Gut microbiota-derived metabolites in CRC progression and causation
Tóm tắt
Based on recent research reports, dysbiosis and improper concentrations of microbial metabolites in the gut may result into the carcinogenesis of colorectal cancer. Recent advancement also highlights the involvement of bacteria and their secreted metabolites in the cancer causation. Gut microbial metabolites are functional output of the host–microbiota interactions and produced by anaerobic fermentation of food components in the diet. They contribute to influence variety of biological mechanisms including inflammation, cell signaling, cell-cycle disruption which are majorly disrupted in carcinogenic activities. In this review, we intend to discuss recent updates and possible molecular mechanisms to provide the role of bacterial metabolites, gut bacteria and diet in the colorectal carcinogenesis. Recent evidences have proposed the role of bacteria, such as Fusobacterium nucleaturm, Streptococcus bovis, Helicobacter pylori, Bacteroides fragilis and Clostridium septicum, in the carcinogenesis of CRC. Metagenomic study confirmed that these bacteria are in increased abundance in CRC patient as compared to healthy individuals and can cause inflammation and DNA damage which can lead to development of cancer. These bacteria produce metabolites, such as secondary bile salts from primary bile salts, hydrogen sulfide, trimethylamine-N-oxide (TMAO), which are likely to promote inflammation and subsequently cancer development. Recent studies suggest that gut microbiota-derived metabolites have a role in CRC progression and causation and hence, could be implicated in CRC diagnosis, prognosis and therapy.
Tài liệu tham khảo
Abdulamir AS, Hafidh RR, Bakar FA (2010) Molecular detection, quantification, and isolation of Streptococcus gallolyticus bacteria colonizing colorectal tumors: inflammation-driven potential of carcinogenesis via IL-1, COX-2, and IL-8. Mol Cancer 9:249. https://doi.org/10.1186/1476-4598-9-249
Abdulamir AS, Hafidh RR, Abu Bakar F (2011) The association of Streptococcus bovis/gallolyticus with colorectal tumors: the nature and the underlying mechanisms of its etiological role. J Exp Clin Cancer Res 30:11. https://doi.org/10.1186/1756-9966-30-11
Ahn J, Sinha R, Pei Z et al (2013) Human gut microbiome and risk for colorectal cancer. J Natl Cancer Inst 105:1907–1911. https://doi.org/10.1093/jnci/djt300
Ai D, Pan H, Li X et al (2019) Identifying gut microbiota associated with colorectal cancer using a zero-inflated lognormal model. Front Microbiol. https://doi.org/10.3389/fmicb.2019.00826
Al Hinai EA, Kullamethee P, Rowland IR et al (2018) Modelling the role of microbial p-cresol in colorectal genotoxicity. Gut Microbes 10:398–411. https://doi.org/10.1080/19490976.2018.1534514
Alhinai EA, Walton GE, Commane DM (2019) The role of the gut microbiota in colorectal cancer causation. IJMS 20:5295. https://doi.org/10.3390/ijms20215295
Amarnani R, Rapose A (2017) Colon cancer and enterococcus bacteremia co-affection: a dangerous alliance. J Infect Public Health 10:681–684. https://doi.org/10.1016/j.jiph.2016.09.009
Andriamihaja M, Lan A, Beaumont M et al (2015) The deleterious metabolic and genotoxic effects of the bacterial metabolite p-cresol on colonic epithelial cells. Free Radic Biol Med 85:219–227. https://doi.org/10.1016/j.freeradbiomed.2015.04.004
Armaghany T, Wilson JD, Chu Q, Mills G (2012) Genetic alterations in colorectal cancer. Gastrointest Cancer Res 5:19–27
Bae S, Ulrich CM, Neuhouser ML et al (2014) Plasma choline metabolites and colorectal cancer risk in the Women’s health initiative observational study. Cancer Res 74:7442–7452. https://doi.org/10.1158/0008-5472.CAN-14-1835
Balamurugan R, Rajendiran E, George S et al (2008) Real-time polymerase chain reaction quantification of specific butyrate-producing bacteria, Desulfovibrio and Enterococcus faecalis in the feces of patients with colorectal cancer. J Gastroenterol Hepatol 23:1298–1303. https://doi.org/10.1111/j.1440-1746.2008.05490.x
Beaumont M, Neyrinck AM, Olivares M et al (2018) The gut microbiota metabolite indole alleviates liver inflammation in mice. FASEB J. https://doi.org/10.1096/fj.201800544
Biarc J, Nguyen IS, Pini A et al (2004) Carcinogenic properties of proteins with pro-inflammatory activity from Streptococcus infantarius (formerly S. bovis). Carcinogenesis 25:1477–1484. https://doi.org/10.1093/carcin/bgh091
Boleij A, van Gelder MMHJ, Swinkels DW, Tjalsma H (2011) Clinical importance of Streptococcus gallolyticus infection among colorectal cancer patients: systematic review and meta-analysis. Clin Infect Dis 53:870–878. https://doi.org/10.1093/cid/cir609
Boleij A, Hechenbleikner EM, Goodwin AC et al (2015) The Bacteroides fragilis toxin gene is prevalent in the colon mucosa of colorectal cancer patients. Clin Infect Dis 60:208–215. https://doi.org/10.1093/cid/ciu787
Buc E, Dubois D, Sauvanet P et al (2013) High prevalence of mucosa-associated E. coli producing cyclomodulin and genotoxin in colon cancer. PLoS ONE 8:e56964. https://doi.org/10.1371/journal.pone.0056964
Capaldo CT, Powell DN, Kalman D (2017) Layered defense: how mucus and tight junctions seal the intestinal barrier. J Mol Med 95:927–934. https://doi.org/10.1007/s00109-017-1557-x
Cassidy A, Minihane A-M (2017) The role of metabolism (and the microbiome) in defining the clinical efficacy of dietary flavonoids. Am J Clin Nutr 105:10–22. https://doi.org/10.3945/ajcn.116.136051
Chakravorty A, Awad MM, Cheung JK et al (2015) The pore-forming α-toxin from Clostridium septicum activates the MAPK pathway in a Ras-c-Raf-dependent and independent manner. Toxins (basel) 7:516–534. https://doi.org/10.3390/toxins7020516
Chan CWH, Law BMH, Waye MMY et al (2019) 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 10:5874–5882. https://doi.org/10.7150/jca.31737
Chang H, Lei L, Zhou Y et al (2018) Dietary flavonoids and the risk of colorectal cancer: an updated meta-analysis of epidemiological studies. Nutrients. https://doi.org/10.3390/nu10070950
Chen W, Liu F, Ling Z et al (2012) Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer. PLoS ONE 7:e39743. https://doi.org/10.1371/journal.pone.0039743
Chen H-M, Yu Y-N, Wang J-L et al (2013) Decreased dietary fiber intake and structural alteration of gut microbiota in patients with advanced colorectal adenoma. Am J Clin Nutr 97:1044–1052. https://doi.org/10.3945/ajcn.112.046607
Chen J, Pitmon E, Wang K (2017) Microbiome, inflammation and colorectal cancer. Semin Immunol 32:43–53. https://doi.org/10.1016/j.smim.2017.09.006
Chen M, Zhu X, Ran L et al (2017) Trimethylamine-N-oxide induces vascular inflammation by activating the NLRP3 inflammasome through the SIRT3-SOD2-mtROS signaling pathway. J Am Heart Assoc 6:e006347. https://doi.org/10.1161/JAHA.117.006347
Chew SS, Lubowski DZ (2001a) Clostridium septicum and malignancy. ANZ J Surg 71:647–649. https://doi.org/10.1046/j.1445-1433.2001.02231.x
Cipe G, Idiz UO, Firat D, Bektasoglu H (2015) Relationship between intestinal microbiota and colorectal cancer. World J Gastrointest Oncol 7:233–240. https://doi.org/10.4251/wjgo.v7.i10.233
Cohen LJ, Kang H-S, Chu J et al (2015) Functional metagenomic discovery of bacterial effectors in the human microbiome and isolation of commendamide, a GPCR G2A/132 agonist. Proc Natl Acad Sci USA 112:E4825-4834. https://doi.org/10.1073/pnas.1508737112
Cook JW, Kennaway EL, Kennaway NM (1940) Production of tumours in mice by deoxycholic acid. Nature 145:627–627. https://doi.org/10.1038/145627a0
Corredoira J, Grau I, Garcia-Rodriguez JF et al (2017) Colorectal neoplasm in cases of Clostridium septicum and Streptococcus gallolyticus subsp. gallolyticus bacteraemia. Eur J Intern Med 41:68–73. https://doi.org/10.1016/j.ejim.2017.02.009
Cross AJ, Moore SC, Boca S et al (2014) A prospective study of serum metabolites and colorectal cancer risk. Cancer 120:3049–3057. https://doi.org/10.1002/cncr.28799
Dahmus JD, Kotler DL, Kastenberg DM, Kistler CA (2018) The gut microbiome and colorectal cancer: a review of bacterial pathogenesis. J Gastrointest Oncol 9:769–777. https://doi.org/10.21037/jgo.2018.04.07
Dai Z, Zhang J, Wu Q et al (2019) The role of microbiota in the development of colorectal cancer. Int J Cancer 145:2032–2041. https://doi.org/10.1002/ijc.32017
Dalal N, Jalandra R, Sharma M et al (2020) Omics technologies for improved diagnosis and treatment of colorectal cancer: technical advancement and major perspectives. Biomed Pharmacother 131:110648. https://doi.org/10.1016/j.biopha.2020.110648
den Besten G, van Eunen K, Groen AK et al (2013) The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res 54:2325–2340. https://doi.org/10.1194/jlr.R036012
Devlin AS, Marcobal A, Dodd D et al (2016) Modulation of a circulating uremic solute via rational genetic manipulation of the gut microbiota. Cell Host Microbe 20:709–715. https://doi.org/10.1016/j.chom.2016.10.021
Dieterich W, Schink M, Zopf Y (2018) Microbiota in the gastrointestinal tract. Med Sci (basel). https://doi.org/10.3390/medsci6040116
Diether NE, Willing BP (2019) Microbial fermentation of dietary protein: an important factor in diet–microbe–host interaction. Microorganisms. https://doi.org/10.3390/microorganisms7010019
Donohoe DR, Garge N, Zhang X et al (2011) The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metab 13:517–526. https://doi.org/10.1016/j.cmet.2011.02.018
Dziubańska-Kusibab PJ, Berger H, Battistini F et al (2020) Colibactin DNA-damage signature indicates mutational impact in colorectal cancer. Nat Med 26:1063–1069. https://doi.org/10.1038/s41591-020-0908-2
Elliott TR, Hudspith BN, Wu G et al (2013) Quantification and characterization of mucosa-associated and intracellular Escherichia coli in inflammatory bowel disease. Inflamm Bowel Dis 19:2326–2338. https://doi.org/10.1097/MIB.0b013e3182a38a92
Fan P, Li L, Rezaei A et al (2015) Metabolites of dietary protein and peptides by intestinal microbes and their impacts on gut. Curr Protein Pept Sci 16:646–654. https://doi.org/10.2174/1389203716666150630133657
Fang H, Kang J, Zhang D (2017) Microbial production of vitamin B12: a review and future perspectives. Microb Cell Fact. https://doi.org/10.1186/s12934-017-0631-y
Feng Q, Chen W-D, Wang Y-D (2018) Gut microbiota: an integral moderator in health and disease. Front Microbiol 9:151. https://doi.org/10.3389/fmicb.2018.00151
Fischbach MA, Sonnenburg JL (2011) Eating for two: how metabolism establishes interspecies interactions in the gut. Cell Host Microbe 10:336–347. https://doi.org/10.1016/j.chom.2011.10.002
Forgie AJ, Fouhse JM, Willing BP (2019) Diet–microbe–host interactions that affect gut mucosal integrity and infection resistance. Front Immunol. https://doi.org/10.3389/fimmu.2019.01802
Gao Z, Guo B, Gao R et al (2015) Microbiota disbiosis is associated with colorectal cancer. Front Microbiol 6:20. https://doi.org/10.3389/fmicb.2015.00020
Gausachs M, Borras E, Chang K et al (2017) Mutational heterogeneity in APC and KRAS arises at the crypt level and leads to polyclonality in early colorectal tumorigenesis. Clin Cancer Res 23:5936–5947. https://doi.org/10.1158/1078-0432.CCR-17-0821
Georgescauld F, Mocan I, Lacombe M-L, Lascu I (2009) Rescue of the neuroblastoma mutant of the human nucleoside diphosphate kinase A/nm23-H1 by the natural osmolyte trimethylamine-N-oxide. FEBS Lett 583:820–824. https://doi.org/10.1016/j.febslet.2009.01.043
Gil-Cardoso K, Ginés I, Pinent M et al (2016) Effects of flavonoids on intestinal inflammation, barrier integrity and changes in gut microbiota during diet-induced obesity. Nutr Res Rev 29:234–248. https://doi.org/10.1017/S0954422416000159
Giovannucci E (2004) Alcohol, one-carbon metabolism, and colorectal cancer: recent insights from molecular studies. J Nutr 134:2475S-2481S. https://doi.org/10.1093/jn/134.9.2475S
Goodwin AC, Destefano Shields CE, Wu S et al (2011) Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced colon tumorigenesis. Proc Natl Acad Sci USA 108:15354–15359. https://doi.org/10.1073/pnas.1010203108
Guertin KA, Li XS, Graubard BI et al (2017) Serum Trimethylamine N-oxide, carnitine, choline, and betaine in relation to colorectal cancer risk in the alpha tocopherol, beta carotene cancer prevention study. Cancer Epidemiol Biomark Prev 26:945–952. https://doi.org/10.1158/1055-9965.EPI-16-0948
Gur C, Ibrahim Y, Isaacson B et al (2015) Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity 42:344–355. https://doi.org/10.1016/j.immuni.2015.01.010
Hartwich A, Konturek S, Pierzchalski P et al (2001) Helicobacter pylori infection, gastrin, cyclooxygenase-2, and apoptosis in colorectal cancer. Int J Colorectal Dis 16:202–210. https://doi.org/10.1007/s003840100288
Howarth NC, Murphy SP, Wilkens LR et al (2008) The association of glycemic load and carbohydrate intake with colorectal cancer risk in the Multiethnic Cohort Study. Am J Clin Nutr 88:1074–1082
Huycke MM, Abrams V, Moore DR (2002) Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis 23:529–536. https://doi.org/10.1093/carcin/23.3.529
Jahani-Sherafat S, Alebouyeh M, Moghim S et al (2018) Role of gut microbiota in the pathogenesis of colorectal cancer; a review article. Gastroenterol Hepatol Bed Bench 11:101–109
Jakobsson HE, Rodríguez-Piñeiro AM, Schütte A et al (2015) The composition of the gut microbiota shapes the colon mucus barrier. EMBO Rep 16:164–177. https://doi.org/10.15252/embr.201439263
Johnson CH, Dejea CM, Edler D et al (2015) Metabolism links bacterial biofilms and colon carcinogenesis. Cell Metab 21:891–897. https://doi.org/10.1016/j.cmet.2015.04.011
Kantor ED, Lampe JW, Peters U et al (2014) Long-chain omega-3 polyunsaturated fatty acid intake and risk of colorectal cancer. Nutr Cancer 66:716–727. https://doi.org/10.1080/01635581.2013.804101
Kasai C, Sugimoto K, Moritani I et al (2016) Comparison of human gut microbiota in control subjects and patients with colorectal carcinoma in adenoma: terminal restriction fragment length polymorphism and next-generation sequencing analyses. Oncol Rep 35:325–333. https://doi.org/10.3892/or.2015.4398
Kasper SH, Morell-Perez C, Wyche TP et al (2020) Colorectal cancer-associated anaerobic bacteria proliferate in tumor spheroids and alter the microenvironment. Sci Rep. https://doi.org/10.1038/s41598-020-62139-z
Kato I, Boleij A, Kortman GAM et al (2013) Partial associations of dietary iron, smoking and intestinal bacteria with colorectal cancer risk. Nutr Cancer 65:169–177. https://doi.org/10.1080/01635581.2013.748922
Kennedy CL, Krejany EO, Young LF et al (2005) The alpha-toxin of Clostridium septicum is essential for virulence. Mol Microbiol 57:1357–1366. https://doi.org/10.1111/j.1365-2958.2005.04774.x
Kim TJ (2017) Helicobacter pylori infection is an independent risk factor of early and advanced colorectal neoplasm—Helicobacter—Wiley Online Library. https://doi.org/10.1111/hel.12377. Accessed 18 Dec 2020
Kim K-B, Yang J-Y, Kwack SJ et al (2010) Toxicometabolomics of urinary biomarkers for human gastric cancer in a mouse model. J Toxicol Environ Health A 73:1420–1430. https://doi.org/10.1080/15287394.2010.511545
Kim E-K, Cho JH, Kim E, Kim YJ (2017) Ursodeoxycholic acid inhibits the proliferation of colon cancer cells by regulating oxidative stress and cancer stem-like cell growth. PLoS ONE 12:e0181183. https://doi.org/10.1371/journal.pone.0181183
Kim YH, Kim JH, Kim BG et al (2019) Tauroursodeoxycholic acid attenuates colitis-associated colon cancer by inhibiting nuclear factor kappaB signaling. J Gastroenterol Hepatol 34:544–551. https://doi.org/10.1111/jgh.14526
King M, Hurley H, Davidson KR et al (2020) The link between fusobacteria and colon cancer: a fulminant example and review of the evidence. Immune Netw 20:e30. https://doi.org/10.4110/in.2020.20.e30
Kishino S, Takeuchi M, Park S-B et al (2013) Polyunsaturated fatty acid saturation by gut lactic acid bacteria affecting host lipid composition. Proc Natl Acad Sci USA 110:17808–17813. https://doi.org/10.1073/pnas.1312937110
Klampfer L, Huang J, Sasazuki T et al (2003) Inhibition of interferon gamma signaling by the short chain fatty acid butyrate. Mol Cancer Res 1:855–862
Knip M, Siljander H (2016) The role of the intestinal microbiota in type 1 diabetes mellitus. Nat Rev Endocrinol 12:154–167. https://doi.org/10.1038/nrendo.2015.218
Koeth RA, Wang Z, Levison BS et al (2013) Intestinal microbiota metabolism of l-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 19:576–585. https://doi.org/10.1038/nm.3145
Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F (2016) From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. Cell 165:1332–1345. https://doi.org/10.1016/j.cell.2016.05.041
Kostic AD, Gevers D, Pedamallu CS et al (2012) Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. In: Genome research. https://pubmed.ncbi.nlm.nih.gov/22009990/. Accessed 18 Sep 2020
Kostic AD, Chun E, Robertson L et al (2013) Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14:207–215. https://doi.org/10.1016/j.chom.2013.07.007
Lee DW, Han SW, Kang JK, et al (2018) Association between Fusobacterium nucleatum, Pathway Mutation, and Patient Prognosis in colorectal cancer. In: Annals of surgical oncology. https://pubmed.ncbi.nlm.nih.gov/30062471/. Accessed 18 Sept 2020
Levy M, Thaiss CA, Zeevi D et al (2015) Microbiota-modulated metabolites shape the intestinal microenvironment by regulating NLRP6 inflammasome signaling. Cell 163:1428–1443. https://doi.org/10.1016/j.cell.2015.10.048
Lichtenstern CR, Ngu RK, Shalapour S, Karin M (2020) Immunotherapy, inflammation and colorectal cancer. Cells. https://doi.org/10.3390/cells9030618
Liu X, Liu H, Yuan C et al (2017) Preoperative serum TMAO level is a new prognostic marker for colorectal cancer. Biomark Med 11:443–447. https://doi.org/10.2217/bmm-2016-0262
Liu T, Song X, Khan S et al (2020) The gut microbiota at the intersection of bile acids and intestinal carcinogenesis: an old story, yet mesmerizing. Int J Cancer 146:1780–1790. https://doi.org/10.1002/ijc.32563
Long X, Wong CC, Tong L et al (2019) Peptostreptococcus anaerobius promotes colorectal carcinogenesis and modulates tumour immunity. Nat Microbiol 4:2319–2330. https://doi.org/10.1038/s41564-019-0541-3
Lu R, Wu S, Zhang Y et al (2014) Enteric bacterial protein AvrA promotes colonic tumorigenesis and activates colonic beta-catenin signaling pathway. Oncogenesis 3:e105. https://doi.org/10.1038/oncsis.2014.20
Lu R, Wu S, Zhang Y-G et al (2016) Salmonella protein AvrA activates the STAT3 signaling pathway in colon cancer. Neoplasia 18:307–316. https://doi.org/10.1016/j.neo.2016.04.001
Lucas C, Barnich N, Nguyen HTT (2017) Microbiota, inflammation and colorectal cancer. Int J Mol Sci. https://doi.org/10.3390/ijms18061310
Lührs H, Gerke T, Müller JG et al (2002) Butyrate inhibits NF-kappaB activation in lamina propria macrophages of patients with ulcerative colitis. Scand J Gastroenterol 37:458–466. https://doi.org/10.1080/003655202317316105
Lunn JC, Kuhnle G, Mai V et al (2007) The effect of haem in red and processed meat on the endogenous formation of N-nitroso compounds in the upper gastrointestinal tract. Carcinogenesis 28:685–690. https://doi.org/10.1093/carcin/bgl192
Mager LF, Burkhard R, Pett N et al (2020) Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy. Science 369:1481–1489. https://doi.org/10.1126/science.abc3421
Maino Vieytes CA, Taha HM, Burton-Obanla AA et al (2019) Carbohydrate nutrition and the risk of cancer. Curr Nutr Rep 8:230–239. https://doi.org/10.1007/s13668-019-0264-3
Martin HM, Campbell BJ, Hart CA et al (2004) Enhanced Escherichia coli adherence and invasion in Crohn’s disease and colon cancer. Gastroenterology 127:80–93. https://doi.org/10.1053/j.gastro.2004.03.054
Maslowski KM, Vieira AT, Ng A et al (2009) Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461:1282–1286. https://doi.org/10.1038/nature08530
McCoy AN, Araújo-Pérez F, Azcárate-Peril A et al (2013) Fusobacterium is associated with colorectal adenomas. PLoS ONE 8:e53653. https://doi.org/10.1371/journal.pone.0053653
McNabney SM, Henagan TM (2017) Short chain fatty acids in the colon and peripheral tissues: a focus on butyrate, colon cancer. Obes Insulin Resist Nutr. https://doi.org/10.3390/nu9121348
Meijnikman AS, Gerdes VE, Nieuwdorp M, Herrema H (2018) Evaluating causality of gut microbiota in obesity and diabetes in humans. Endocr Rev 39:133–153. https://doi.org/10.1210/er.2017-00192
Nam JH, Hong CW, Kim BC et al (2017) Helicobacter pylori infection is an independent risk factor for colonic adenomatous neoplasms. Cancer Causes Control 28:107–115. https://doi.org/10.1007/s10552-016-0839-x
Neoptolemos JP, Clayton H, Heagerty AM et al (1988) Dietary fat in relation to fatty acid composition of red cells and adipose tissue in colorectal cancer. Br J Cancer 58:575–579. https://doi.org/10.1038/bjc.1988.262
Nougayrède J-P, Homburg S, Taieb F et al (2006) Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science 313:848–851. https://doi.org/10.1126/science.1127059
O’Keefe SJD (2016) Diet, microorganisms and their metabolites, and colon cancer. Nat Rev Gastroenterol Hepatol 13:691–706. https://doi.org/10.1038/nrgastro.2016.165
O’Keefe SJD, Li JV, Lahti L et al (2015) Fat, fibre and cancer risk in African Americans and rural Africans. Nat Commun 6:6342. https://doi.org/10.1038/ncomms7342
Ocvirk S, O’Keefe SJ (2017) Influence of bile acids on colorectal cancer risk: potential mechanisms mediated by diet–gut microbiota interactions. Curr Nutr Rep 6:315–322. https://doi.org/10.1007/s13668-017-0219-5
Ocvirk S, Wilson AS, Posma JM et al (2020) A prospective cohort analysis of gut microbial co-metabolism in Alaska Native and rural African people at high and low risk of colorectal cancer. Am J Clin Nutr 111:406–419. https://doi.org/10.1093/ajcn/nqz301
Ohira H, Tsutsui W, Fujioka Y (2017) Are short chain fatty acids in gut microbiota defensive players for inflammation and atherosclerosis? J Atheroscler Thromb 24:660–672. https://doi.org/10.5551/jat.RV17006
Oliphant K, Allen-Vercoe E (2019) Macronutrient metabolism by the human gut microbiome: major fermentation by-products and their impact on host health. Microbiome. https://doi.org/10.1186/s40168-019-0704-8
Parada Venegas D, De la Fuente MK, Landskron G et al (2019) Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Front Immunol. https://doi.org/10.3389/fimmu.2019.00277
Payne CM, Weber C, Crowley-Skillicorn C et al (2007) Deoxycholate induces mitochondrial oxidative stress and activates NF-kappaB through multiple mechanisms in HCT-116 colon epithelial cells. Carcinogenesis 28:215–222. https://doi.org/10.1093/carcin/bgl139
Powolny A, Xu J, Loo G (2001) Deoxycholate induces DNA damage and apoptosis in human colon epithelial cells expressing either mutant or wild-type p53. Int J Biochem Cell Biol 33:193–203. https://doi.org/10.1016/s1357-2725(00)00080-7
Prasad KN, Bondy SC (2019) Dietary fibers and their fermented short-chain fatty acids in prevention of human diseases. Bioact Carbohydr Diet Fibre 17:100170. https://doi.org/10.1016/j.bcdf.2018.09.001
Research AA for C (2020) Colibactin causes colorectal cancer-associated mutational signature. Cancer Discov 10:635–635. https://doi.org/10.1158/2159-8290.CD-RW2020-037
Rooks MG, Garrett WS (2016) Gut microbiota, metabolites and host immunity. Nat Rev Immunol 16:341–352. https://doi.org/10.1038/nri.2016.42
Rothhammer V, Mascanfroni ID, Bunse L et al (2016) Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med 22:586–597. https://doi.org/10.1038/nm.4106
Rothhammer V, Borucki DM, Tjon EC et al (2018) Microglial control of astrocytes in response to microbial metabolites. Nature 557:724–728. https://doi.org/10.1038/s41586-018-0119-x
Rowland I, Gibson G, Heinken A et al (2018) Gut microbiota functions: metabolism of nutrients and other food components. Eur J Nutr 57:1–24. https://doi.org/10.1007/s00394-017-1445-8
Rubinstein MR, Wang X, Liu W et al (2013) Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell Host Microbe 14:195–206. https://doi.org/10.1016/j.chom.2013.07.012
Rubinstein MR, Baik JE, Lagana SM et al (2019) Fusobacterium nucleatum promotes colorectal cancer by inducing Wnt/β-catenin modulator Annexin A1. EMBO Rep. https://doi.org/10.15252/embr.201847638
Schulthess J, Pandey S, Capitani M et al (2019) The short chain fatty acid butyrate imprints an antimicrobial program in macrophages. Immunity 50:432-445.e7. https://doi.org/10.1016/j.immuni.2018.12.018
Sears CL (2001) The toxins of Bacteroides fragilis. Toxicon 39:1737–1746. https://doi.org/10.1016/s0041-0101(01)00160-x
Seesaha PK, Chen X, Wu X et al (2020) The interplay between dietary factors, gut microbiome and colorectal cancer: a new era of colorectal cancer prevention. Future Oncol 16:293–306. https://doi.org/10.2217/fon-2019-0552
Shmuely H, Passaro D, Figer A et al (2001) Relationship between Helicobacter pylori CagA status and colorectal cancer. Am J Gastroenterol 96:3406–3410. https://doi.org/10.1111/j.1572-0241.2001.05342.x
Sivaprakasam S, Prasad PD, Singh N (2016) Benefits of short-chain fatty acids and their receptors in inflammation and carcinogenesis. Pharmacol Ther 164:144–151. https://doi.org/10.1016/j.pharmthera.2016.04.007
Slattery ML, Potter JD, Duncan DM, Berry TD (1997) Dietary fats and colon cancer: assessment of risk associated with specific fatty acids. Int J Cancer 73:670–677. https://doi.org/10.1002/(sici)1097-0215(19971127)73:5%3c670::aid-ijc10%3e3.0.co;2-a
Solé C, Guilly S, Da Silva K et al (2021) Alterations in gut microbiome in cirrhosis as assessed by quantitative metagenomics: relationship with acute-on-chronic liver failure and prognosis. Gastroenterology 160:206-218.e13. https://doi.org/10.1053/j.gastro.2020.08.054
Sun J, Kato I (2016) Gut microbiota, inflammation and colorectal cancer. Genes Dis 3:130–143. https://doi.org/10.1016/j.gendis.2016.03.004
Tatishchev SF, VanBeek C, Wang HL (2012) Helicobacter pylori infection and colorectal carcinoma: is there a causal association? J Gastrointest Oncol 3:380–385. https://doi.org/10.3978/j.issn.2078-6891.2012.058
Theodoratou E, Kyle J, Cetnarskyj R et al (2007) Dietary flavonoids and the risk of colorectal cancer. Cancer Epidemiol Biomark Prev 16:684–693. https://doi.org/10.1158/1055-9965.EPI-06-0785
Thomas AM, Manghi P, Asnicar F et al (2019) Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation. Nat Med 25:667–678. https://doi.org/10.1038/s41591-019-0405-7
Tsoi H, Chu ESH, Zhang X et al (2017) Peptostreptococcus anaerobius induces intracellular cholesterol biosynthesis in colon cells to induce proliferation and causes dysplasia in mice. Gastroenterology 152:1419–1433. https://doi.org/10.1053/j.gastro.2017.01.009 (e5)
Tuttolomondo A, Di Raimondo D, Pecoraro R et al (2012) Atherosclerosis as an inflammatory disease. Curr Pharm Des 18:4266–4288. https://doi.org/10.2174/138161212802481237
Vernocchi P, Del Chierico F, Putignani L (2020) Gut microbiota metabolism and interaction with food components. Int J Mol Sci 21:3688. https://doi.org/10.3390/ijms21103688
Viljoen KS, Dakshinamurthy A, Goldberg P, Blackburn JM (2015) Quantitative profiling of colorectal cancer-associated bacteria reveals associations between Fusobacterium spp., enterotoxigenic Bacteroides fragilis (ETBF) and clinicopathological features of colorectal cancer. PLoS ONE 10:e0119462. https://doi.org/10.1371/journal.pone.0119462
Vipperla K, O’Keefe SJ (2016) Diet, microbiota, and dysbiosis: a ‘recipe’ for colorectal cancer. Food Funct 7:1731–1740. https://doi.org/10.1039/C5FO01276G
Wang Z, Zhao Y (2018) Gut microbiota derived metabolites in cardiovascular health and disease. Protein Cell 9:416–431. https://doi.org/10.1007/s13238-018-0549-0
Wang C, Ruan P, Zhao Y et al (2017) Spermidine/spermine N1-acetyltransferase regulates cell growth and metastasis via AKT/β-catenin signaling pathways in hepatocellular and colorectal carcinoma cells. Oncotarget 8:1092–1109. https://doi.org/10.18632/oncotarget.13582
Wang G, Yu Y, Wang Y-Z et al (2019) Role of SCFAs in gut microbiome and glycolysis for colorectal cancer therapy. J Cell Physiol 234:17023–17049. https://doi.org/10.1002/jcp.28436
Weng Z, Patel AB, Panagiotidou S, Theoharides TC (2015) The novel flavone tetramethoxyluteolin is a potent inhibitor of human mast cells. J Allergy Clin Immunol 135:1044–1052. https://doi.org/10.1016/j.jaci.2014.10.032 (e5)
Wessler S, Krisch LM, Elmer DP, Aberger F (2017) From inflammation to gastric cancer—the importance of Hedgehog/GLI signaling in Helicobacter pylori-induced chronic inflammatory and neoplastic diseases. Cell Commun Signal 15:15. https://doi.org/10.1186/s12964-017-0171-4
Wilson AJ, Chueh AC, Tögel L et al (2010) Apoptotic sensitivity of colon cancer cells to histone deacetylase inhibitors is mediated by an Sp1/Sp3-activated transcriptional program involving immediate-early gene induction. Cancer Res 70:609–620. https://doi.org/10.1158/0008-5472.CAN-09-2327
Wirbel J, Pyl PT, Kartal E et al (2019) Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat Med 25:679–689. https://doi.org/10.1038/s41591-019-0406-6
Yachida S, Mizutani S, Shiroma H et al (2019) Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nat Med 25:968–976. https://doi.org/10.1038/s41591-019-0458-7
Yan S, Huang J, Chen Z et al (2016) Metabolomics in gut microbiota: applications and challenges. Sci Bull 61:1151–1153. https://doi.org/10.1007/s11434-016-1142-7
Yang Y, Weng W, Peng J et al (2017) Fusobacterium nucleatum increases proliferation of colorectal cancer cells and tumor development in mice by activating toll-like receptor 4 signaling to nuclear factor-κB, and up-regulating expression of MicroRNA-21. In: Gastroenterology. https://pubmed.ncbi.nlm.nih.gov/27876571/. Accessed 18 Sept 2020
Yao L, Seaton SC, Ndousse-Fetter S et al (2018) A selective gut bacterial bile salt hydrolase alters host metabolism. Elife. https://doi.org/10.7554/eLife.37182
Ye X, Wang R, Bhattacharya R et al (2017) Fusobacterium nucleatum subspecies animalis influences proinflammatory cytokine expression and monocyte activation in human colorectal tumors. Cancer Prev Res (phila) 10:398–409. https://doi.org/10.1158/1940-6207.CAPR-16-0178
Zackular JP, Baxter NT, Iverson KD et al (2013) The gut microbiome modulates colon tumorigenesis. Mbio. https://doi.org/10.1128/mBio.00692-13
Zamani S, Taslimi R, Sarabi A et al (2019) Enterotoxigenic Bacteroides fragilis: a possible etiological candidate for bacterially-induced colorectal precancerous and cancerous lesions. Front Cell Infect Microbiol 9:449. https://doi.org/10.3389/fcimb.2019.00449
Zeng H, Umar S, Rust B et al (2019) Secondary bile acids and short chain fatty acids in the colon: a focus on colonic microbiome, cell proliferation, inflammation, and cancer. Int J Mol Sci. https://doi.org/10.3390/ijms20051214
Zhang H, Zhang A, Miao J et al (2019) Targeting regulation of tryptophan metabolism for colorectal cancer therapy: a systematic review. RSC Adv 9:3072–3080. https://doi.org/10.1039/C8RA08520J
Zhou Y, He H, Xu H et al (2016) Association of oncogenic bacteria with colorectal cancer in South China. Oncotarget 7:80794–80802. https://doi.org/10.18632/oncotarget.13094