation of propionate and butyrate by the human colonic microbiota. Environ Microbiol. 2017 Jan;19(1):29-41. https://doi.org/10.1111/1462-2920.13589
Wiley NC, Dinan TG, Ross RP, et al. The microbiota-gut-brain axis as a key regulator of neural function and the stress response: Implications for human and animal health. J Anim Sci. 2017 Jul;95(7):3225-3246. https://doi.org/10.2527/jas.2016.1256
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 May 13;17(5):662-71. https://doi.org/10.1016/j.chom.2015.03.005
Riquelme E, Zhang Y, Zhang L, et al. Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes. Cell. 2019 Aug 8;178(4):795-806.e12. https://doi.org/10.1016/j.cell.2019.07.008
Pushalkar S, Hundeyin M, Daley D, et al. The Pancreatic Cancer Microbiome Promotes Oncogenesis by Induction of Innate and Adaptive Immune Suppression. Cancer Discov. 2018 Apr;8(4):403-416. https://doi.org/10.1158/2159-8290.CD-17-1134
Zheng P, Zeng B, Liu M, et al. The gut microbiome from patients with schizophrenia modulates the glutamate-glutamine-GABA cycle and schizophrenia-relevant behaviors in mice. Sci Adv. 2019 Feb 6;5(2):eaau8317. https://doi.org/10.1126/sciadv.aau8317
Hills RD Jr, Pontefract BA, Mishcon HR, et al. Gut Microbiome: Profound Implications for Diet and Disease. Nutrients. 2019 Jul 16;11(7):1613. https://doi.org/10.3390/nu11071613
Thompson AL, Monteagudo-Mera A, Cadenas MB, Lampl ML, Azcarate-Peril MA. Milk- and solid-feeding practices and daycare attendance are associated with differences in bacterial diversity, predominant communities, and metabolic and immune function of the infant gut microbiome. Front Cell Infect Microbiol. 2015 Feb 5;5:3. https://doi.org/10.3389/fcimb.2015.00003
Azad MB, Konya T, Maughan H, et al. CHILD Study Investigators. Gut microbiota of healthy Canadian infants: profiles by mode of delivery and infant diet at 4 months. CMAJ. 2013 Mar 19;185(5):385-94. https://doi.org/10.1503/cmaj.121189
Erridge C, Attina T, Spickett CM, Webb DJ. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation. Am J Clin Nutr. 2007 Nov;86(5):1286-92. https://doi.org/10.1093/ajcn/86.5.1286
Singh RK, Chang HW, Yan D, et al. Influence of diet on the gut microbiome and implications for human health. J Transl Med. 2017 Apr 8;15(1):73. https://doi.org/10.1186/s12967-017-1175-y
Cani PD, Amar J, Iglesias MA, et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes. 2007 Jul;56(7):1761-72. https://doi.org/10.2337/db06-1491
Zhang C, Zhang M, Wang S, et al. Interactions between gut microbiota, host genetics and diet relevant to development of metabolic syndromes in mice. ISME J. 2010 Feb;4(2):232-41. https://doi.org/10.1038/ismej.2009.112
Singh RP, Halaka DA, Hayouka Z, Tirosh O. High-Fat Diet Induced Alteration of Mice Microbiota and the Functional Ability to Utilize Fructooligosaccharide for Ethanol Production. Front Cell Infect Microbiol. 2020 Aug 7;10:376. https://doi.org/10.3389/fcimb.2020.00376
Ghoshal S, Witta J, Zhong J, de Villiers W, Eckhardt E. Chylomicrons promote intestinal absorption of lipopolysaccharides. J Lipid Res. 2009 Jan;50(1):90-7. https://doi.org/10.1194/jlr.M800156-JLR200
Tomova A, Bukovsky I, Rembert E, et al. The Effects of Vegetarian and Vegan Diets on Gut Microbiota. Front Nutr. 2019 Apr 17;6:47. https://doi.org/10.3389/fnut.2019.00047
De Filippo C, Cavalieri D, Di Paola M, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci U S A. 2010 Aug 17;107(33):14691-6. https://doi.org/10.1073/pnas.1005963107
Wu GD, Chen J, Hoffmann C, Bittinger K, Chen YY, Keilbaugh SA, Bewtra M, Knights D, Walters WA, Knight R, et al. Linking long-term dietary patterns with gut microbial enterotypes. Science. 2011 Oct 7;334(6052):105-8. https://doi.org/10.1126/science.1208344
De Palma G, Nadal I, Collado MC, Sanz Y. Effects of a gluten-free diet on gut microbiota and immune function in healthy adult human subjects. Br J Nutr. 2009 Oct;102(8):1154-60. https://doi.org/10.1017/S0007114509371767
Bonder MJ, Tigchelaar EF, Cai X, et al. The influence of a short-term gluten-free diet on the human gut microbiome. Genome Med. 2016 Apr 21;8(1):45. https://doi.org/10.1186/s13073-016-0295-y
Iebba V, Totino V, Gagliardi A, Santangelo F, Cacciotti F, Trancassini M, Mancini C, Cicerone C, Corazziari E, Pantanella F, Schippa S. Eubiosis and dysbiosis: the two sides of the microbiota. New Microbiol. 2016 Jan;39(1):1-12.
Zoetendal E, Akkermans A, Akkermans-van Vliet W, de Visser J, de Vos W. The host genotype affects the bacterial community in the human gastrointestinal tract. Microbial Ecology in Health and Disease. 2001; 13, 129-134. https://doi.org/10.1080/089106001750462669
Kurilshikov A, Wijmenga C, Fu J, Zhernakova A. Host Genetics and Gut Microbiome: Challenges and Perspectives. Trends Immunol. 2017 Sep;38(9):633-647. https://doi.org/10.1016/j.it.2017.06.003
Richards AL, Burns MB, Alazizi A, Barreiro LB, Pique-Regi R, Blekhman R, Luca F. Genetic and transcriptional analysis of human host response to healthy gut microbiota. mSystems. 2016 Jul-Aug;1(4):e00067-16. https://doi.org/10.1128/mSystems.00067-16
Turpin W, Espin-Garcia O, Xu W, Silverberg MS, Kevans D, Smith MI, Guttman DS, Griffiths A, Panaccione R, Otley A, Xu L, Shestopaloff K, Moreno-Hagelsieb G; GEM Project Research Consortium; Paterson AD, Croitoru K. Association of host genome with intestinal microbial composition in a large healthy cohort. Nat Genet. 2016 Nov;48(11):1413-1417. https://doi.org/10.1038/ng.3693
Wacklin P, Mäkivuokko H, Alakulppi N, Nikkilä J, Tenkanen H, Räbinä J, Partanen J, Aranko K, Mättö J. Secretor genotype (FUT2 gene) is strongly associated with the composition of Bifidobacteria in the human intestine. PLoS One. 2011;6(5):e20113. https://pubmed.ncbi.nlm.nih.gov/21625510/
Chen C, Huang X, Fang S, Yang H, He M, Zhao Y, Huang L. Contribution of Host Genetics to the Variation of Microbial Composition of Cecum Lumen and Feces in Pigs. Front Microbiol. 2018 Oct 31;9:2626. https://doi.org/10.3389/fmicb.2018.02626
Virtue AT, McCright SJ, Wright JM, et al. The gut microbiota regulates white adipose tissue inflammation and obesity via a family of microRNAs. Sci Transl Med. 2019 Jun 12;11(496):eaav1892. https://doi.org/10.1126/scitranslmed.aav1892
Foley KP, Zlitni S, Denou E, Duggan BM, Chan RW, Stearns JC, Schertzer JD. Long term but not short term exposure to obesity related microbiota promotes host insulin resistance. Nat Commun. 2018 Nov 8;9(1):4681. https://doi.org/10.1038/s41467-018-07146-5
Brown K, Godovannyi A, Ma C, et al. Prolonged antibiotic treatment induces a diabetogenic intestinal microbiome that accelerates diabetes in NOD mice. ISME J. 2016 Feb;10(2):321-32. https://doi.org/10.1038/ismej.2015.114
Maini Rekdal V, Bess EN, Bisanz JE, Turnbaugh PJ, Balskus EP. Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism. Science. 2019 Jun 14;364(6445):eaau6323. https://doi.org/10.1126/science.aau6323
Jin C, Lagoudas GK, Zhao C, et al. Commensal Microbiota Promote Lung Cancer Development via γδ T Cells. Cell. 2019 Feb 21;176(5):998-1013.e16. https://doi.org/10.1016/j.cell.2018.12.040
Tilg H, Adolph TE, Gerner RR, Moschen AR. The Intestinal Microbiota in Colorectal Cancer. Cancer Cell. 2018 Jun 11;33(6):954-964. https://doi.org/10.1016/j.ccell.2018.03.004
Polk DB, Peek RM Jr. Helicobacter pylori: gastric cancer and beyond. Nat Rev Cancer. 2010 Jun;10(6):403-14. https://doi.org/10.1038/nrc2857
Wong BC, Lam SK, Wong WM, et al. China Gastric Cancer Study Group. Helicobacter pylori eradication to prevent gastric cancer in a high-risk region of China: a randomized controlled trial. JAMA. 2004 Jan 14;291(2):187-94. https://doi.org/10.1001/jama.291.2.187
Couturier-Maillard A, Secher T, Rehman A,et al. NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J Clin Invest. 2013 Feb;123(2):700-11. https://doi.org/10.1172/JCI62236
Hu B, Elinav E, Huber S, et al. Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9862-7. https://doi.org/10.1073/pnas.1307575110
Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature. 2012 Jun 13;486(7402):207-14. https://doi.org/10.1038/nature11234
Dai Z, Coker OO, Nakatsu G, et al. Multi-cohort analysis of colorectal cancer metagenome identified altered bacteria across populations and universal bacterial markers. Microbiome. 2018 Apr 11;6(1):70. https://doi.org/10.1186/s40168-018-0451-2
Wirbel J, Pyl PT, Kartal E, et al. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat Med. 2019 Apr;25(4):679-689. https://doi.org/10.1038/s41591-019-0406-6
Wang T, Cai G, Qiu Y, et al. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J. 2012 Feb;6(2):320-9. https://doi.org/10.1038/ismej.2011.109
Zumkeller N, Brenner H, Zwahlen M, Rothenbacher D. Helicobacter pylori infection and colorectal cancer risk: a meta-analysis. Helicobacter. 2006 Apr;11(2):75-80. https://doi.org/10.1111/j.1523-5378.2006.00381.x
Mirza NN, McCloud JM, Cheetham MJ. Clostridium septicum sepsis and colorectal cancer - a reminder. World J Surg Oncol. 2009 Oct 6;7:73. https://doi.org/10.1186/1477-7819-7-73
Feng Q, Liang S, Jia H, et al. Gut microbiome development along the colorectal adenoma-carcinoma sequence. Nat Commun. 2015 Mar 11;6:6528. https://doi.org/10.1038/ncomms7528
Yu J, Feng Q, Wong SH, et al. Metagenomic analysis of faecal microbiome as a tool towards targeted non-invasive biomarkers for colorectal cancer. Gut. 2017 Jan;66(1):70-78. https://doi.org/10.1136/gutjnl-2015-309800
Grivennikov SI, Wang K, Mucida D, et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature. 2012 Nov 8;491(7423):254-8. https://doi.org/10.1038/nature11465
Gagnière J, Raisch J, Veziant J, et al. Gut microbiota imbalance and colorectal cancer. World J Gastroenterol. 2016 Jan 14;22(2):501-18. https://doi.org/10.3748/wjg.v22.i2.501
Hold GL. Gastrointestinal Microbiota and Colon Cancer. Dig Dis. 2016;34(3):244-50. https://doi.org/10.1159/000443358
Kostic AD, Gevers D, Pedamallu CS, et al. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 2012 Feb;22(2):292-8. https://doi.org/10.1101/gr.126573.111
McCoy AN, Araújo-Pérez F, Azcárate-Peril A, et al. Fusobacterium is associated with colorectal adenomas. PLoS One. 2013;8(1):e53653. https://doi.org/10.1371/journal.pone.0053653
Rubinstein MR, Wang X, Liu W, et al. Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell Host Microbe. 2013 Aug 14;14(2):195-206. https://doi.org/10.1016/j.chom.2013.07.012
Maddocks OD, Short AJ, Donnenberg MS, et al. Attaching and effacing Escherichia coli downregulate DNA mismatch repair protein in vitro and are associated with colorectal adenocarcinomas in humans. PLoS One. 2009;4(5):e5517. https://doi.org/10.1371/journal.pone.0005517
Prorok-Hamon M, Friswell MK, Alswied A, et al. Colonic mucosa-associated diffusely adherent afaC+ Escherichia coli expressing lpfA and pks are increased in inflammatory bowel disease and colon cancer. Gut. 2014 May;63(5):761-70. https://doi.org/10.1136/gutjnl-2013-304739
Ohnishi N, Yuasa H, Tanaka S, et al. Transgenic expression of Helicobacter pylori CagA induces gastrointestinal and hematopoietic neoplasms in mouse. Proc Natl Acad Sci U S A. 2008 Jan 22;105(3):1003-8. https://doi.org/10.1073/pnas.0711183105
Smith JL, Bayles DO. The contribution of cytolethal distending toxin to bacterial pathogenesis. Crit Rev Microbiol. 2006 Oct-Dec;32(4):227-48. https://doi.org/10.1080/10408410601023557
Ge Z, Schauer DB, Fox JG. In vivo virulence properties of bacterial cytolethal-distending toxin. Cell Microbiol. 2008 Aug;10(8):1599-607. https://doi.org/10.1111/j.1462-5822.2008.01173.x
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Zuzanna Chilimoniuk, Dominik Dudziński, Aleksandra Borkowska, Aleksandra Chałupnik, Piotr Więsyk, Beata Chilimoniuk, Łukasz Gawłowicz, Filip Grzegorzak, Katarzyna Stasiak

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Stats
Number of views and downloads: 174
Number of citations: 0