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Review

The roles of microbial products in the development of colorectal cancer: a review

, , , , , , , , & show all
Pages 720-735 | Received 09 Dec 2020, Accepted 08 Feb 2021, Published online: 22 Feb 2021

References

  • Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.. CA Cancer J Clin. 2018;68(6):394–424.
  • Xu K, Jiang B. Analysis of mucosa-associated microbiota in colorectal cancer. Med Sci Monit. 2017;23:4422–4430.
  • 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;66(1):70–78.
  • Dang AT, Marsland BJ. Microbes, metabolites, and the gut–lung axis. Mucosal Immunol. 2019;12(4):843–850.
  • Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 2016;14(8):e1002533.
  • Ringel Y, Maharshak N, Ringel-Kulka T, et al. High throughput sequencing reveals distinct microbial populations within the mucosal and luminal niches in healthy individuals. Gut Microbes. 2015;6(3):173–181.
  • Morgillo F, Dallio M, Della Corte CM, et al. Carcinogenesis as a result of multiple inflammatory and oxidative hits: a comprehensive review from tumor microenvironment to gut microbiota. Neoplasia. 2018;20(7):721–733.
  • Shukla SD, Budden KF, Neal R, et al. Microbiome effects on immunity, health and disease in the lung. Clin Transl Immunology. 2017;6(3):e133.
  • Feng Q, Chen W-D, Wang Y-D. Gut microbiota: an integral moderator in health and disease. Front Microbiol. 2018;9:151.
  • 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.
  • Guo -F-F, Yu T-C, Hong J, et al. Emerging roles of hydrogen sulfide in inflammatory and neoplastic colonic diseases. Front Physiol. 2016;7:156.
  • Wu X, Wu Y, He L, et al. Effects of the intestinal microbial metabolite butyrate on the development of colorectal cancer. J Cancer. 2018;9(14):2510–2517.
  • O’Keefe SJD. Diet, microorganisms and their metabolites, and colon cancer. Nature Reviews Gastroenterology & Hepatology. 2016;13(12):691–706.
  • van de Wouw M, Boehme M, Lyte JM, et al. Short-chain fatty acids: microbial metabolites that alleviate stress-induced brain-gut axis alterations. J Physiol. 2018;596(20):4923–4944.
  • Wang G, Yu Y, Wang Y-Z, et al. Role of SCFAs in gut microbiome and glycolysis for colorectal cancer therapy. J Cell Physiol. 2019;234(10):17023–17049.
  • Yusuf F, Adewiah S, Fatchiyah F. The level short chain fatty acids and HSP 70 in colorectal cancer and non-colorectal cancer. Acta informatica medica: AIM: journal of the Society for Medical Informatics of Bosnia & Herzegovina: casopis Drustva za medicinsku informatiku BiH. 2018;26:160–163.
  • Louis P, Flint HJ. Formation of propionate and butyrate by the human colonic microbiota. Environ Microbiol. 2017;19(1):29–41.
  • Medina V, Edmonds B, Young GP, et al. Induction of caspase-3 protease activity and apoptosis by butyrate and trichostatin A (inhibitors of histone deacetylase): dependence on protein synthesis and synergy with a mitochondrial/cytochrome c-dependent pathway.. Cancer Res. 1997;57(17):3697–3707.
  • Koppenol WH, Bounds PL, Dang CV. Otto Warburg’s contributions to current concepts of cancer metabolism. Nature Reviews Cancer. 2011;11(5):325–337.
  • Eslami M, Sadrifar S, Karbalaei M, et al. Importance of the microbiota inhibitory mechanism on the warburg effect in colorectal cancer cells. J Gastrointest Cancer. 2020;51(3):738–747.
  • Astbury SM, Corfe BM. Uptake and metabolism of the short-chain fatty acid butyrate, a critical review of the literature. <![CDATA[Current Drug Metabolism]]>. 2012;13(6):815–821.
  • Han A, Bennett N, Ahmed B, et al. Butyrate decreases its own oxidation in colorectal cancer cells through inhibition of histone deacetylases. Oncotarget. 2018;9(43):27280–27292.
  • Dashwood RH, Myzak MC, Ho E. Dietary HDAC inhibitors: time to rethink weak ligands in cancer chemoprevention? Carcinogenesis. 2006;27(2):344–349.
  • Zhang G, Zhou H, Xiao H, et al. MicroRNA-92a functions as an oncogene in colorectal cancer by targeting PTEN. Dig Dis Sci. 2014;59(1):98–107.
  • Lv H, Zhang Z, Wang Y, et al. MicroRNA-92a promotes colorectal cancer cell growth and migration by inhibiting KLF4. Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics. 2016;23(6):283–290. .
  • Tsuchida A, Ohno S, Wu W, et al. miR-92 is a key oncogenic component of the miR-17-92 cluster in colon cancer. Cancer Sci. 2011;102(12):2264–2271.
  • Milella M, Falcone I, Conciatori F, et al. PTEN: multiple functions in human malignant tumors. Front Oncol. 2015;5:24.
  • Molinari F, Frattini M. Functions and Regulation of the PTEN Gene in Colorectal Cancer.. Front Oncol. 2013;3:326.
  • Hu S, Liu L, Chang EB, et al. Butyrate inhibits pro-proliferative miR-92a by diminishing c-Myc-induced miR-17-92a cluster transcription in human colon cancer cells. Mol Cancer. 2015;14(1):180.
  • Li Q, Ding C, Meng T, et al. Butyrate suppresses motility of colorectal cancer cells via deactivating Akt/ERK signaling in histone deacetylase dependent manner. J Pharmacol Sci. 2017;135(4):148–155.
  • Chiang Y, Song Y, Wang Z, et al. Aberrant expression of miR-203 and its clinical significance in gastric and colorectal cancers. J Gastrointest Surg. 2011;15(1):63–70.
  • Castosa R, Martinez-Iglesias O, Roca-Lema D, et al. Hakai overexpression effectively induces tumour progression and metastasis in vivo. Sci Rep. 2018;8(1):3466.
  • Meng H, Wu J, Huang Q, et al. NEDD9 promotes invasion and migration of colorectal cancer cell line HCT116 via JNK/EMT.. Oncol Lett. 2019;18(4):4022–4029.
  • Han R, Sun Q, Wu J, et al. Sodium butyrate upregulates miR-203 expression to exert anti-proliferation effect on colorectal cancer cells. Cell Physiol Biochem. 2016;39(5):1919–1929.
  • Deng B, Wang B, Fang J, et al. MiRNA-203 suppresses cell proliferation, migration and invasion in colorectal cancer via targeting of EIF5A2. Sci Rep. 2016;6(1):28301.
  • Jan G, Belzacq A-S, Haouzi D, et al. Propionibacteria induce apoptosis of colorectal carcinoma cells via short-chain fatty acids acting on mitochondria. Cell Death Differ. 2002;9(2):179–188.
  • Lan A, Lagadic-Gossmann D, Lemaire C, et al. Acidic extracellular pH shifts colorectal cancer cell death from apoptosis to necrosis upon exposure to propionate and acetate, major end-products of the human probiotic propionibacteria. Apoptosis. 2007;12(3):573–591.
  • Ferro S, Azevedo-Silva J, Casal M, et al. Characterization of acetate transport in colorectal cancer cells and potential therapeutic implications. Oncotarget. 2016;7(43):70639–70653.
  • Oliveira CS, Pereira H, Alves S, et al. Cathepsin D protects colorectal cancer cells from acetate-induced apoptosis through autophagy-independent degradation of damaged mitochondria. Cell Death Dis. 2015;6(6):e1788.
  • Marques C, Oliveira CSF, Alves S, et al. Acetate-induced apoptosis in colorectal carcinoma cells involves lysosomal membrane permeabilization and cathepsin D release. Cell Death Dis. 2013;4(2):e507.
  • Ryu TY, Kim K, Son M-Y, et al. Downregulation of PRMT1, a histone arginine methyltransferase, by sodium propionate induces cell apoptosis in colon cancer.. Oncol Rep. 2019;41(3):1691–1699.
  • Dawson PA, Karpen SJ. Intestinal transport and metabolism of bile acids. J Lipid Res. 2015;56:1085–1099.
  • Lin C-H, Kohli R. Bile acid metabolism and signaling: potential therapeutic target for nonalcoholic fatty liver disease. Clin Transl Gastroenterol. 2018;9(6):164.
  • Maillette de Buy Wenniger L, Beuers U. Bile salts and cholestasis. Dig Liver Dis. 2010;42(6):409–418.
  • Molinero N, Ruiz L, Sánchez B, et al. Intestinal bacteria interplay with bile and cholesterol metabolism: implications on host physiology. Front Physiol. 2019;10:185.
  • Li T, Chiang JYL, Ma Q. Bile acid signaling in metabolic disease and drug therapy. Pharmacol Rev. 2014;66(4):948–983.
  • Khare S, Mustafi R, Cerda S, et al. Ursodeoxycholic acid suppresses Cox-2 expression in colon cancer: roles of Ras, p38, and CCAAT/enhancer-binding protein. Nutr Cancer. 2008;60(3):389–400.
  • Im E, Martinez JD. Ursodeoxycholic acid (UDCA) can inhibit deoxycholic acid (DCA)-induced apoptosis via modulation of EGFR/Raf-1/ERK signaling in human colon cancer cells. J Nutr. 2004;134(2):483–486.
  • Serfaty L, et al. Ursodeoxycholic acid therapy and the risk of colorectal adenoma in patients with primary biliary cirrhosis: an observational study. Hepatology. 2003;38(1):203–209.
  • Alberts DS, Martínez ME, Hess LM, et al. Phase III trial of ursodeoxycholic acid to prevent colorectal adenoma recurrence. JNCI: Journal of the National Cancer Institute. 2005;97(11):846–853.
  • Ridlon JM, Bajaj JS. The human gut sterolbiome: bile acid-microbiome endocrine aspects and therapeutics. Acta Pharmaceutica Sinica B. 2015;5(2):99–105.
  • Kim E-K, Cho JH, Kim E, et al. Ursodeoxycholic acid inhibits the proliferation of colon cancer cells by regulating oxidative stress and cancer stem-like cell growth. PloS One. 2017;12(7):e0181183.
  • Rigas B, Tsioulias GJ, Allan C, et al. The effect of bile acids and piroxicam on MHC antigen expression in rat colonocytes during colon cancer development.. Immunology. 1994;83(2):319–323.
  • Shah SA, Volkov Y, Arfin Q, et al. Ursodeoxycholic acid inhibits interleukin beta 1 and deoxycholic acid-induced activation of NF-κB and AP-1 in human colon cancer cells. Int J Cancer. 2006;118(3):532–539.
  • Pearson T, Caporaso JG, Yellowhair M, et al. Effects of ursodeoxycholic acid on the gut microbiome and colorectal adenoma development. Cancer Med. 2019;8(2):617–628.
  • Eaton JE, Silveira MG, Pardi DS, et al. High-dose ursodeoxycholic acid is associated with the development of colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis. Am J Gastroenterol. 2011;106(9):1638–1645.
  • Peterson CT, Rodionov DA, Osterman AL, et al. B Vitamins and their role in immune regulation and cancer. Nutrients. 2020;12(11):3380.
  • Zeman M, Vecka M, Perlík F, et al. Pleiotropic effects of niacin: current possibilities for its clinical use. Acta Pharm. 2016;66(4):449–469.
  • Singh N, Gurav A, Sivaprakasam S, et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity. 2014;40(1):128–139.
  • Salem HA, Wadie W. Effect of niacin on inflammation and angiogenesis in a murine model of ulcerative colitis. Sci Rep. 2017;7(1):7139.
  • Li J, Kong D, Wang Q, et al. Niacin ameliorates ulcerative colitis via prostaglandin D 2 -mediated D prostanoid receptor 1 activation. EMBO Mol Med. 2017;9(5):571–588.
  • Kharkar PS. Cancer stem cell (CSC) inhibitors: a review of recent patents (2012-2015). Expert Opin Ther Pat. 2017;27(7):753–761.
  • Sen U, Shenoy PS, Bose B. Opposing effects of low versus high concentrations of water soluble vitamins/dietary ingredients Vitamin C and niacin on colon cancer stem cells (CSCs). Cell Biol Int. 2017;41(10):1127–1145.
  • Bajor A, Gillberg P-G, Abrahamsson H. Bile acids: short and long term effects in the intestine. Scand J Gastroenterol. 2010;45(6):645–664.
  • O’Neill AM, Burrington CM, Gillaspie EA, et al. High-fat Western diet–induced obesity contributes to increased tumor growth in mouse models of human colon cancer. Nutr Res. 2016;36(12):1325–1334.
  • Ajouz H, Mukherji D, Shamseddine A. Secondary bile acids: an underrecognized cause of colon cancer. World J Surg Oncol. 2014;12(1):164.
  • Payne CM. Hydrophobic bile acids, genomic instability, Darwinian selection, and colon carcinogenesis. Clin Exp Gastroenterol. 2008;1:19–47.
  • Ochsenk�hn T, Bayerd�rffer E, Meining A, et al. Colonic mucosal proliferation is related to serum deoxycholic acid levels. Cancer. 1999;85(8):1664–1669. .
  • Nguyen TT, Ung TT, Kim NH, et al. Role of bile acids in colon carcinogenesis. World J Clin Cases. 2018;6(13):577–588.
  • Bernstein H, Bernstein C, Payne CM, et al. Bile acids as endogenous etiologic agents in gastrointestinal cancer. World J Gastroenterol. 2009;15(27):3329–3340.
  • Zhang T, et al. Hsa-miR-875-5p exerts tumor suppressor function through down-regulation of EGFR in colorectal carcinoma (CRC). Oncotarget. 2016;7(42225–42240). DOI:10.18632/oncotarget.9944
  • Kato S, et al. Revisiting epidermal growth factor receptor (EGFR) amplification as a target for anti-EGFR therapy: analysis of cell-Free circulating tumor DNA in patients with advanced malignancies. JCO Precis Oncol. 2019;3. DOI:10.1200/po.18.00180.
  • Zhou S, Li Y, Lu J, et al. Nuclear factor-erythroid 2-related factor 3 (NRF3) is low expressed in colorectal cancer and its down-regulation promotes colorectal cancer malignance through activating EGFR and p38/MAPK.. Am J Cancer Res. 2019;9(3):511–528.
  • Kundu S, Kumar S, Bajaj A. Cross-talk between bile acids and gastrointestinal tract for progression and development of cancer and its therapeutic implications. IUBMB Life. 2015;67(7):514–523.
  • Liang H, Estes MK, Zhang H, et al. Bile acids target proteolipid nano-assemblies of EGFR and phosphatidic acid in the plasma membrane for stimulation of MAPK signaling. PloS One. 2018;13(8):e0198983.
  • Werneburg NW, Yoon J-H, Higuchi H, et al. Bile acids activate EGF receptor via a TGF-α-dependent mechanism in human cholangiocyte cell lines. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2003;285(1):G31–36.
  • Centuori SM, Gomes CJ, Trujillo J, et al. Deoxycholic acid mediates non-canonical EGFR-MAPK activation through the induction of calcium signaling in colon cancer cells. Biochimica Et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 2016;1861(7):663–670.
  • Farhana L, Nangia-Makker P, Arbit E, et al. Bile acid: a potential inducer of colon cancer stem cells. Stem Cell Res Ther. 2016;7(1):181.
  • Ufnal M, Zadlo A, Ostaszewski R. TMAO: a small molecule of great expectations. Nutrition. 2015;31(11–12):1317–1323.
  • Kaysen GA, Johansen KL, Chertow GM, et al. Associations of trimethylamine N-Oxide with nutritional and inflammatory biomarkers and cardiovascular outcomes in patients new to dialysis. Journal of renal nutrition: the official journal of the Council on Renal Nutrition of the National Kidney Foundation. 2015;25(4):351–356.
  • Tang WH, Wang Z, Kennedy DJ, et al. Gut microbiota-dependent trimethylamine N -Oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015;116(3):448–455.
  • Tang WH, Hazen SL. The contributory role of gut microbiota in cardiovascular disease. J Clin Invest. 2014;124(10):4204–4211.
  • Koeth RA, Levison B, Culley M, et al. γ-Butyrobetaine Is a Proatherogenic Intermediate in Gut Microbial Metabolism of L -Carnitine to TMAO. Cell Metab. 2014;20(5):799–812.
  • Bae S, Ulrich CM, Neuhouser ML, et al. Plasma Choline Metabolites and Colorectal Cancer Risk in the Women’s Health Initiative Observational Study. Cancer Res. 2014;74(24):7442–7452.
  • Xu R, Wang Q, Li L. A genome-wide systems analysis reveals strong link between colorectal cancer and trimethylamine N-oxide (TMAO), a gut microbial metabolite of dietary meat and fat. BMC Genomics. 2015;16(Suppl S7):S4.
  • Chan CWH, Law BMH, Waye MMY, et al. Trimethylamine-N-oxide as one hypothetical link for the relationship between intestinal microbiota and cancer - where we are and where shall we go? J Cancer. 2019;10(23):5874–5882.
  • Rohrmann S, Linseisen J, Allenspach M, et al. Plasma concentrations of trimethylamine-N-oxide are directly associated with dairy food consumption and low-grade inflammation in a german adult population. J Nutr. 2016;146(2):283–289.
  • Kimura H. Production and physiological effects of hydrogen sulfide. Antioxid Redox Signal. 2014;20(5):783–793.
  • O’Keefe SJD, Li JV, Lahti L, et al. Fat, fibre and cancer risk in African Americans and rural Africans. Nat Commun. 2015;6(1):6342.
  • Kanazawa K, Konishi F,Mitsuoka T, et al. Factors influencing the development of sigmoid colon cancer. Bacteriologic and biochemical studies. Cancer. 1996;77:1701–1706.
  • Ramasamy S, Singh S, Taniere P, et al. Sulfide-detoxifying enzymes in the human colon are decreased in cancer and upregulated in differentiation. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2006;291(2):G288–296.
  • Carbonero F, Benefiel AC, Alizadeh-Ghamsari AH, et al. Microbial pathways in colonic sulfur metabolism and links with health and disease. Front Physiol. 2012;3:448.
  • Fan X, Jin Y, Chen G, et al. Gut Microbiota dysbiosis drives the development of colorectal cancer. Digestion. 2020;1–8. doi: 10.1159/000508328
  • Attene-Ramos MS, Wagner ED, Gaskins HR, et al. Hydrogen sulfide induces direct radical-associated DNA damage. Mol Cancer Res. 2007;5(5):455–459.
  • Alhinai EA, Walton W, Commane C. The role of the gut microbiota in colorectal cancer causation. Int J Mol Sci. 2019;20(21):5295.
  • Han S, Zhuang J, Wu Y, et al. <p>Progress in Research on Colorectal Cancer-Related Microorganisms and Metabolites. <![cdata[cancer Management and Research]]>. 2020;12:8703–8720.
  • Ijssennagger N, van der Meer R, van Mil SWC. Sulfide as a mucus barrier-breaker in inflammatory bowel disease? Trends Mol Med. 2016;22(3):190–199.
  • Motta J-P, Flannigan KL, Agbor TA, et al. Hydrogen sulfide protects from colitis and restores intestinal microbiota biofilm and mucus production. Inflamm Bowel Dis. 2015;21(5):1006–1017.
  • Wallace JL, Motta J-P, Buret AG. Hydrogen sulfide: an agent of stability at the microbiome-mucosa interface. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2018;314(2):G143–g149.
  • Gemici B, Elsheikh W, Feitosa KB, et al. H2S-releasing drugs: anti-inflammatory, cytoprotective and chemopreventative potential. Nitric Oxide. 2015;46:25–31.
  • Kashfi K, Olson KR. Biology and therapeutic potential of hydrogen sulfide and hydrogen sulfide-releasing chimeras. Biochem Pharmacol. 2013;85(5):689–703.
  • Faris P, Ferulli F, Vismara M, et al. Hydrogen Sulfide-Evoked Intracellular Ca2+ Signals in Primary Cultures of Metastatic Colorectal Cancer Cells. Cancers (Basel). 2020;12(11):3338.
  • Kodela R, Nath N, Chattopadhyay M, et al. Hydrogen sulfide-releasing naproxen suppresses colon cancer cell growth and inhibits NF-κB signaling.. Drug Des Devel Ther. 2015;9:4873–4882.
  • Rhee K-J, Wu S, Wu X, et al. Induction of persistent colitis by a human commensal, enterotoxigenic Bacteroides fragilis, in wild-type C57BL/6 mice. Infect Immun. 2009;77(4):1708–1718.
  • Wu S, Rhee K-J, Zhang M, et al. Bacteroides fragilis toxin stimulates intestinal epithelial cell shedding and -secretase-dependent E-cadherin cleavage. J Cell Sci. 2007;120(11):1944–1952.
  • Wu S, Morin PJ, Maouyo D, et al. Bacteroides fragilis enterotoxin induces c-Myc expression and cellular proliferation. Gastroenterology. 2003;124(2):392–400.
  • Sears CL. Enterotoxigenic Bacteroides fragilis: a rogue among symbiotes. Table of Contents Clin Microbiol Rev. 2009;222:349–369.
  • Goodwin AC, Shields CED, Wu S, et al. Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis. Proc Natl Acad Sci U S A. 2011;108(37):15354–15359.
  • Snezhkina AV, Krasnov GS, Lipatova AV, et al. The Dysregulation of Polyamine Metabolism in Colorectal Cancer Is Associated with Overexpression of c-Myc and C/EBP β rather than Enterotoxigenic Bacteroides fragilis Infection. Oxid Med Cell Longev. 2016;2016:2353560.
  • Durant L, Watford WT, Ramos HL, et al. Diverse targets of the transcription factor STAT3 contribute to T cell pathogenicity and homeostasis. Immunity. 2010;32(5):605–615.
  • Wick EC, Rabizadeh S, Albesiano E, et al. Stat3 activation in murine colitis induced by enterotoxigenic Bacteroides fragilis. Inflamm Bowel Dis. 2014;20(5):821–834.
  • Guéry L, Hugues S. Th17 cell plasticity and functions in cancer immunity. Biomed Res Int. 2015;2015:314620.
  • Wu D, Wu P, Huang Q, et al. Interleukin-17: a promoter in colorectal cancer progression. Clin Dev Immunol. 2013;2013:436307.
  • Geis AL, Fan H, Wu X, et al. Regulatory T-cell Response to Enterotoxigenic Bacteroides fragilis Colonization Triggers IL17-Dependent Colon Carcinogenesis. Cancer Discov. 2015;5(10):1098–1109.
  • De Simone V, Franzè E, Ronchetti G, et al. Th17-type cytokines, IL-6 and TNF-α synergistically activate STAT3 and NF-kB to promote colorectal cancer cell growth. Oncogene. 2015;34(27):3493–3503.
  • Wu S, Rhee K-J, Albesiano E, et al. A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med. 2009;15(9):1016–1022.
  • 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;14(2):195–206.
  • Han YW, Ikegami A, Rajanna C, et al. Identification and characterization of a novel adhesin unique to oral fusobacteria. J Bacteriol. 2005;187(15):5330–5340.
  • Xu M, Yamada M, Li M, et al. FadA from Fusobacterium nucleatum utilizes both secreted and nonsecreted forms for functional oligomerization for attachment and invasion of host cells. J Biol Chem. 2007;282(34):25000–25009.
  • Fardini Y, Wang X, Témoin S, et al. Fusobacterium nucleatum adhesin FadA binds vascular endothelial cadherin and alters endothelial integrity. Mol Microbiol. 2011;82(6):1468–1480.
  • Sun C-H, Li -B-B, Wang B, et al. The role of Fusobacterium nucleatum in colorectal cancer: from carcinogenesis to clinical management. Chronic Dis Transl Med. 2019;5(3):178–187.
  • Cuevas-Ramos G, Petit CR, Marcq I, et al. Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. Proc Natl Acad Sci U S A. 2010;107(25):11537–11542.
  • Ge Z, Schauer DB, Fox JG. In vivo virulence properties of bacterial cytolethal-distending toxin. Cell Microbiol. 2008;10(8):1599–1607.
  • Taieb F, Petit C, Nougayrède J-P, et al. The enterobacterial genotoxins: cytolethal distending toxin and colibactin. EcoSal Plus. 2016;7(1). DOI:10.1128/ecosalplus.ESP-0008-2016
  • Buc E, Dubois D, Sauvanet P, et al. High prevalence of mucosa-associated E. coli producing cyclomodulin and genotoxin in colon cancer. PloS One. 2013;8(2):e56964.
  • Arthur JC, Perez-Chanona E, Mühlbauer M, et al. Intestinal inflammation targets cancer-inducing activity of the microbiota. Science. 2012;338(6103):120–123.
  • Nougayrède J-P, et al. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science. 2006;313(5788):848–851.
  • Arthur JC, Gharaibeh RZ, Mühlbauer M, et al. Microbial genomic analysis reveals the essential role of inflammation in bacteria-induced colorectal cancer. Nat Commun. 2014;5(1):4724.
  • Dalmasso G, Cougnoux A, Delmas J, et al. The bacterial genotoxin colibactin promotes colon tumor growth by modifying the tumor microenvironment. Gut Microbes. 2014;5(5):675–680.
  • Guerra L, Cortes-Bratti X, Guidi R, et al. The biology of the cytolethal distending toxins. Toxins (Basel). 2011;3(3):172–190.
  • He Z, Gharaibeh RZ, Newsome RC, et al. Campylobacter jejuni promotes colorectal tumorigenesis through the action of cytolethal distending toxin. Gut. 2019;68(2):289–300.
  • Li G, Niu H, Zhang Y, et al. Haemophilus parasuis cytolethal distending toxin induces cell cycle arrest and p53-dependent apoptosis. PloS One. 2017;12(5):e0177199.
  • Bezine E, Vignard J, Mirey G. The cytolethal distending toxin effects on Mammalian cells: a DNA damage perspective. Cells. 2014;3(2):592–615.
  • Asakura M, Hinenoya A, Alam MS, et al. An inducible lambdoid prophage encoding cytolethal distending toxin (Cdt-I) and a type III effector protein in enteropathogenic Escherichia coli. Proc Natl Acad Sci U S A. 2007;104(36):14483–14488.
  • Ge Z, Rogers AB, Feng Y, et al. Bacterial cytolethal distending toxin promotes the development of dysplasia in a model of microbially induced hepatocarcinogenesis. Cell Microbiol. 2007;9(8):2070–2080.
  • Gagnière J, et al. Gut microbiota imbalance and colorectal cancer. World J Gastroenterol. 2016;22(2):501–518.
  • Gao R, Gao Z, Huang L, et al. Gut microbiota and colorectal cancer. Eur J Clin Microbiol Infect Dis. 2017;36(5):757–769.
  • Lucas C, Barnich N, Nguyen HTT. Microbiota, Inflammation and Colorectal Cancer.. Int J Mol Sci. 2017;18(6). DOI:10.3390/ijms18061310
  • Bultman SJ. The microbiome and its potential as a cancer preventive intervention. Semin Oncol. 2016;43(1):97–106.
  • Mima K, Ogino S, Nakagawa S, et al. The role of intestinal bacteria in the development and progression of gastrointestinal tract neoplasms. Surg Oncol. 2017;26(4):368–376.
  • Sivan A, Corrales L, Hubert N, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015;350(6264):1084–1089.
  • Yuan L, et al. The influence of gut microbiota dysbiosis to the efficacy of 5-Fluorouracil treatment on colorectal cancer. Biomed Pharmacothe. 2018;108(184–193). DOI:10.1016/j.biopha.2018.08.165