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01-03-2020 | Crohn's Disease | Host Parasite Interactions in Periodontal Disease (C Genco and D Kinane, Section Editors)

The Periodontal Microenvironment: a Potential Reservoir for Intestinal Pathobionts in Crohn’s Disease

Authors: Jiho Sohn, Yijun Sun, Robert J. Genco, Keith L. Kirkwood

Published in: Current Oral Health Reports | Issue 1/2020

Abstract

Purpose of Review

Periodontal disease is a common bacteria-initiated inflammatory disease generating alveolar bone destruction around the dentition. Chronic periodontitis leads to the formation of a nutrient-rich periodontal microenvironment where opportunistic pathogens can thrive and flourish. The dissemination of these microbes from the oral cavity to other body sites can initiate or exacerbate disease, especially in susceptible individuals. This brief review will highlight the oral-gut axis and common bacterial etiologies associated with periodontal disease and Crohn’s disease as well as providing a perspective for future studies in this active area of investigation.

Recent Findings

Recent studies have indicated that there is an extensive transmission of oral bacteria along the gastrointestinal tract, suggesting the role of oral microbiota in intestinal pathologies. The presence of oral bacteria in the intestine strongly correlates with the severity of Crohn’s disease, one of the major types of inflammatory bowel disease. Periodontal disease is highly prevalent in Crohn’s disease, and the oral-gut microbiota transmission may be the mechanistic factor linking the two diseases.

Summary

A better understanding of the relationship between periodontal disease and Crohn’s disease may help define new therapeutic targets for the management of Crohn’s disease.

Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner AC, Yu WH, et al. The human oral microbiome. J Bacteriol. 2010;192:5002–17. https://doi.org/10.1128/JB.00542-10.CrossRefPubMedPubMedCentral

He XS, Shi WY. Oral microbiology: past, present and future. Int J Oral Sci. 2009;1:47–58. https://doi.org/10.4248/ijos.09029.CrossRefPubMedPubMedCentral

Struzycka I. The oral microbiome in dental caries. Pol J Microbiol. 2014;63:127–35. https://doi.org/10.33073/pjm-2014-018.CrossRefPubMed

Huang S, et al. Preliminary characterization of the oral microbiota of Chinese adults with and without gingivitis. BMC Oral Health. 2011;11. https://doi.org/10.1186/1472-6831-11-33.

Hajishengallis G, Liang S, Payne MA, Hashim A, Jotwani R, Eskan MA, et al. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe. 2011;10:497–506. https://doi.org/10.1016/j.chom.2011.10.006.CrossRef

Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med. 2015;21:895–905. https://doi.org/10.1038/nm.3914.CrossRefPubMed

Flemer, B. et al. The oral microbiota in colorectal cancer is distinctive and predictive. Gut gutjnl-2017-314814 (2017). https://doi.org/10.1136/gutjnl-2017-314814 CrossRefPubMed

Atarashi, K. et al. Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation. Science,(2017) 365(80-. ) 359–365 . This work demonstrated via gnotobiotic mice that Klebsiella of oral origin can colonize the gut and induce TH1 cell induction, DOI: https://doi.org/10.1126/science.aan4526.

Baumgart DC, Sandborn WJ. Crohn’s disease. Lancet. 2012;380:1590–605. https://doi.org/10.1016/S0140-6736(12)60026-9.CrossRefPubMed

10.

Ng SC, et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet. 2017;390:2769–78. https://doi.org/10.1016/S0140-6736(17)32448-0.CrossRefPubMed

11.

Polito JM, et al. Crohn’s disease: influence of age at diagnosis on site and clinical type of disease. Gastroenterology. 1996;111:580–6. https://doi.org/10.1053/gast.1996.v111.pm8780560.CrossRefPubMed

12.

Taleban S, Colombel JF, Mohler MJ, Fain MJ. Inflammatory bowel disease and the elderly: a review. J Crohn's Colitis. 2015;9:507–15. https://doi.org/10.1093/ecco-jcc/jjv059.CrossRef

13.

Rutgeerts P, et al. Effect of faecal stream diversion on recurrence of Crohn’s disease in the neoterminal ileum. Lancet. 1991;338:771–4. https://doi.org/10.1016/0140-6736(91)90663-A.CrossRefPubMed

14.

Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Prim. 2017;3:17038.CrossRefPubMed

15.

Eke PI. Update on prevalence of periodontitis in adults in the United States: NHANES 2009-2012. J Peridontology. 2015;86:611–22.CrossRef

16.

Larsen T, Fiehn NE. Dental biofilm infections – an update. Apmis. 2017;125:376–84. https://doi.org/10.1111/apm.12688.CrossRefPubMed

17.

Vieira Colombo AP, Magalhães CB, Hartenbach FARR, Martins do Souto R, Maciel da Silva-Boghossian C. Periodontal-disease-associated biofilm: a reservoir for pathogens of medical importance. Microb Pathog. 2015;94:27–34.CrossRefPubMed

18.

Diaz PI, Hoare A, Hong B-Y. Subgingival microbiome shifts and community dynamics in periodontal diseases. J Calif Dent Assoc. 2016;44:421–35.PubMed

19.

Scannapieco FA, Papandonatos GD, Dunford RG. Associations between oral conditions and respiratory disease in a national sample survey population. Ann Periodontol. 1998;3:251–6. https://doi.org/10.1902/annals.1998.3.1.251.CrossRefPubMed

20.

Genco R, Offenbacher S, Beck J. Periodontal disease and cardiovascular disease: epidemiology and possible mechanisms. J Am Dent Assoc. 2002;133(Suppl):14S–22S.CrossRefPubMed

21.

Beck J, Garcia R, Heiss G, Vokonas PS, Offenbacher S. Periodontal disease and cardiovascular disease. J Periodontol. 1996;67:1123–37. https://doi.org/10.1902/jop.1996.67.10s.1123.CrossRefPubMed

22.

Grossi SG, Genco RJ. Periodontal disease and diabetes mellitus: a two-way relationship. Ann Periodontol. 1998;3:51–61. https://doi.org/10.1902/annals.1998.3.1.51.CrossRefPubMed

23.

Leech MT, Bartold PM. The association between rheumatoid arthritis and periodontitis. Best Pract Res Clin Rheumatol. 2015;29:189–201. https://doi.org/10.1016/j.berh.2015.03.001.CrossRefPubMed

24.

Momen-Heravi F, Babic A, Tworoger SS, Zhang L, Wu K, Smith-Warner SA, et al. Periodontal disease, tooth loss and colorectal cancer risk: results from the nurses’ health study. Int J Cancer. 2017;140:646–52. https://doi.org/10.1002/ijc.30486.CrossRefPubMedPubMedCentral

25.

Brito F, de Barros FC, Zaltman C, Carvalho AT, Carneiro AJ, Fischer RG, et al. Prevalence of periodontitis and DMFT index in patients with Crohn’s disease and ulcerative colitis. J Clin Periodontol. 2008;35:555–60. https://doi.org/10.1111/j.1600-051X.2008.01231.x.CrossRefPubMed

26.

Yu HC, Chen TP, Chang YC. Inflammatory bowel disease as a risk factor for periodontitis under Taiwanese National Health Insurance Research database. J Dent Sci. 2018:1–6. https://doi.org/10.1016/j.jds.2018.03.004.CrossRefPubMedPubMedCentral

27.

Vavricka SR, Manser CN, Hediger S, Vögelin M, Scharl M, Biedermann L, et al. Periodontitis and gingivitis in inflammatory bowel disease: a case-control study. Inflamm Bowel Dis. 2013;19:2768–77. https://doi.org/10.1097/01.MIB.0000438356.84263.3b.CrossRefPubMed

28.

Habashneh RA, Khader YS, Alhumouz MK, Jadallah K, Ajlouni Y. The association between inflammatory bowel disease and periodontitis among Jordanians: a case-control study. J Periodontal Res. 2012;47:293–8. https://doi.org/10.1111/j.1600-0765.2011.01431.x.CrossRefPubMed

29.

Koutsochristou V, Zellos A, Dimakou K, Panayotou I, Siahanidou S, Roma-Giannikou E, et al. Dental caries and periodontal disease in children and adolescents with inflammatory bowel disease: a case-control study. Inflamm Bowel Dis. 2015;21:1839–46. https://doi.org/10.1097/MIB.0000000000000452.CrossRefPubMed

30.

Stein JM, Lammert F, Zimmer V, Granzow M, Reichert S, Schulz S, et al. Clinical periodontal and microbiologic parameters in patients with Crohn’s disease with consideration of the CARD15 genotype. J Periodontol. 2010;81:535–45. https://doi.org/10.1902/jop.2009.090563.CrossRefPubMed

31.

Papageorgiou SN, Hagner M, Nogueira AV, Franke A, Jäger A, Deschner J. Inflammatory bowel disease and oral health: systematic review and a meta-analysis. J Clin Periodontol. 2017;44:382–93. https://doi.org/10.1111/jcpe.12698.CrossRefPubMed

32.

Teeuw WJ, Gerdes VEA, Loos BG. Effect of periodontal treatment on glycemic control of diabetic patients: a systematic review and meta-analysis. Diabetes Care. 2010;33:421–7. https://doi.org/10.2337/dc09-1378.CrossRefPubMedPubMedCentral

33.

Ortiz P, Bissada NF, Palomo L, Han YW, al-Zahrani MS, Panneerselvam A, et al. Periodontal therapy reduces the severity of active rheumatoid arthritis in patients treated with or without tumor necrosis factor inhibitors. J Periodontol. 2009;80:535–40. https://doi.org/10.1902/jop.2009.080447.CrossRefPubMedPubMedCentral

34.

35.

Pietropaoli D, del Pinto R, Corridoni D, Rodriguez-Palacios A, di Stefano G, Monaco A, et al. Occurrence of spontaneous periodontal disease in the SAMP1/YitFc murine model of Crohn disease. J Periodontol. 2014;85:1799–805. https://doi.org/10.1902/jop.2014.140316.CrossRefPubMedPubMedCentral

36.

Sasaki H, et al. T cell response mediated by myeloid cell-derived IL-12 is responsible for Porphyromonas gingivalis -induced periodontitis in IL-10-deficient mice. J Immunol. 2008;180:6193–8. https://doi.org/10.4049/jimmunol.180.9.6193.CrossRefPubMed

37.

de Foureaux R, C, et al. Effects of probiotic therapy on metabolic and inflammatory parameters of rats with ligature-induced periodontitis associated with restraint stress. J Periodontol. 2014;85:975–83. https://doi.org/10.1902/jop.2013.130356.CrossRef

38.

Messora MR, et al. Probiotic therapy reduces periodontal tissue destruction and improves the intestinal morphology in rats with ligature-induced periodontitis. J Periodontol. 2013;84:1818–26. https://doi.org/10.1902/jop.2013.120644.CrossRefPubMed

39.

Arimatsu K, et al. Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota. Sci Rep. 2014;4:1–9.

40.

Nakajima M, et al. Oral administration of P. gingivalis induces dysbiosis of gut microbiota and impaired barrier function leading to dissemination of enterobacteria to the liver. PLoS One. 2015;10:1–15.

41.

Glick M. The oral-systemic health connection. A Guid to Patient Care. 2014.

42.

Zhu H, Hart CA, Sales D, Roberts NB. Bacterial killing in gastric juice - effect of pH and pepsin on Escherichia coli and Helicobacter pylori. J Med Microbiol. 2006;55:1265–70. https://doi.org/10.1099/jmm.0.46611-0.CrossRefPubMed

43.

Schubert ML, Peura DA. Control of gastric acid secretion in health and disease. Gastroenterology. 2008;134:1842–60. https://doi.org/10.1053/j.gastro.2008.05.021.CrossRefPubMed

44.

Schmidt, T. S. B. et al. Extensive transmission of microbes along the gastrointestinal tract. (2019). This work used large DNA shotgut sequencing data from human saliva and stool samples and showed that there is extensive oral-gut microbiota transmission in healthy individuals, DOI: https://doi.org/10.1016/j.pedn.2020.01.002.

45.

Lenz K, Buder R, Firlinger F, Lohr G, Voglmayr M. Effect of proton pump inhibitors on gastric pH in patients exposed to severe stress. Wien Klin Wochenschr. 2015;127:51–6. https://doi.org/10.1007/s00508-014-0637-y.CrossRefPubMed

46.

Corleto VD, Festa S, Di Giulio E, Annibale B. Proton pump inhibitor therapy and potential long-term harm. Curr Opin Endocrinol Diabetes Obes. 2014;21:3–8. https://doi.org/10.1097/MED.0000000000000031.CrossRefPubMed

47.

Hofmann AF, Eckmann L. How bile acids confer gut mucosal protection against bacteria. Proc Natl Acad Sci U S A. 2006;103:4333–4.CrossRefPubMedPubMedCentral

48.

Staels B, Fonseca VA. Bile acids and metabolic regulation: mechanisms and clinical responses to bile acid sequestration. Diabetes Care. 2009;32(Suppl 2).CrossRefPubMedPubMedCentral

49.

Lapidus A, Einarsson K. Effects of ileal resection on biliary lipids and bile acid composition in patients with Crohn’s disease. Gut. 1991;32:1488–91. https://doi.org/10.1136/gut.32.12.1488.CrossRefPubMedPubMedCentral

50.

Cho I, Blaser MJ. The human microbiome: at the interface of health and disease. Nat Rev Genet. 2012;13:260–70. https://doi.org/10.1038/nrg3182.CrossRefPubMedPubMedCentral

51.

Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature. 2012;489:220–30. https://doi.org/10.1038/nature11550.CrossRefPubMedPubMedCentral

52.

Pickard JM, Zeng MY, Caruso R, Núñez G. Gut microbiota: role in pathogen colonization, immune responses, and inflammatory disease. Immunol Rev. 2017;279:70–89. https://doi.org/10.1111/imr.12567.CrossRefPubMedPubMedCentral

53.

Segata N, et al. Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples. Genome Biol. 2012;13. https://doi.org/10.1186/gb-2012-13-6-r42.CrossRefPubMedPubMedCentral

54.

Olsen I, Yamazaki K. Can oral bacteria affect the microbiome of the gut? J Oral Microbiol. 2019;11. https://doi.org/10.1080/20002297.2019.1586422.CrossRefPubMedPubMedCentral

55.

Gevers D, Kugathasan S, Denson LA, Vázquez-Baeza Y, van Treuren W, Ren B, et al. The treatment-naive microbiome in new-onset Crohn’s disease. Cell Host Microbe. 2014;15:382–92. https://doi.org/10.1016/j.chom.2014.02.005.CrossRef

56.

Podschun, R Ullmann, U. Klebsiella spp. as nosocomial pathogens: epidemiology, taxonomy, typing methods, and pathogenicity factors. 11, 589–603 (1998).

57.

Ayars GH, Altman LC, Fretwell MD. Effect of decreased salivation and pH on the adherence of Klebsiella species to human buccal epithelial cells. Infect Immun. 1982;38:179–82. https://doi.org/10.1128/IAI.38.1.179-182.1982.CrossRefPubMedPubMedCentral

58.

Fair RJ, Tor Y. Antibiotics and bacterial resistance in the 21st century. Perspect Medicin Chem. 2014:25–64. https://doi.org/10.4137/PMC.S14459.CrossRef

59.

Signat BC, Pierre R, Poulet Danielle D. Role of Fusobacterium nucleatum in periodontal health and disease. Microb Ecol Health Dis. 1994;7:201–5.

60.

Han YW. Fusobacterium nucleatum: a commensal-turned pathogen. Curr Opin Microbiol. 2015;23:141–7. https://doi.org/10.1016/j.mib.2014.11.013.CrossRefPubMed

61.

M., C, et al. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res. 2012;22:299–306. https://doi.org/10.1101/gr.126516.111.CrossRef

62.

Genco CA, Van Dyke T, Amar S. Animal models for porphyromonas gingivalis-mediated periodontal disease. Trends Microbiol. 1998;6:444–9. https://doi.org/10.1016/S0966-842X(98)01363-8.CrossRefPubMed

63.

Mashima I, Nakazawa F. Interaction between Streptococcus spp and Veillonella tobetsuensis in the early stages of oral biofilm formation. J Bacteriol. 2015;197:2104–11. https://doi.org/10.1128/JB.02512-14.CrossRefPubMedPubMedCentral

64.

Kolenbrander, P. The genus Veillonella The Prokaryotes 87, 1022–1040 (2006).

65.

Abbas AA, et al. Redondoviridae , a family of small , circular DNA viruses of the human oro-respiratory tract associated with periodontitis and critical illness. Cell Host Microbe. 2019;25:719–729.e4. https://doi.org/10.1016/j.chom.2019.04.001.CrossRefPubMedPubMedCentral

66.

Blaser M, The J. Past and future biology of the human microbiome in an age of extinctions. Cell. 2018;172:1173–7. https://doi.org/10.1016/j.cell.2018.02.040.CrossRefPubMed

67.

Imhann F, Bonder MJ, Vich Vila A, Fu J, Mujagic Z, Vork L, et al. Proton pump inhibitors affect the gut microbiome. Gut. 2016;65:740–8. https://doi.org/10.1136/gutjnl-2015-310376.CrossRefPubMed

68.

Luo H, Fan Q, Xiao S, Chen K. Changes in proton pump inhibitor prescribing trend over the past decade and pharmacists’ effect on prescribing practice at a tertiary hospital. BMC Health Serv Res. 2018;18:1–10.

69.

Shah R, Richardson P, Yu H, Kramer J, Hou JK. Gastric acid suppression is associated with an increased risk of adverse outcomes in inflammatory bowel disease. Digestion. 2017;95:188–93. https://doi.org/10.1159/000455008.CrossRefPubMed

70.

Langdon A, Crook N, Dantas G. The effects of antibiotics on the microbiome throughout development and alternative approaches for therapeutic modulation. Genome Med. 2016;8. https://doi.org/10.1186/s13073-016-0294-z.

71.

Schulfer AF, Battaglia T, Alvarez Y, Bijnens L, Ruiz VE, Ho M, et al. Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice. Nat Microbiol. 2017;3:234–42. https://doi.org/10.1038/s41564-017-0075-5.CrossRefPubMedPubMedCentral

72.

Del Pozo JL, Patel R. The challenge of treating biofilm-associated bacterial infections. Clin Pharmacol Ther. 2007;82:204–9. https://doi.org/10.1038/sj.clpt.6100247.CrossRefPubMed

73.

Yee JKC. Helicobacter pylori colonization of the oral cavity: a milestone discovery. World J Gastroenterol. 2016;22:641–8. https://doi.org/10.3748/wjg.v22.i2.641.CrossRefPubMedPubMedCentral

74.

Hall CW, Mah TF. Molecular mechanisms of biofilm-based antibiotic resistance and tolerance in pathogenic bacteria. FEMS Microbiol Rev. 2017;41:276–301. https://doi.org/10.1093/femsre/fux010.CrossRefPubMed

75.

Brune F, Falk W, Fimmers R, S, Jepsen KJ. O042: Antibiotic resistance trends in human periodontitis microbiota (2008–2015). J Clin Periodontol. 2018;45:20.

76.

Card T, Logan RFA, Rodrigues LC, Wheeler JG. Antibiotic use and the development of Crohn’s disease. Gut. 2004;53:246–50. https://doi.org/10.1136/gut.2003.025239.CrossRefPubMedPubMedCentral

77.

Xun Z, Zhang Q, Xu T, Chen N, Chen F. Dysbiosis and ecotypes of the salivary microbiome associated with inflammatory bowel diseases and the assistance in diagnosis of diseases using oral bacterial profiles. Front Microbiol. 2018;9:1–17.CrossRef

Title: The Periodontal Microenvironment: a Potential Reservoir for Intestinal Pathobionts in Crohn’s Disease
Authors: Jiho Sohn
Yijun Sun
Robert J. Genco
Keith L. Kirkwood
Publication date: 01-03-2020
Publisher: Springer International Publishing
Keywords: Crohn's Disease
Chronic Inflammatory Bowel Disease
Oral Microbiota
Gingival Diseases
Respiratory Microbiota
Published in: Current Oral Health Reports / Issue 1/2020
Electronic ISSN: 2196-3002
DOI: https://doi.org/10.1007/s40496-020-00251-9

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

The Periodontal Microenvironment: a Potential Reservoir for Intestinal Pathobionts in Crohn’s Disease

Abstract

Purpose of Review

Recent Findings

Summary

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose of Review

Recent Findings

Summary

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