Host's physiology is significantly influenced by microbiota colonizing the epithelial surfaces. Complex microbial communities contribute to proper mucosal barrier function, immune response, and prevention of pathogen invasion and have many other crucial functions. The oral cavity and large intestine are distant parts of the digestive tract, both heavily colonized by commensal microbiota. Nevertheless, they feature different proportions of major bacterial and fungal phyla, mostly due to distinct epithelial layers organization and different oxygen levels. A few obligate anaerobic strains inhabiting the oral cavity are involved in the pathogenesis of oral diseases. Interestingly, these microbiota components are also enriched in gut inflammatory and tumor tissue. An altered microbiota composition - dysbiosis - and formation of polymicrobial biofilms seem to play important roles in the development of oral diseases and colorectal cancer. In this review, we describe the differences in composition of commensal microbiota in the oral cavity and large intestine and the mechanisms by which microbiota affect the inflammatory and carcinogenic response of the host.

Laboratory of Cellular and Molecular Immunology Institute of Microbiology of the CAS Prague Czechia

Zobrazit více v PubMed

Aagaard K., Ma J., Antony K. M., Ganu R., Petrosino J., Versalovic J. (2014). The placenta harbors a unique microbiome. Sci. Transl. Med. 6:237ra65. 10.1126/scitranslmed.3008599 PubMed DOI PMC

Aas J. A., Paster B. J., Stokes L. N., Olsen I., Dewhirst F. E. (2005). Defining the normal bacterial flora of the oral cavity. J. Clin. Microbiol. 43 5721–5732. 10.1128/Jcm.43.11.5721-5732.2005 PubMed DOI PMC

Abed J., Emgard J. E. M., Zamir G., Faroja M., Almogy G., Grenov A., et al. (2016). Fap2 mediates Fusobacterium nucleatum colorectal adenocarcinoma enrichment by binding to tumor-expressed Gal-GalNAc. Cell Host Microbe 20 215–225. 10.1016/j.chom.2016.07.006 PubMed DOI PMC

Abreu M. T. (2010). Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function. Nat. Rev. Immunol. 10 131–144. 10.1038/nri2707 PubMed DOI

Adlerberth I., Wold A. E. (2009). Establishment of the gut microbiota in Western infants. Acta Paediatr. 98 229–238. 10.1111/j.1651-2227.2008.01060.x PubMed DOI

Amitay E. L., Werner S., Vital M., Pieper D. H., Hofler D., Gierse I. J., et al. (2017). Fusobacterium and colorectal cancer: causal factor or passenger? Results from a large colorectal cancer screening study. Carcinogenesis 38 781–788. 10.1093/carcin/bgx053 PubMed DOI

Arthur J. C., Jobin C. (2011). The struggle within: microbial influences on colorectal cancer. Inflamm. Bowel Dis. 17 396–409. 10.1002/ibd.21354 PubMed DOI PMC

Arthur J. C., Perez-Chanona E., Muhlbauer M., Tomkovich S., Uronis J. M., Fan T. J., et al. (2012). Intestinal inflammation targets cancer-inducing activity of the microbiota. Science 338 120–123. 10.1126/science.1224820 PubMed DOI PMC

Arumugam M., Raes J., Pelletier E., Le Paslier D., Yamada T., Mende D. R., et al. (2011). Enterotypes of the human gut microbiome. Nature 473 174–180. 10.1038/nature09944 PubMed DOI PMC

Backhed F., Fraser C. M., Ringel Y., Sanders M. E., Sartor R. B., Sherman P. M., et al. (2012). Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications. Cell Host Microbe 12 611–622. 10.1016/j.chom.2012.10.012 PubMed DOI

Bank S., Andersen P. S., Burisch J., Pedersen N., Roug S., Galsgaard J., et al. (2015). Polymorphisms in the toll-like receptor and the IL-23/IL-17 pathways were associated with susceptibility to inflammatory bowel disease in a danish cohort. PLoS One 10:e0145302. 10.1371/journal.pone.0145302 PubMed DOI PMC

Bankvall M., Sjoberg F., Gale G., Wold A., Jontell M., Ostman S. (2014). The oral microbiota of patients with recurrent aphthous stomatitis. J. Oral Microbiol. 6:25739. 10.3402/Jom.V6.25739 PubMed DOI PMC

Bartova J., Sommerova P., Lyuya-Mi Y., Mysak J., Prochazkova J., Duskova J., et al. (2014). Periodontitis as a risk factor of atherosclerosis. J. Immunol. Res. 2014:636893. 10.1155/2014/636893 PubMed DOI PMC

Blazkova H., Krejcikova K., Moudry P., Frisan T., Hodny Z., Bartek J. (2010). Bacterial intoxication evokes cellular senescence with persistent DNA damage and cytokine signalling. J. Cell Mol. Med. 14 357–367. 10.1111/j.1582-4934.2009.00862.x PubMed DOI PMC

Boursi B., Haynes K., Mamtani R., Yang Y. X. (2015). Impact of antibiotic exposure on the risk of colorectal cancer. Pharmacoepidemiol. Drug Saf. 24 534–542. 10.1002/pds.3765 PubMed DOI

Canabarro A., Valle C., Farias M. R., Santos F. B., Lazera M., Wanke B. (2013). Association of subgingival colonization of Candida albicans and other yeasts with severity of chronic periodontitis. J. Periodontal Res. 48 428–432. 10.1111/jre.12022 PubMed DOI

Carlsson J., Larsen J. T., Edlund M. B. (1993). Peptostreptococcus micros has a uniquely high capacity to form hydrogen sulfide from glutathione. Oral Microbiol. Immunol. 8 42–45. 10.1111/j.1399-302X.1993.tb00541.x PubMed DOI

Casarin R. C., Saito D., Santos V. R., Pimentel S. P., Duarte P. M., Casati M. Z., et al. (2012). Detection of Mogibacterium timidum in subgingival biofilm of aggressive and non-diabetic and diabetic chronic periodontitis patients. Braz. J. Microbiol. 43 931–937. 10.1590/S1517-838220120003000012 PubMed DOI PMC

Castellarin M., Warren R. L., Freeman J. D., Dreolini L., Krzywinski M., Strauss J., et al. (2012). Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 22 299–306. 10.1101/gr.126516.111 PubMed DOI PMC

Chehoud C., Albenberg L. G., Judge C., Hoffmann C., Grunberg S., Bittinger K., et al. (2015). Fungal signature in the gut microbiota of pediatric patients with inflammatory bowel disease. Inflamm. Bowel Dis. 21 1948–1956. 10.1097/MIB.0000000000000454 PubMed DOI PMC

Chenicheri S., Usha R., Ramachandran R., Thomas V., Wood A. (2017). Insight into oral biofilm: primary, secondary and residual caries and phyto-challenged solutions. Open Dent J. 11 312–333. 10.2174/1874210601711010312 PubMed DOI PMC

Claesson R., Edlund M. B., Persson S., Carlsson J. (1990). Production of volatile sulfur compounds by various Fusobacterium species. Oral Microbiol. Immunol. 5 137–142. 10.1111/j.1399-302X.1990.tb00411.x PubMed DOI

Cobb C. M., Kelly P. J., Williams K. B., Babbar S., Angolkar M., Derman R. J. (2017). The oral microbiome and adverse pregnancy outcomes. Int. J. Womens Health 9 551–559. 10.2147/Ijwh.S142730 PubMed DOI PMC

Costalonga M., Herzberg M. C. (2014). The oral microbiome and the immunobiology of periodontal disease and caries. Immunol. Lett. 162 22–38. 10.1016/j.imlet.2014.08.017 PubMed DOI PMC

da Silva E. S., Feres M., Figueiredo L. C., Shibli J. A., Ramiro F. S., Faveri M. (2014). Microbiological diversity of peri-implantitis biofilm by Sanger sequencing. Clin. Oral Implants Res. 25 1192–1199. 10.1111/clr.12231 PubMed DOI

Darveau R. P., Hajishengallis G., Curtis M. A. (2012). Porphyromonas gingivalis as a potential community activist for disease. J. Dent. Res. 91 816–820. 10.1177/0022034512453589 PubMed DOI PMC

De Ruyck K., De Boevre M., Huybrechts I., De Saeger S. (2015). Dietary mycotoxins, co-exposure, and carcinogenesis in humans: short review. Mutat. Res. Rev. Mutat. Res. 766 32–41. 10.1016/j.mrrev.2015.07.003 PubMed DOI

Dejea C. M., Wick E. C., Hechenbleikner E. M., White J. R., Mark Welch J. L., Rossetti B. J., et al. (2014). Microbiota organization is a distinct feature of proximal colorectal cancers. Proc. Natl. Acad. Sci. U.S.A. 111 18321–18326. 10.1073/pnas.1406199111 PubMed DOI PMC

Diaz P. I., Xie Z. H., Sobue T., Thompson A., Biyikoglu B., Ricker A., et al. (2012). Synergistic interaction between Candida albicans and commensal oral streptococci in a novel in vitro mucosal model. Infect. Immun. 80 620–632. 10.1128/Iai.05896-11 PubMed DOI PMC

Dupuy A. K., David M. S., Li L., Heider T. N., Peterson J. D., Montano E. A., et al. (2014). Redefining the human oral mycobiome with improved practices in amplicon-based taxonomy: discovery of malassezia as a prominent commensal. PLoS One 9:e90899. 10.1371/journal.pone.0090899 PubMed DOI PMC

Egeberg A., Mallbris L., Gislason G., Hansen P. R., Mrowietz U. (2017). Risk of periodontitis in patients with psoriasis and psoriatic arthritis. J. Eur. Acad. Dermatol. Venereol. 31 288–293. 10.1111/jdv.13814 PubMed DOI

El-Aouar R. A., Nicolas A., Castro T. L. D., Deplanche M., Azevedo V. A. D., Goossens P. L., et al. (2017). Heterogeneous family of cyclomodulins: smart weapons that allow bacteria to hijack the eukaryotic cell cycle and promote infections. Front. Cell Infect. Microbiol. 7:208 10.3389/Fcimb.2017.00364 PubMed DOI PMC

Eley B. M., Cox S. W. (2003). Proteolytic and hydrolytic enzymes from putative periodontal pathogens: characterization, molecular genetics, effects on host defenses and tissues and detection in gingival crevice fluid. Periodontol 31 105–124. 10.1034/j.1600-0757.2003.03107.x PubMed DOI

Fan X., Alekseyenko A. V., Wu J., Jacobs E. J., Gapstur S. M., Purdue M. P., et al. (2016). Human oral microbiome and prospective risk for pancreatic cancer: a population based, nested case control study. Cancer Res. 76:4350. 10.1158/1538-7445.AM2016-4350 PubMed DOI PMC

Ferlay J., Soerjomataram I., Dikshit R., Eser S., Mathers C., Rebelo M., et al. (2015). Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 136 E359–E386. 10.1002/ijc.29210 PubMed DOI

Flanagan L., Schmid J., Ebert M., Soucek P., Kunicka T., Liska V., et al. (2014). Fusobacterium nucleatum associates with stages of colorectal neoplasia development, colorectal cancer and disease outcome. Eur. J. Clin. Microbiol. Infect. Dis. 33 1381–1390. 10.1007/s10096-014-2081-3 PubMed DOI

Flemer B., Lynch D. B., Brown J. M., Jeffery I. B., Ryan F. J., Claesson M. J., et al. (2017). Tumour-associated and non-tumour-associated microbiota in colorectal cancer. Gut 66 633–643. 10.1136/gutjnl-2015-309595 PubMed DOI PMC

Ford P. J., Gemmell E., Chan A., Carter C. L., Walker P. J., Bird P. S., et al. (2006). Inflammation, heat shock proteins and periodontal pathogens in atherosclerosis: an immunohistologic study. Oral Microbiol. Immunol. 21 206–211. 10.1111/j.1399-302X.2006.00276.x PubMed DOI

Ford P. J., Gemmell E., Hamlet S. M., Hasan A., Walker P. J., West M. J., et al. (2005). Cross-reactivity of GroEL antibodies with human heat shock protein 60 and quantification of pathogens in atherosclerosis. Oral Microbiol. Immunol. 20 296–302. 10.1111/j.1399-302X.2005.00230.x PubMed DOI

Gagniere J., Raisch J., Veziant J., Barnich N., Bonnet R., Buc E., et al. (2016). Gut microbiota imbalance and colorectal cancer. World J. Gastroenterol. 22 501–518. 10.3748/wjg.v22.i2.501 PubMed DOI PMC

Ghannoum M. A., Jurevic R. J., Mukherjee P. K., Cui F., Sikaroodi M., Naqvi A., et al. (2010). Characterization of the oral fungal microbiome (Mycobiome) in healthy individuals. PLoS Pathog. 6:e1000713. 10.1371/journal.ppat.1000713 PubMed DOI PMC

Gill S. R., Pop M., DeBoy R. T., Eckburg P. B., Turnbaugh P. J., Samuel B. S., et al. (2006). Metagenomic analysis of the human distal gut microbiome. Science 312 1355–1359. 10.1126/science.1124234 PubMed DOI PMC

Gomes C. C., Guimarães L. S., Pinto L. C. C., Camargo G. A. D. C. G., Valente M. I. B., Sarquis M. I. M. (2017). Investigations of the prevalence and virulence of Candida albicans in periodontal and endodontic lesions in diabetic and normoglycemic patients. J. Appl. Oral Sci. 25 274–281. 10.1590/1678-7757-2016-0432 PubMed DOI PMC

Greenwald R. A., Kirkwood K. (1999). Adult periodontitis as a model for rheumatoid arthritis (with emphasis on treatment strategies). J. Rheumatol. 26 1650–1653. PubMed

Hajishengallis G., Korostoff J. M. (2017). Revisiting the page & schroeder model: the good, the bad and the unknowns in the periodontal host response 40 years later. Periodontol 75 116–151. 10.1111/prd.12181 PubMed DOI PMC

Hale V. L., Chen J., Johnson S., Harrington S. C., Yab T. C., Smyrk T. C., et al. (2017). Shifts in the fecal microbiota associated with adenomatous polyps. Cancer Epidemiol. Biomarkers Prev. 26 85–94. 10.1158/1055-9965.EPI-16-0337 PubMed DOI PMC

Han Y. W. (2015). Fusobacterium nucleatum: a commensal-turned pathogen. Curr. Opin. Microbiol. 23 141–147. 10.1016/j.mib.2014.11.013 PubMed DOI PMC

He J. Z., Li Y., Cao Y. P., Xue J., Zhou X. D. (2015). The oral microbiome diversity and its relation to human diseases. Folia Microbiol. 60 69–80. 10.1007/s12223-014-0342-2 PubMed DOI

Heijl L., Wennstrom J., Lindhe J., Socransky S. S. (1980). Periodontal-disease in gnotobiotic-rats. J. Periodontal Res. 15 405–419. 10.1111/j.1600-0765.1980.tb00298.x PubMed DOI

Hoffmann C., Dollive S., Grunberg S., Chen J., Li H., Wu G. D., et al. (2013). Archaea and fungi of the human gut microbiome: correlations with diet and bacterial residents. PLoS One 8:e66019. 10.1371/journal.pone.0066019 PubMed DOI PMC

Huffnagle G. B., Noverr M. C. (2013). The emerging world of the fungal microbiome. Trends Microbiol. 21 334–341. 10.1016/j.tim.2013.04.002 PubMed DOI PMC

Human Microbiome Project Consortium (2012). Structure, function and diversity of the healthy human microbiome. Nature 486 207–214. 10.1038/nature11234 PubMed DOI PMC

Huse S. M., Ye Y. Z., Zhou Y. J., Fodor A. A. (2012). A core human microbiome as viewed through 16S rRNA sequence clusters. PLoS One 7:e34242. 10.1371/journal.pone.0034242 PubMed DOI PMC

Huycke M. M., Abrams V., Moore D. R. (2002). Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis 23 529–536. 10.1093/carcin/23.3.529 PubMed DOI

Inaba H., Sugita H., Kuboniwa M., Iwai S., Hamada M., Noda T., et al. (2013). Porphyromonas gingivalis promotes invasion of oral squamous cell carcinoma through induction of proMMP9 and its activation. Cell Microbiol. 16 131–145. 10.1111/cmi.12211 PubMed DOI PMC

Ivanyi L., Newman H. N., Marsh P. D. (1991). T-cell proliferative responses to molecular fractions of periodontopathic bacteria. Clin. Exp. Immunol. 83 108–111. 10.1111/j.1365-2249.1991.tb05597.x PubMed DOI PMC

Johansson M. E., Larsson J. M., Hansson G. C. (2011). The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions. Proc. Natl. Acad. Sci. U.S.A. 108 4659–4665. 10.1073/pnas.1006451107 PubMed DOI PMC

Johansson M. E., Sjovall H., Hansson G. C. (2013). The gastrointestinal mucus system in health and disease. Nat. Rev. Gastroenterol. Hepatol. 10 352–361. 10.1038/nrgastro.2013.35 PubMed DOI PMC

Johnson C. H., Dejea C. M., Edler D., Hoang L. T., Santidrian A. F., Felding B. H., et al. (2015). Metabolism links bacterial biofilms and colon carcinogenesis. Cell Metab. 21 891–897. 10.1016/j.cmet.2015.04.011 PubMed DOI PMC

Kadowaki T., Nakayama K., Okamoto K., Abe N., Baba A., Shi Y. X., et al. (2000). Porphyromonas gingivalis proteinases as virulence determinants in progression of periodontal diseases. J. Biochem. 128 153–159. 10.1093/oxfordjournals.jbchem.a022735 PubMed DOI

Kaiko G. E., Ryu S. H., Koues O. I., Collins P. L., Solnica-Krezel L., Pearce E. J., et al. (2016). The colonic crypt protects stem cells from microbiota-derived metabolites. Cell 165 1708–1720. 10.1016/j.cell.2016.10.034 PubMed DOI PMC

Kasser U. R., Gleissner C., Dehne F., Michel A., Willershausen-Zonnchen B., Bolten W. W. (1997). Risk for periodontal disease in patients with longstanding rheumatoid arthritis. Arthritis Rheum. 40 2248–2251. 10.1002/art.1780401221 PubMed DOI

Khan S. H., Aguirre A., Bobek L. A. (1998). In-situ hybridization localized MUC7 mucin gene expression to the mucous acinar cells of human and MUC7-transgenic mouse salivary glands. Glycoconj. J. 15 1125–1132. 10.1023/A:1006955604501 PubMed DOI

Kilian M., Mestecky J., Russell M. W. (1988). Defense mechanisms involving Fc-dependent functions of immunoglobulin A and their subversion by bacterial immunoglobulin A proteases. Microbiol. Rev. 52 296–303. PubMed PMC

Kilian M., Reinholdt J., Nyvad B., Frandsen E. V., Mikkelsen L. (1989). IgA1 proteases of oral streptococci: ecological aspects. Immunol. Invest. 18 161–170. 10.3109/08820138909112235 PubMed DOI

Kim Y. J., Choi Y. S., Baek K. J., Yoon S. H., Park H. K., Choi Y. (2016). Mucosal and salivary microbiota associated with recurrent aphthous stomatitis. BMC Microbiol. 16:57. 10.1186/s12866-016-0673-z PubMed DOI PMC

Kinane D. F., Stathopoulou P. G., Papapanou P. N. (2017). Periodontal diseases. Nat. Rev. Dis. Primers 3:17038. 10.1038/Nrdp.2017.38 PubMed DOI

Klimesova K., Kverka M., Zakostelska Z., Hudcovic T., Hrncir T., Stepankova R., et al. (2013). Altered gut microbiota promotes colitis-associated cancer in IL-1 receptor-associated kinase M-deficient mice. Inflamm. Bowel Dis. 19 1266–1277. 10.1097/MIB.0b013e318281330a PubMed DOI PMC

Kostic A. D., Chun E. Y., Robertson L., Glickman J. N., Gallini C. A., Michaud M., et al. (2013). Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe 14 207–215. 10.1016/j.chom.2013.07.007 PubMed DOI PMC

Kostic A. D., Gevers D., Pedamallu C. S., Michaud M., Duke F., Earl A. M., et al. (2012). Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res. 22 292–298. 10.1101/gr.126573.111 PubMed DOI PMC

Li S., Konstantinov S. R., Smits R., Peppelenbosch M. P. (2017). Bacterial biofilms in colorectal cancer initiation and progression. Trends Mol. Med. 23 18–30. 10.1016/j.molmed.2016.11.004 PubMed DOI

Liang Q., Chiu J., Chen Y., Huang Y., Higashimori A., Fang J., et al. (2017). Fecal bacteria act as novel biomarkers for noninvasive diagnosis of colorectal cancer. Clin. Cancer Res. 23 2061–2070. 10.1158/1078-0432.CCR-16-1599 PubMed DOI

Liguori G., Lamas B., Richard M. L., Brandi G., da Costa G., Hoffmann T. W., et al. (2016). Fungal dysbiosis in mucosa-associated microbiota of crohn’s disease patients. J. Crohns Colitis 10 296–305. 10.1093/ecco-jcc/jjv209 PubMed DOI PMC

Louis P., Young P., Holtrop G., Flint H. J. (2010). Diversity of human colonic butyrate-producing bacteria revealed by analysis of the butyryl-CoA: acetate CoA-transferase gene. Environ. Microbiol. 12 304–314. 10.1111/j.1462-2920.2009.02066.x PubMed DOI

Lu Y., Chen J., Zheng J., Hu G., Wang J., Huang C., et al. (2016). Mucosal adherent bacterial dysbiosis in patients with colorectal adenomas. Sci. Rep. 6:26337. 10.1038/srep26337 PubMed DOI PMC

Luan C., Xie L., Yang X., Miao H., Lv N., Zhang R., et al. (2015). Dysbiosis of fungal microbiota in the intestinal mucosa of patients with colorectal adenomas. Sci. Rep. 5:7980. 10.1038/srep07980 PubMed DOI PMC

Macfarlane G. T., Macfarlane S. (2012). Bacteria, colonic fermentation, and gastrointestinal health. J. AOAC Int. 95 50–60. 10.5740/jaoacint.SGE_Macfarlane PubMed DOI

Maffei V. J., Kim S., Blanchard E., Luo M., Jazwinski S. M., Taylor C. M., et al. (2017). Biological aging and the human gut microbiota. J. Gerontol. A Biol. Sci. Med. Sci. 72 1474–1482. 10.1093/gerona/glx042 PubMed DOI PMC

Mager D. L., Ximenez-Fyvie L. A., Haffajee A. D., Socransky S. S. (2003). Distribution of selected bacterial species on intraoral surfaces. J. Clin. Periodontol. 30 644–654. 10.1034/j.1600-051X.2003.00376.x PubMed DOI

Mao S., Park Y., Hasegawa Y., Tribble G. D., James C. E., Handfield M., et al. (2007). Intrinsic apoptotic pathways of gingival epithelial cells modulated by Porphyromonas gingivalis. Cell Microbiol. 9 1997–2007. 10.1111/j.1462-5822.2007.00931.x PubMed DOI PMC

Marchesan J., Jiao Y., Schaff R. A., Hao J., Morelli T., Kinney J. S., et al. (2016). TLR4, NOD1 and NOD2 mediate immune recognition of putative newly identified periodontal pathogens. Mol. Oral Microbiol. 31 243–258. 10.1111/omi.12116 PubMed DOI PMC

Marcotte H., Lavoie M. C. (1998). Oral microbial ecology and the role of salivary immunoglobulin A. Microbiol. Mol. Biol. Rev. 62 71–109. PubMed PMC

Maresca M., Fantini J. (2010). Some food-associated mycotoxins as potential risk factors in humans predisposed to chronic intestinal inflammatory diseases. Toxicon 56 282–294. 10.1016/j.toxicon.2010.04.016 PubMed DOI

Mehta R. S., Nishihara R., Cao Y., Song M., Mima K., Qian Z. R., et al. (2017). Association of dietary patterns with risk of colorectal cancer subtypes classified by Fusobacterium nucleatum in tumor tissue. JAMA Oncol. 3 921–927. 10.1001/jamaoncol.2016.6374 PubMed DOI PMC

Miraglia A. G., Travaglione S., Meschini S., Falzano L., Matarrese P., Quaranta M. G., et al. (2007). Cytotoxic necrotizing factor 1 prevents apoptosis via the Akt/IkappaB kinase pathway: role of nuclear factor-kappaB and Bcl-2. Mol. Biol. Cell 18 2735–2744. 10.1091/mbc.E06-10-0910 PubMed DOI PMC

Momen-Heravi F., Babic A., Tworoger S. S., Zhang L., Wu K., Smith-Warner S. A., et al. (2017). Periodontal disease, tooth loss and colorectal cancer risk: results from the Nurses’ Health Study. Int. J. Cancer 140 646–652. 10.1002/ijc.30486 PubMed DOI PMC

Mukherjee P. K., Chandra J., Retuerto M., Sikaroodi M., Brown R. E., Jurevic R., et al. (2014). Oral mycobiome analysis of HIV-infected patients: identification of Pichia as an antagonist of opportunistic fungi. PLoS Pathog. 10:e1003996. 10.1371/journal.ppat.1003996 PubMed DOI PMC

Nagano Y., Elborn J. S., Miller B. C., Walker J. M., Goldsmith C. E., Rendall J., et al. (2010). Comparison of techniques to examine the diversity of fungi in adult patients with cystic fibrosis. Med. Mycol. 48 166–176. 10.3109/13693780903127506 PubMed DOI

Nakatsu G., Li X. C., Zhou H. K., Sheng J. Q., Wong S. H., Wu W. K. K., et al. (2015). Gut mucosal microbiome across stages of colorectal carcinogenesis. Nat. Commun. 6:8727. 10.1038/Ncomms9727 PubMed DOI PMC

Nordman H., Davies J. R., Lindell G., de Bolos C., Real F., Carlstedt I. (2002). Gastric MUC5AC and MUC6 are large oligomeric mucins that differ in size, glycosylation and tissue distribution. Biochem. J. 364 191–200. 10.1042/bj3640191 PubMed DOI PMC

Nougayrede J. P., Homburg S., Taieb F., Boury M., Brzuszkiewicz E., Gottschalk G., et al. (2006). Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science 313 848–851. 10.1126/science.1127059 PubMed DOI

Papadopoulos G., Weinberg E. O., Massari P., Gibson F. C., III, Wetzler L. M., Morgan E. F., et al. (2013). Macrophage-specific TLR2 signaling mediates pathogen-induced TNF-dependent inflammatory oral bone loss. J. Immunol. 190 1148–1157. 10.4049/jimmunol.1202511 PubMed DOI PMC

Park H. E., Kim J. H., Cho N. Y., Lee H. S., Kang G. H. (2017). Intratumoral Fusobacterium nucleatum abundance correlates with macrophage infiltration and CDKN2A methylation in microsatellite-unstable colorectal carcinoma. Virchows Arch. 471 329–336. 10.1007/s00428-017-2171-6 PubMed DOI

Persson S., Edlund M. B., Claesson R., Carlsson J. (1990). The formation of hydrogen sulfide and methyl mercaptan by oral bacteria. Oral Microbiol. Immunol. 5 195–201. 10.1111/j.1399-302X.1990.tb00645.x PubMed DOI

Peters B. A., Dominianni C., Shapiro J. A., Church T. R., Wu J., Miller G., et al. (2016). The gut microbiota in conventional and serrated precursors of colorectal cancer. Microbiome 4:69. 10.1186/s40168-016-0218-6 PubMed DOI PMC

Peters B. A., Wu J., Hayes R. B., Ahn J. (2017). The oral fungal mycobiome: characteristics and relation to periodontitis in a pilot study. BMC Microbiol. 17:157. 10.1186/s12866-017-1064-9 PubMed DOI PMC

Pitts N. B., Zero D. T., Marsh P. D., Ekstrand K., Weintraub J. A., Ramos-Gomez F., et al. (2017). Dental caries. Nat. Rev. Dis. Primers 3:17030. 10.1038/nrdp.2017.30 PubMed DOI

Potempa J., Sroka A., Imamura T., Travis J. (2003). Gingipains, the major cysteine proteinases and virulence factors of Porphyromonas gingivalis: structure, function and assembly of multidomain protein complexes. Curr. Protein Pept. Sci. 4 397–407. 10.2174/1389203033487036 PubMed DOI

Potgieter M., Bester J., Kell D. B., Pretorius E. (2015). The dormant blood microbiome in chronic, inflammatory diseases. FEMS Microbiol. Rev. 39 567–591. 10.1093/femsre/fuv013 PubMed DOI PMC

Proctor D. M., Relman D. A. (2017). The landscape ecology and microbiota of the human nose, mouth, and throat. Cell Host Microbe 21 421–432. 10.1016/j.chom.2017.03.011 PubMed DOI PMC

Qin J., Li R., Raes J., Arumugam M., Burgdorf K. S., Manichanh C., et al. (2010). A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464 59–65. 10.1038/nature08821 PubMed DOI PMC

Raisch J., Buc E., Bonnet M., Sauvanet P., Vazeille E., de Vallee A., et al. (2014). Colon cancer-associated B2 Escherichia coli colonize gut mucosa and promote cell proliferation. World J. Gastroenterol. 20 6560–6572. 10.3748/wjg.v20.i21.6560 PubMed DOI PMC

Reddy B. S., Narisawa T., Maronpot R., Weisburger J. H., Wynder E. L. (1975). Animal models for the study of dietary factors and cancer of the large bowel. Cancer Res. 35 3421–3426. PubMed

Roberts F. A., Darveau R. P. (2015). Microbial protection and virulence in periodontal tissue as a function of polymicrobial communities: symbiosis and dysbiosis. Periodontol 69 18–27. 10.1111/prd.12087 PubMed DOI PMC

Robinson C. J., Bohannan B. J. M., Young V. B. (2010). From structure to function: the ecology of host-associated microbial communities. Microbiol. Mol. Biol. R 74 453–476. 10.1128/Mmbr.00014-10 PubMed DOI PMC

Rubinstein M. R., Wang X., Liu W., Hao Y., Cai G., Han Y. W. (2013). Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/beta-catenin signaling via its FadA adhesin. Cell Host Microbe 14 195–206. 10.1016/j.chom.2013.07.012 PubMed DOI PMC

Sartor R. B. (2008). Microbial influences in inflammatory bowel diseases. Gastroenterology 134 577–594. 10.1053/j.gastro.2007.11.059 PubMed DOI

Saunders C. W., Scheynius A., Heitman J. (2012). Malassezia fungi are specialized to live on skin and associated with dandruff, eczema, and other skin diseases. PLoS Pathog. 8:e1002701. 10.1371/journal.ppat.1002701 PubMed DOI PMC

Segata N., Haake S. K., Mannon P., Lemon K. P., Waldron L., Gevers D., et al. (2012). Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples. Genome Biol. 13:R42. 10.1186/gb-2012-13-6-r42 PubMed DOI PMC

Shen X. J., Rawls J. F., Randall T., Burcal L., Mpande C. N., Jenkins N., et al. (2010). Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas. Gut Microbes 1 138–147. 10.4161/gmic.1.3.12360 PubMed DOI PMC

Slots J. (1976). Predominant cultivable organisms in juvenile periodontitis. Scand. J. Dent. Res. 84 1–10. 10.1111/j.1600-0722.1976.tb00454.x PubMed DOI

Socransky S. S., Haffajee A. D. (2002). Dental biofilms: difficult therapeutic targets. Periodontol 28 12–55. 10.1034/j.1600-0757.2002.280102.x PubMed DOI

Socransky S. S., Haffajee A. D. (2005). Periodontal microbial ecology. Periodontol 38 135–187. 10.1111/j.1600-0757.2005.00107.x PubMed DOI

Socransky S. S., Haffajee A. D., Cugini M. A., Smith C., Kent R. L. (1998). Microbial complexes in subgingival plaque. J. Clin. Periodontol. 25 134–144. 10.1111/j.1600-051X.1998.tb02419.x PubMed DOI

Sokol H., Leducq V., Aschard H., Pham H. P., Jegou S., Landman C., et al. (2017). Fungal microbiota dysbiosis in IBD. Gut 66 1039–1048. 10.1136/gutjnl-2015-310746 PubMed DOI PMC

Sousa E. L., Martinho F. C., Leite F. R., Nascimento G. G., Gomes B. P. (2014). Macrophage cell activation with acute apical abscess contents determined by interleukin-1 Beta and tumor necrosis factor alpha production. J. Endod. 40 1752–1757. 10.1016/j.joen.2014.06.019 PubMed DOI

Stecher B., Hardt W. D. (2011). Mechanisms controlling pathogen colonization of the gut. Curr. Opin. Microbiol. 14 82–91. 10.1016/j.mib.2010.10.003 PubMed DOI

Swidsinski A., Khilkin M., Kerjaschki D., Schreiber S., Ortner M., Weber J. et al. (1998). Association between intraepithelial Escherichia coli and colorectal cancer. Gastroenterology 115 281–286. 10.1016/S0016-5085(98)70194-5 PubMed DOI

Taieb F., Nougayrede J. P., Watrin C., Samba-Louaka A., Oswald E. (2006). Escherichia coli cyclomodulin Cif induces G2 arrest of the host cell cycle without activation of the DNA-damage checkpoint-signalling pathway. Cell Microbiol. 8 1910–1921. 10.1111/j.1462-5822.2006.00757.x PubMed DOI

Teles R., Teles F., Frias-Lopez J., Paster B., Haffajee A. (2013). Lessons learned and unlearned in periodontal microbiology. Periodontol 62 95–162. 10.1111/prd.12010 PubMed DOI PMC

Temoin S., Chakaki A., Askari A., El-Halaby A., Fitzgerald S., Marcus R. E., et al. (2012). Identification of oral bacterial DNA in synovial fluid of patients with arthritis with native and failed prosthetic joints. J. Clin. Rheumatol. 18 117–121. 10.1097/RHU.0b013e3182500c95 PubMed DOI PMC

Tjalsma H., Boleij A., Marchesi J. R., Dutilh B. E. (2012). A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects. Nat. Rev. Microbiol. 10 575–582. 10.1038/nrmicro2819 PubMed DOI

Tlaskalova-Hogenova H., Stepankova R., Hudcovic T., Tuckova L., Cukrowska B., Lodinova-Zadnikova R., et al. (2004). Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol. Lett. 93 97–108. 10.1016/j.imlet.2004.02.005 PubMed DOI

Tlaskalova-Hogenova H., Vannucci L., Klimesova K., Stepankova R., Krizan J., Kverka M. (2014). Microbiome and colorectal carcinoma: insights from germ-free and conventional animal models. Cancer J. 20 217–224. 10.1097/PPO.0000000000000052 PubMed DOI

Tomas I., Diz P., Tobias A., Scully C., Donos N. (2012). Periodontal health status and bacteraemia from daily oral activities: systematic review/meta-analysis. J. Clin. Periodontol. 39 213–228. 10.1111/j.1600-051X.2011.01784.x PubMed DOI

Toprak N. U., Yagci A., Gulluoglu B. M., Akin M. L., Demirkalem P., Celenk T., et al. (2006). A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer. Clin. Microbiol. Infect. 12 782–786. 10.1111/j.1469-0691.2006.01494.x PubMed DOI

Trojanowska D., Zwolinska-Wcislo M., Tokarczyk M., Kosowski K., Mach T., Budak A. (2010). The role of Candida in inflammatory bowel disease. Estimation of transmission of C. albicans fungi in gastrointestinal tract based on genetic affinity between strains. Med. Sci. Monit. 16 Cr451–Cr457. PubMed

Tsoi H., Chu E. S. H., Zhang X., Sheng J., Nakatsu G., Ng S. C., et al. (2017). Peptostreptococcus anaerobius induces intracellular cholesterol biosynthesis in colon cells to induce proliferation and causes dysplasia in mice. Gastroenterology 152 1419–1433. 10.1053/j.gastro.2017.01.009 PubMed DOI

Underhill D. M., Iliev I. D. (2014). The mycobiota: interactions between commensal fungi and the host immune system. Nat. Rev. Immunol. 14 405–416. 10.1038/nri3684 PubMed DOI PMC

Ungprasert P., Wijarnpreecha K., Wetter D. A. (2017). Periodontitis and risk of psoriasis: a systematic review and meta-analysis. J. Eur. Acad. Dermatol. Venereol. 31 857–862. 10.1111/jdv.14051 PubMed DOI PMC

Urzúa B., Hermosilla G., Gamonal J., Morales-Bozo I., Canals M., Barahona S., et al. (2008). Yeast diversity in the oral microbiota of subjects with periodontitis: Candida albicans and Candida dubliniensis colonize the periodontal pockets. Med. Mycol. 46 783–793. 10.1080/13693780802060899 PubMed DOI

Vannucci L., Stepankova R., Kozakova H., Fiserova A., Rossmann P., Tlaskalova-Hogenova H. (2008). Colorectal carcinogenesis in germ-free and conventionally reared rats: different intestinal environments affect the systemic immunity. Int. J. Oncol. 32 609–617. 10.3892/ijo.32.3.609 PubMed DOI

Wade W. G. (2013). The oral microbiome in health and disease. Pharmacol. Res. 69 137–143. 10.1016/j.phrs.2012.11.006 PubMed DOI

Walker A. W., Ince J., Duncan S. H., Webster L. M., Holtrop G., Ze X., et al. (2011). Dominant and diet-responsive groups of bacteria within the human colonic microbiota. ISME J. 5 220–230. 10.1038/ismej.2010.118 PubMed DOI PMC

Wickstrom C., Davies J. R., Eriksen G. V., Veerman E. C., Carlstedt I. (1998). MUC5B is a major gel-forming, oligomeric mucin from human salivary gland, respiratory tract and endocervix: identification of glycoforms and C-terminal cleavage. Biochem. J. 334(Pt 3), 685–693. 10.1042/bj3340685 PubMed DOI PMC

Wong B. K., McGregor N. R., Butt H. L., Knight R., Liu L. Y., Darby I. B. (2016). Association of clinical parameters with periodontal bacterial haemolytic activity. J. Clin. Periodontol. 43 503–511. 10.1111/jcpe.12554 PubMed DOI

Wu G. D., Chen J., Hoffmann C., Bittinger K., Chen Y. Y., Keilbaugh S. A., et al. (2011). Linking long-term dietary patterns with gut microbial enterotypes. Science 334 105–108. 10.1126/science.1208344 PubMed DOI PMC

Yamaoka Y., Suehiro Y., Hashimoto S., Hoshida T., Fujimoto M., Watanabe M., et al. (2017). Fusobacterium nucleatum as a prognostic marker of colorectal cancer in a Japanese population. J. Gastroenterol. 53 517–524. 10.1007/s00535-017-1382-6 PubMed DOI

Yu T. C., Guo F. F., Yu Y. N., Sun T. T., Ma D., Han J. X.et al. (2017). Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell 170 548–563. 10.1016/j.cell.2017.07.008e16 PubMed DOI PMC

Zanzoni A., Spinelli L., Braham S., Brun C. (2017). Perturbed human sub-networks by Fusobacterium nucleatum candidate virulence proteins. Microbiome 5:89. 10.1186/s40168-017-0307-1 PubMed DOI PMC

Zhou Y. J., Gao H. Y., Mihindukulasuriya K. A., La Rosa P. S., Wylie K. M., Vishnivetskaya T., et al. (2013). Biogeography of the ecosystems of the healthy human body. Genome Biol. 14:R1. 10.1186/Gb-2013-14-1-R1 PubMed DOI PMC

Fungal Gut Microbiota Dysbiosis and Its Role in Colorectal, Oral, and Pancreatic Carcinogenesis

Oxidative Damage in Sporadic Colorectal Cancer: Molecular Mapping of Base Excision Repair Glycosylases in Colorectal Cancer Patients

Oral Microbiota Composition and Antimicrobial Antibody Response in Patients with Recurrent Aphthous Stomatitis

Diet Rich in Animal Protein Promotes Pro-inflammatory Macrophage Response and Exacerbates Colitis in Mice