The "Gum-Gut" Axis in Inflammatory Bowel Diseases: A Hypothesis-Driven Review of Associations and Advances

Kevin M Byrd, Ajay S Gulati, Kevin M Byrd, Ajay S Gulati

Abstract

In modern medicine, the oral cavity has often been viewed as a passive conduit to the upper airways and gastrointestinal tract; however, its connection to the rest of the body has been increasingly explored over the last 40 years. For several diseases, the periodontium and gingiva are at the center of this oral-systemic link. Over 50 systemic conditions have been specifically associated with gingival and periodontal inflammation, including inflammatory bowel diseases (IBD), which have recently been elevated from simple "associations" to elegant, mechanistic investigations. IBD and periodontitis have been reported to impact each other's progression via a bidirectional relationship whereby chronic oral or intestinal inflammation can impact the other; however, the precise mechanisms for how this occurs remain unclear. Classically, the etiology of gingival inflammation (gingivitis) is oral microbial dysbiosis in the subgingival crevice that can lead to destructive periodontal disease (periodontitis); however, the current understanding of gingival involvement in IBD is that it may represent a separate disease entity from classical gingivitis, arising from mechanisms related to systemic inflammatory activation of niche-resident immune cells. Synthesizing available evidence, we hypothesize that once established, IBD can be driven by microbiomial and inflammatory changes originating specifically from the gingival niche through saliva, thereby worsening IBD outcomes and thus perpetuating a vicious cycle. In this review, we introduce the concept of the "gum-gut axis" as a framework for examining this reciprocal relationship between the periodontium and the gastrointestinal tract. To support and explore this gum-gut axis, we 1) provide a narrative review of historical studies reporting gingival and periodontal manifestations in IBD, 2) describe the current understanding and advances for the gum-gut axis, and 3) underscore the importance of collaborative treatment and research plans between oral and GI practitioners to benefit this patient population.

Keywords: Crohn’s disease; gingivitis; gum–gut; inflammatory bowel disease; microbiome; oral–gut; periodontitis; ulcerative colitis.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Byrd and Gulati.

Figures

Figure 1
Figure 1
A Bidirectional Influence of oral and systemic health. (A) Emerging associations between systemic disease on oral health include diseases of the skin, lungs, gastrointestinal tract as well as endocrine and hematopoietic systems. (B) The number of systemic diseases impacted by oral inflammatory diseases of the periodontium (gingivitis and periodontitis) continues to increase as more studies are conducted. Many of the same systems that influence oral health are influenced by periodontal health.
Figure 2
Figure 2
Evidence for IBD-induced gingivitis as a separate disease entity. (Left) “Classically” defined gingivitis involves well-defined increases to pro-inflammatory cytokines secondary to defined shifts in the microbiome. The inflammation clinically documented in IBD often discordant with biofilm deposits on the tooth surface, suggesting a role for the systemic inflammation of IBD to cause oral inflammation in parallel with or independent of biofilm deposits. This inflammation may itself shift the oral microbiome which then may cause further gingival inflammation. A sampling of the gingival crevicular fluid (GCF) and saliva (biofluids), gingival tissues (full-thickness biopsies), and subgingival microbes (microbiome) allows for a detailed understanding of the inflammatory and microbiomial shifts shared and unique to these possibly unique diseases.
Figure 3
Figure 3
The History of the gum–gut axis in IBD. Over many centuries, the chronic inflammatory diseases of the gut and periodontium were noted but not classified into defined disease entities until the late 1800s and early 1900s. First with case reports, then association studies, and finally clinical trials using biosampling primarily of the oral cavity, the evidence for the bidirectional relationship became better understood. More studies are required, including longitudinal cohorts, to understand the temporal associations and to further test causality.
Figure 4
Figure 4
Linking the gum–gut axis from birth to adulthood. Due to the uniqueness of each site, neonatal and adult oral and gut microbiomes do not resemble one another. However, a common feature is that both sites and their distinct niches are established with a nascent microbiome that diversifies during development. The oral microbiome stabilize at a later development timeframe when compared to the gut microbiome due to the shedding of primary teeth until about 12 years old and the subsequent eruption of permanent teeth. This provides a narrower window of gut microbiome vulnerability compared to the oral cavity. Both oral and gut microbiome diversification and stabilization are reportedly driven by environmental influences. The influence of the oral cavity to the lower gastrointestinal tract can occur via saliva and also via vasculature (local inflammation seeding to distant sites) whereas the primary mode of gut to oral influence is via the mechanisms of local-to-systemic inflammation such as the delivery of effector cytokines or activation of oral tissue-resident immune cells.
Figure 5
Figure 5
Future directions to better elucidate the gum–gut axis. Due to the uniquely active and remittent inflammatory states of periodontal disease and inflammatory bowel disease, there is an exciting future for collaborative efforts between GI and oral health care providers to answer these questions. This will require biosampling both oral and intestinal sites to correlate dysbiosis and inflammatory changes across niches and across time, better modeling using ex vivo models, and better phenotyping of both diseases. In the future, predictive modeling and precision medical approaches are possible to treat both oral and GI diseases.

References

    1. Braga AM, Squier CA. Ultrastructure of regenerating junctional epithelium in the monkey. J Periodontol (1980) 51(7):386–92. 10.1902/jop.1980.51.7.386
    1. Chen J, Jacox LA, Saldanha F, Sive H. Mouth development. Wiley Interdiscip Rev: Dev Biol (2017) 6(5):e275. 10.1002/wdev.275
    1. Nanci A, Ten CAR. Ten Cate's Oral Histology: Development, Structure, and Function. St. Louis, Mo: Mosby; (2017).
    1. Byrd KM, Piehl NC, Patel JH, Huh WJ, Sequeira I, Lough KJ, et al. . Heterogeneity within Stratified Epithelial Stem Cell Populations Maintains the Oral Mucosa in Response to Physiological Stress. Cell Stem Cell (2019) 25(6):814–29.e816. 10.1016/j.stem.2019.11.005
    1. Regezi JA, Sciubba JJ, Jordan RC. Oral pathology: clinical pathologic correlations. 6th Ed, St. Louis: Elsevier Saunders; (2016) 388.
    1. Askitopoulou H, Nyktari V, Papaioannou A, Stefanakis G, Konsolaki E. The Origins of Oral Medicine in the Hippocratic Collected Works. J Oral Pathol Med (2017) 46(9):689–94. 10.1111/jop.12615
    1. Löe H. Periodontal diseases: a brief historical perspective. Periodontol 2000 (1993) 2(1):7–12. 10.1111/j.1600-0757.1993.tb00215.x
    1. Baron JH. Inflammatory bowel disease up to 1932. Mt Sinai J Med (2000) 67(3):174–89.
    1. Donoff B, McDonough JE, Riedy CA. Integrating oral and general health care. N Engl J Med (2014) 371(24):2247–9. 10.1056/NEJMp1410824
    1. Rabiei S, Mohebbi SZ, Patja K, Virtanen JI. Physicians’ knowledge of and adherence to improving oral health. BMC Public Health (2012) 12(1):1–9. 10.1186/1471-2458-12-855
    1. Elad S, Zadik Y, Caton JG, Epstein JB. Oral mucosal changes associated with primary diseases in other body systems. Periodontol 2000 (2019) 80(1):28–48. 10.1111/prd.12265
    1. Squier CA, Kremer MJ. Biology of oral mucosa and esophagus. JNCI Monogr (2001) 2001(29):7–15. 10.1093/oxfordjournals.jncimonographs.a003443
    1. Muhvić-Urek M, Tomac-Stojmenović M, Mijandrušić-Sinčić B. Oral pathology in inflammatory bowel disease. World J Gastroenterol (2016) 22(25):5655. 10.3748/wjg.v22.i25.5655
    1. Barnett ML. The oral-systemic disease connection: An update for the practicing dentist. J Am Dental Assoc (2006) 137:S5–6. 10.14219/jada.archive.2006.0401
    1. Genco RJ, Borgnakke WS. Risk factors for periodontal disease. Periodontol 2000 (2013) 62(1):59–94. 10.1111/j.1600-0757.2012.00457.x
    1. Cianciola L, Park B, Bruck E, Mosovich L, Genco R. Prevalence of periodontal disease in insulin-dependent diabetes mellitus (juvenile diabetes). J Am Dental Assoc (1982) 104(5):653–60. 10.14219/jada.archive.1982.0240
    1. Beck J, Garcia R, Heiss G, Vokonas PS, Offenbacher S. Periodontal disease and cardiovascular disease. J Periodontol (1996) 67(10s):1123–37. 10.1902/jop.1996.67.10s.1123
    1. Offenbacher S, Katz V, Fertik G, Collins J, Boyd D, Maynor G, et al. . Periodontal infection as a possible risk factor for preterm low birth weight. J Periodontol (1996) 67(10s):1103–13. 10.1902/jop.1996.67.10s.1103
    1. Cullinan MP, Seymour GJ. Periodontal disease and systemic illness: will the evidence ever be enough? Periodontol 2000 (2013) 62(1):271–86. 10.1111/prd.12007
    1. Pihlstrom BL, Hodges JS, Michalowicz B, Wohlfahrt JC, Garcia RI. Promoting oral health care because of its possible effect on systemic disease is premature and may be misleading. J Am Dent Assoc (2018) 149(6):401–3. 10.1016/j.adaj.2018.03.030
    1. Monsarrat P, Blaizot A, Kémoun P, Ravaud P, Nabet C, Sixou M, et al. . Clinical research activity in periodontal medicine: a systematic mapping of trial registers. J Clin Periodontol (2016) 43(5):390–400. 10.1111/jcpe.12534
    1. Herrera D, Molina A, Buhlin K, Klinge B. Periodontal diseases and association with atherosclerotic disease. Periodontol 2000 (2020) 83(1):66–89. 10.1111/prd.12302
    1. Bobetsis YA, Graziani F, Gürsoy M, Madianos PN. Periodontal disease and adverse pregnancy outcomes. Periodontol 2000 (2020) 83(1):154–74. 10.1111/prd.12294
    1. Borgnakke WS, Ylöstalo PV, Taylor GW, Genco RJ. Effect of periodontal disease on diabetes: systematic review of epidemiologic observational evidence. J Periodontol (2013) 84:S135–52. 10.1111/jcpe.12080
    1. Rapone B, Corsalini M, Converti I, Loverro MT, Gnoni A, Trerotoli P, et al. . Does Periodontal Inflammation Affect Type 1 Diabetes in Childhood and Adolescence? A Meta-Analysis. Front Endocrinol (2020) 11:278. 10.3389/fendo.2020.00278
    1. Jepsen S, Suvan J, Deschner J. The association of periodontal diseases with metabolic syndrome and obesity. Periodontol 2000 (2020) 83(1):125–53. 10.1111/prd.12326
    1. Lira-Junior R, Figueredo CM. Periodontal and inflammatory bowel diseases: Is there evidence of complex pathogenic interactions? World J Gastroenterol (2016) 22(35):7963. 10.3748/wjg.v22.i35.7963
    1. Atarashi K, Suda W, Luo C, Kawaguchi T, Motoo I, Narushima S, et al. . Ectopic colonization of oral bacteria in the intestine drives TH1 cell induction and inflammation. Science (2017) 358(6361):359–65. 10.1126/science.aan4526
    1. Kitamoto S, Nagao-Kitamoto H, Jiao Y, Gillilland III MG, Hayashi A, Imai J, et al. . The Intermucosal Connection between the Mouth and Gut in Commensal Pathobiont-Driven Colitis. Cell (2020) 182(2):447–62.e14. 10.1016/j.cell.2020.05.048
    1. Eke PI, Thornton-Evans GO, Wei L, Borgnakke WS, Dye BA, Genco RJ. Periodontitis in US adults: National health and nutrition examination survey 2009-2014. J Am Dental Assoc (2018) 149(7):576–88.e576. 10.1016/j.adaj.2018.04.023
    1. Kassebaum NJ, Bernabe E, Dahiya M, Bhandari B, Murray CJ, Marcenes W. Global burden of severe periodontitis in 1990-2010: a systematic review and meta-regression. J Dental Res (2014) 93(11):1045–53. 10.1177/0022034514552491
    1. Caton JG, Armitage G, Berglundh T, Chapple IL, Jepsen S, Kornman KS, et al. . A new classification scheme for periodontal and peri-implant diseases and conditions–Introduction and key changes from the 1999 classification. J Periodontol (2018) 89:S1–8. 10.1002/JPER.18-0157
    1. Chapple IL, Mealey BL, Van Dyke TE, Bartold PM, Dommisch H, Eickholz P, et al. . Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol (2018) 89:S74–84. 10.1002/JPER.17-0719
    1. Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, et al. . Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol (2018) 89:S173–82. 10.1002/JPER.17-0721
    1. Berezow AB, Darveau RP. Microbial shift and periodontitis. Periodontol 2000 (2011) 55(1):36–47. 10.1111/j.1600-0757.2010.00350.x
    1. Abusleme L, Dupuy AK, Dutzan N, Silva N, Burleson JA, Strausbaugh LD, et al. . The subgingival microbiome in health and periodontitis and its relationship with community biomass and inflammation. ISME J (2013) 7(5):1016–25. 10.1038/ismej.2012.174
    1. Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Primers (2017) 3:17038. 10.1038/nrdp.2017.38
    1. Eke PI, Borgnakke WS, Genco RJ. Recent epidemiologic trends in periodontitis in the USA. Periodontol 2000 (2020) 82(1):257–67. 10.1111/prd.12323
    1. Lauritano D, Boccalari E, Di Stasio D, Della Vella F, Carinci F, Lucchese A, et al. . Prevalence of oral lesions and correlation with intestinal symptoms of inflammatory bowel disease: a systematic review. Diagnostics (2019) 9(3):77. 10.3390/diagnostics9030077
    1. GBD 2017 Inflammatory Bowel Disease Collaborators . The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol (2020) 5(1):17–30. 10.1016/S2468-1253(19)30333-4
    1. Haller CA, Markowitz J. IBD in children: lessons for adults. Curr Gastroenterol Rep (2007) 9(6):528–32. 10.1007/s11894-007-0070-8
    1. Kim HJ, Oh SH, Kim DY, Lee HS, Park SH, Yang SK, et al. . Clinical Characteristics and Long-Term Outcomes of Paediatric Crohn’s Disease: A Single-Centre Experience. J Crohns Colitis (2017) 11(2):157–64. 10.1093/ecco-jcc/jjw146
    1. Turpin W, Goethel A, Bedrani L, Croitoru MK. Determinants of IBD heritability: genes, bugs, and more. Inflamm Bowel Dis (2018) 24(6):1133–48. 10.1093/ibd/izy085
    1. Nibali L, Bayliss-Chapman J, Almofareh S, Zhou Y, Divaris K, Vieira A. What is the heritability of periodontitis? A systematic review. J Dental Res (2019) 98(6):632–41. 10.1177/0022034519842510
    1. Brandtzaeg P. Inflammatory bowel disease: clinics and pathology. Do inflammatory bowel disease and periodontal disease have similar immunopathogeneses? Acta Odontol Scand (2001) 59(4):235–43. 10.1080/00016350152509265
    1. Indriolo A, Greco S, Ravelli P, Fagiuoli S. What can we learn about biofilm/host interactions from the study of inflammatory bowel disease. J Clin Periodontol (2011) 38:36–43. 10.1111/j.1600-051X.2010.01680.x
    1. Zippi M, Corrado C, Pica R, Avallone EV, Cassieri C, De Nitto D, et al. . Extraintestinal manifestations in a large series of Italian inflammatory bowel disease patients. World J Gastroenterol (2014) 20(46):17463. 10.3748/wjg.v20.i46.17463
    1. Greuter T, Bertoldo F, Rechner R, Straumann A, Biedermann L, Zeitz J, et al. . Extraintestinal manifestations of pediatric inflammatory bowel disease: prevalence, presentation, and anti-TNF treatment. J Pediatr Gastroenterol Nutr (2017) 65(2):200–6. 10.1097/MPG.0000000000001455
    1. Pittock S, Drumm B, Fleming P, McDermott M, Imrie C, Flint S, et al. . The oral cavity in Crohn’s disease. J Pediatr (2001) 138(5):767–71. 10.1067/mpd.2001.113008
    1. Katz J, Shenkman A, Stavropoulos F, Melzer E. Oral signs and symptoms in relation to disease activity and site of involvement in patients with inflammatory bowel disease. Oral Dis (2003) 9(1):34–40. 10.1034/j.1601-0825.2003.00879.x
    1. Zbar AP, Ben-Horin S, Beer-Gabel M, Eliakim R. Oral Crohn’s disease: Is it a separable disease from orofacial granulomatosis? A review. J Crohn’s Colitis (2012) 6(2):135–42. 10.1016/j.crohns.2011.07.001
    1. Skrzat A, Olczak-Kowalczyk D, Turska-Szybka A. Crohn’s disease should be considered in children with inflammatory oral lesions. Acta Paediatr (2017) 106(2):199–203. 10.1111/apa.13686
    1. Jose FA, Garnett EA, Vittinghoff E, Ferry GD, Winter HS, Baldassano RN, et al. . Development of extraintestinal manifestations in pediatric patients with inflammatory bowel disease. Inflamm Bowel Dis (2009) 15(1):63–8. 10.1002/ibd.20604
    1. Chandan J, Thomas T. The impact of inflammatory bowel disease on oral health. Br Dental J (2017) 222(7):549–53. 10.1038/sj.bdj.2017.318
    1. Katsanos K, Torres J, Roda G, Brygo A, Delaporte E, Colombel JF. Non-malignant oral manifestations in inflammatory bowel diseases. Alimentary Pharmacol Ther (2015) 42(1):40–60. 10.1111/apt.13217
    1. Ojha J, Cohen DM, Islam NM, Stewart CM, Katz J, Bhattacharyya I. Gingival involvement in Crohn disease. J Am Dental Assoc (2007) 138(12):1574–81. 10.14219/jada.archive.2007.0106
    1. Plauth M, Jenss H, Meyle J. Oral manifestations of Crohn’s disease. An analysis of 79 cases. J Clin Gastroenterol (1991) 13(1):29–37. 10.1097/00004836-199102000-00008
    1. Eckel A, Lee D, Deutsch G, Maxin A, Oda D. Oral manifestations as the first presenting sign of Crohn’s disease in a pediatric patient. J Clin Exp Dent (2017) 9(7):e934. 10.4317/jced.53914
    1. Lang NP, Lindhe J. eds. Clinical Periodontology and Implant Dentistry. New York, NY, USA: John Wiley & Sons; (2015).
    1. Lang NP, Bartold PM. Periodontal health. J Periodontol (2018) 89:S9–S16. 10.1002/JPER.16-0517
    1. Löe H, Theilade E, Jensen SB. Experimental Gingivitis in Man. J Periodontol (1965) 36:177–87. 10.1902/jop.1965.36.3.177
    1. Page RC, Schroeder HE. Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Invest (1976) 34(3):235–49.
    1. Trombelli L, Farina R, Silva CO, Tatakis DN. Plaque-induced gingivitis: Case definition and diagnostic considerations. J Clin Periodontol (2018) 45:S44–67. 10.1111/jcpe.12939
    1. Hugoson A, Koch G, Rylander H. Prevalence and distribution of gingivitis-periodontitis in children and adolescents. Epidemiological data as a base for risk group selection. Swed Dent J (1981) 5(3):91–103.
    1. Lindhe J, Rylander H. Experimental gingivitis in young dogs. Eur J Oral Sci (1975) 83(6):314–26. 10.1111/j.1600-0722.1975.tb00444.x
    1. Zemouri C, Jakubovics NS, Crielaard W, Zaura E, Dodds M, Schelkle B, et al. . Resistance and resilience to experimental gingivitis: a systematic scoping review. BMC Oral Health (2019) 19(1):212. 10.1186/s12903-019-0889-z
    1. Schincaglia G, Hong B, Rosania A, Barasz J, Thompson A, Sobue T, et al. . Clinical, immune, and microbiome traits of gingivitis and peri-implant mucositis. J Dental Res (2017) 96(1):47–55. 10.1177/0022034516668847
    1. Mira A, Simon-Soro A, Curtis M. Role of microbial communities in the pathogenesis of periodontal diseases and caries. J Clin Periodontol (2017) 44:S23–38. 10.1111/jcpe.12671
    1. Lim ML, Wallace MR. Infectious diarrhea in history. Infect Dis Clinics North Am (2004) 18(2):261. 10.1016/j.idc.2004.01.006
    1. Mulder DJ, Noble AJ, Justinich CJ, Duffin JM. A tale of two diseases: the history of inflammatory bowel disease. J Crohn’s Colitis (2014) 8(5):341–8. 10.1016/j.crohns.2013.09.009
    1. Merritt AH. A brief history of periodontology. J Dental Res (1921) 3(4):cxlix–clxi. 10.1177/00220345210030040707
    1. Sircus W, Church R, Kelleher J. Recurrent aphthous ulceration of the mouth; a study of the natural history, aetiology, and treatment. Q J Med (1957) 26(102):235–49.
    1. Dudeney TP. Crohn’s disease of the mouth. Proc R Soc Med (1969) 62(12):1237. 10.1177/003591576906201218
    1. Croft CB, Wilkinson AR. Ulceration of the mouth, pharynx, and larynx in Crohn’s disease of the intestine. Br J Surg (1972) 59(4):249–52. 10.1002/bjs.1800590402
    1. Stankler L, Ewen SW, Kerr NW. Crohn’s disease of the mouth. Br J Dermatol (1972) 87(5):501–4. 10.1111/j.1365-2133.1972.tb01599.x
    1. Asquith P, Thompson RA, Cooke WT. Oral manifestations of Crohn’s disease. Gut (1975) 16(4):249–54. 10.1136/gut.16.4.249
    1. Snyder M, Cawson R. Oral changes in Crohn’s disease. J Oral Surg (1976) 34(7):594–9.
    1. Schiller KF, Golding PL, Peebles RA, Whitehead R. Crohn’s disease of the mouth and lips. Gut (1971) 12(10):864–5.
    1. Ellis JP. Crohn’s disease with mouth involvement. Proc R Soc Med (1972) 65(12):1080. 10.1177/003591577206501211
    1. Bottomley WK, Giorgini GL, Julienne CH. Oral extension of regional enteritis (Crohn’s disease). Report of a case. Oral Surg Oral Med Oral Pathol (1972) 34(3):417–20. 10.1016/0030-4220(72)90317-9
    1. Bernstein ML, McDonald JS. Oral lesions in Crohn’s disease: report of two cases and update of the literature. Oral Surg Oral Med Oral Pathol (1978) 46(2):234–45. 10.1016/0030-4220(78)90198-6
    1. Sachar D, Auslander M. Missing pieces in the puzzle of Crohn’s disease. Gastroenterology (1978) 75(4):745. 10.1016/S0016-5085(19)31718-4
    1. Lamster IB, Rodrick ML, Sonis ST, Falchuk ZM. An analysis of peripheral blood and salivary polymorphonuclear leukocyte function, circulating immune complex levels and oral status in patients with inflammatory bowel disease. J Periodontol (1982) 53(4):231–8. 10.1902/jop.1982.53.4.231
    1. Engel LD, Pasquinelli KL, Leone SA, Moncla BJ, Nielson KD, Rabinovitch PS. Abnormal lymphocyte profiles and leukotriene B4 status in a patient with Crohn’s disease and severe periodontitis. J Periodontol (1988) 59(12):841–7. 10.1902/jop.1988.59.12.841
    1. 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(8):1839–46. 10.1097/MIB.0000000000000452
    1. Flemmig TF, Shanahan F, Miyasaki KT. Prevalence and severity of periodontal disease in patients with inflammatory bowel disease. J Clin Periodontol (1991) 18(9):690–7. 10.1111/j.1600-051X.1991.tb00111.x
    1. Grössner-Schreiber B, Fetter T, Hedderich J, Kocher T, Schreiber S, Jepsen S. Prevalence of dental caries and periodontal disease in patients with inflammatory bowel disease: a case–control study. J Clin Periodontol (2006) 33(7):478–84. 10.1111/j.1600-051X.2006.00942.x
    1. Brito F, Barros FCD, Zaltman C, Pugas Carvalho AT, de Vasconcellos 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(6):555–60. 10.1111/j.1600-051X.2008.01231.x
    1. Habashneh R, Khader Y, Alhumouz M, Jadallah K, Ajlouni Y. The association between inflammatory bowel disease and periodontitis among Jordanians: a case–control study. J Periodontal Res (2012) 47(3):293–8. 10.1111/j.1600-0765.2011.01431.x
    1. 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(13):2768–77. 10.1097/01.MIB.0000438356.84263.3b
    1. She Y-y, Kong X-B, Ge Y-P, Liu Z-Y, Chen J-Y, Jiang J-W, et al. . Periodontitis and inflammatory bowel disease: a meta-analysis. BMC Oral Health (2020) 20(1):1–11. 10.1186/s12903-020-1053-5
    1. Papageorgiou SN, Hagner M, Nogueira AV, Franke A, Jager A, Deschner J. Inflammatory bowel disease and oral health: systematic review and a meta-analysis. J Clin Periodontol (2017) 44(4):382–93. 10.1111/jcpe.12698
    1. Ten Cate AR. The role of epithelium in the development, structure and function of the tissues of tooth support. Oral Dis (1996) 2(1):55–62. 10.1111/j.1601-0825.1996.tb00204.x
    1. Bosshardt DD, Lang NP. The junctional epithelium: from health to disease. J Dental Res (2005) 84(1):9–20. 10.1177/154405910508400102
    1. Dutzan N, Abusleme L, Bridgeman H, Greenwell-Wild T, Zangerle-Murray T, Fife ME, et al. . On-going Mechanical Damage from Mastication Drives Homeostatic Th17 Cell Responses at the Oral Barrier. Immunity (2017) 46(1):133–47. 10.1016/j.immuni.2016.12.010
    1. Curtis MA, Diaz PI, Van Dyke TE. The role of the microbiota in periodontal disease. Periodontol 2000 (2020) 83(1):14–25. 10.1111/prd.12296
    1. Moskow BS, Poison AM. Histologic studies on the extension of the inflammatory infiltrate in human periodontitis. J Clin Periodontol (1991) 18(7):534–42. 10.1111/j.1600-051X.1991.tb00086.x
    1. Dutzan N, Konkel JE, Greenwell-Wild T, Moutsopoulos NM. Characterization of the human immune cell network at the gingival barrier. Mucosal Immunol (2016) 9(5):1163–72. 10.1038/mi.2015.136
    1. Presland RB, Dale BA. Epithelial structural proteins of the skin and oral cavity: function in health and disease. Crit Rev Oral Biol Med (2000) 11(4):383–408. 10.1177/10454411000110040101
    1. Dale BA. Periodontal epithelium: a newly recognized role in health and disease. Periodontol 2000 (2002) 30:70–8. 10.1034/j.1600-0757.2002.03007.x
    1. Fujita T, Yoshimoto T, Kajiya M, Ouhara K, Matsuda S, Takemura T, et al. . Regulation of defensive function on gingival epithelial cells can prevent periodontal disease. Jpn Dental Sci Rev (2018) 54(2):66–75. 10.1016/j.jdsr.2017.11.003
    1. Moutsopoulos NM, Konkel JE. Tissue-Specific Immunity at the Oral Mucosal Barrier. Trends Immunol (2018) 39(4):276–87. 10.1016/j.it.2017.08.005
    1. Huang N, Perez P, Kato T, Mikami Y, Okuda K, Gilmore RC, et al. . Integrated Single-Cell Atlases Reveal an Oral SARS-CoV-2 Infection and Transmission Axis. medRxiv [Preprint] (2020). 10.1101/2020.10.26.20219089. 2020.2010.2026.20219089.
    1. Caetano AJ, Yianni V, Volponi A, Booth V, D'Agostino EM, Sharpe P. Defining human mesenchymal and epithelial heterogeneity in response to oral inflammatory disease. Elife (2021) 10:e62810. 10.7554/eLife.62810
    1. Nishida M, Grossi SG, Dunford RG, Ho AW, Trevisan M, Genco RJ. Dietary vitamin C and the risk for periodontal disease. J Periodontol (2000) 71(8):1215–23. 10.1902/jop.2000.71.8.1215
    1. Hou JK, Abraham B, El-Serag H. Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature. Am J Gastroenterol (2011) 106(4):563–73. 10.1038/ajg.2011.44
    1. Yan H, Wang H, Zhang X, Li X, Yu J. Ascorbic acid ameliorates oxidative stress and inflammation in dextran sulfate sodium-induced ulcerative colitis in mice. Int J Clin Exp Med (2015) 8(11):20245–53.
    1. Najeeb S, Zafar MS, Khurshid Z, Zohaib S, Almas K. The role of nutrition in periodontal health: an update. Nutrients (2016) 8(9):530. 10.3390/nu8090530
    1. Lamster I, Sonis S, Hannigan A, Kolodkin A. An association between Crohn’s disease, periodontal disease and enhanced neutrophil function. J Periodontol (1978) 49(9):475–9. 10.1902/jop.1978.49.9.475
    1. Said HS, Suda W, Nakagome S, Chinen H, Oshima K, Kim S, et al. . Dysbiosis of salivary microbiota in inflammatory bowel disease and its association with oral immunological biomarkers. DNA Res (2013) 21(1):15–25. 10.1093/dnares/dst037
    1. Szczeklik K, Owczarek D, Pytko-Polończyk J, Kęsek B, Mach TH. Proinflammatory cytokines in the saliva of patients with active and nonactive Crohn’s. Pol Arch Med Wewn (2012) 122(5):200–8. 10.20452/pamw.1256
    1. Figueredo CM, Martins AP, Lira-Junior R, Menegat JB, Carvalho AT, Fischer RG, et al. . Activity of inflammatory bowel disease influences the expression of cytokines in gingival tissue. Cytokine (2017) 95:1–6. 10.1016/j.cyto.2017.01.016
    1. Damen GM, Hol J, de Ruiter L, Bouquet J, Sinaasappel M, van der Woude J, et al. . Chemokine production by buccal epithelium as a distinctive feature of pediatric Crohn disease. J Pediatr Gastroenterol Nutr (2006) 42(2):142–9. 10.1097/01.mpg.0000189336.70021.8a
    1. Menegat JSB, Lira-Junior R, Siqueira MA, Brito F, Carvalho AT, Fischer RG, et al. . Cytokine expression in gingival and intestinal tissues of patients with periodontitis and inflammatory bowel disease: An exploratory study. Arch Oral Biol (2016) 66:141–6. 10.1016/j.archoralbio.2016.02.018
    1. Van Dyke T, Dowell V, Offenbacher S, Snyder W, Hersh T. Potential role of microorganisms isolated from periodontal lesions in the pathogenesis of inflammatory bowel disease. Infect Immun (1986) 53(3):671–7. 10.1128/IAI.53.3.671-677.1986
    1. Kaakoush NO, Mitchell HM. Campylobacter concisus–a new player in intestinal disease. Front Cell Infect Microbiol (2012) 2:4. 10.3389/fcimb.2012.00004
    1. Liu F, Ma R, Wang Y, Zhang L. The clinical importance of Campylobacter concisus and other human hosted Campylobacter species. Front Cell Infect Microbiol (2018) 8:243. 10.3389/fcimb.2018.00243
    1. Graves D, Corrêa J, Silva T. The oral microbiota is modified by systemic diseases. J Dental Res (2019) 98(2):148–56. 10.1177/0022034518805739
    1. Rautava J, Pinnell LJ, Vong L, Akseer N, Assa A, Sherman PM. Oral microbiome composition changes in mouse models of colitis. J Gastroenterol Hepatol (2015) 30(3):521–7. 10.1111/jgh.12713
    1. Brakenhoff LK, van der Heijde DM, Hommes DW, Huizinga TW, Fidder HH. The joint—gut axis in inflammatory bowel diseases. J Crohn’s Colitis (2010) 4(3):257–68. 10.1016/j.crohns.2009.11.005
    1. Vavricka SR, Schoepfer A, Scharl M, Lakatos PL, Navarini A, Rogler G. Extraintestinal manifestations of inflammatory bowel disease. Inflamm Bowel Dis (2015) 21(8):1982–92. 10.1097/MIB.0000000000000392
    1. Docktor MJ, Paster BJ, Abramowicz S, Ingram J, Wang YE, Correll M, et al. . Alterations in diversity of the oral microbiome in pediatric inflammatory bowel disease. Inflamm Bowel Dis (2012) 18(5):935–42. 10.1002/ibd.21874
    1. Kelsen J, Bittinger K, Pauly-Hubbard H, Posivak L, Grunberg S, Baldassano R, et al. . Alterations of the subgingival microbiota in pediatric Crohn’s disease studied longitudinally in discovery and validation cohorts. Inflamm Bowel Dis (2015) 21(12):2797–805. 10.1097/MIB.0000000000000557
    1. Brito F, Zaltman C, Carvalho AT, Fischer RG, Persson R, Gustafsson A, et al. . Subgingival microflora in inflammatory bowel disease patients with untreated periodontitis. Eur J Gastroenterol Hepatol (2013) 25(2):239–45. 10.1097/MEG.0b013e32835a2b70
    1. 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) 9:1136. 10.3389/fmicb.2018.01136
    1. Fourie NH, Wang D, Abey SK, Sherwin LB, Joseph PV, Rahim-Williams B, et al. . The microbiome of the oral mucosa in irritable bowel syndrome. Gut Microbes (2016) 7(4):286–301. 10.1080/19490976.2016.1162363
    1. Gensollen T, Iyer SS, Kasper DL, Blumberg RS. How colonization by microbiota in early life shapes the immune system. Science (2016) 352(6285):539–44. 10.1126/science.aad9378
    1. Ramanan D, Sefik E, Galván-Peña S, Wu M, Yang L, Yang Z, et al. . An immunologic mode of multigenerational transmission governs a gut Treg setpoint. Cell (2020) 181(6):1276–90.e13. 10.1016/j.cell.2020.04.030
    1. Dewhirst FE, Chen T, Izard J, Paster BJ, Tanner AC, Yu W-H, et al. . The human oral microbiome. J Bacteriol (2010) 192(19):5002–17. 10.1128/JB.00542-10
    1. Xiao J, Fiscella KA, Gill SR. Oral microbiome: possible harbinger for children’s health. Int J Oral Sci (2020) 12(1):1–13. 10.1038/s41368-020-0082-x
    1. Dominguez-Bello MG, Godoy-Vitorino F, Knight R, Blaser MJ. Role of the microbiome in human development. Gut (2019) 68(6):1108–14. 10.1136/gutjnl-2018-317503
    1. Gest H. The discovery of microorganisms by Robert Hooke and Antoni Van Leeuwenhoek, fellows of the Royal Society. Notes Rec R Soc London (2004) 58(2):187–201. 10.1098/rsnr.2004.0055
    1. Escapa I, Chen T, Huang Y, Gajare P, Dewhirst F, Lemon K. New Insights into Human Nostril Microbiome from the Expanded Human Oral Microbiome Database (eHOMD): a Resource for the Microbiome of the Human Aerodigestive Tract. mSystems (2018) 3(6):e00187–18. 10.1128/mSystems.00187-18
    1. Gao L, Xu T, Huang G, Jiang S, Gu Y, Chen F. Oral microbiomes: more and more importance in oral cavity and whole body. Protein Cell (2018) 9(5):488–500. 10.1007/s13238-018-0548-1
    1. Aleti G, Baker JL, Tang X, Alvarez R, Dinis M, Tran NC, et al. . Identification of the bacterial biosynthetic gene clusters of the oral microbiome illuminates the unexplored social language of bacteria during health and disease. MBio (2019) 10(2):e00321–19. 10.1128/mBio.00321-19
    1. Balachandran M, Cross KL, Podar M. Single-cell genomics and the oral microbiome. J Dental Res (2020) 99(6):613–20. 10.1177/0022034520907380
    1. Lamont RJ, Koo H, Hajishengallis G. The oral microbiota: dynamic communities and host interactions. Nat Rev Microbiol (2018) 16(12):745–59. 10.1038/s41579-018-0089-x
    1. Segata N, Haake SK, Mannon P, Lemon KP, Waldron L, Gevers D, et al. . Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples. Genome Biol (2012) 13(6):R42. 10.1186/gb-2012-13-6-r42
    1. Maki KA, Kazmi N, Barb JJ, Ames N. The Oral and Gut Bacterial Microbiomes: Similarities, Differences, and Connections. Biol Res For Nurs (2021) 23(1):7–20 10.1177/1099800420941606
    1. Kilian M, Chapple I, Hannig M, Marsh P, Meuric V, Pedersen A, et al. . The oral microbiome–an update for oral healthcare professionals. Br Dental J (2016) 221(10):657. 10.1038/sj.bdj.2016.865
    1. Waggoner-Fountain LA, Whit Walker M, Hollis RJ, Pfaller MA, Ferguson JE, Wenzel RP, et al. . Vertical and horizontal transmission of unique Candida species to premature newborns. Clin Infect Dis (1996) 22(5):803–8. 10.1093/clinids/22.5.803
    1. Bliss JM, Basavegowda KP, Watson WJ, Sheikh AU, Ryan RM. Vertical and horizontal transmission of Candida albicans in very low birth weight infants using DNA fingerprinting techniques. Pediatr Infect Dis J (2008) 27(3):231–5. 10.1097/INF.0b013e31815bb69d
    1. Brito IL, Gurry T, Zhao S, Huang K, Young SK, Shea TP, et al. . Transmission of human-associated microbiota along family and social networks. Nat Microbiol (2019) 4(6):964–71. 10.1038/s41564-019-0409-6
    1. Payne M, Hashim A, Alsam A, Joseph S, Aduse-Opoku J, Wade W, et al. . Horizontal and Vertical Transfer of Oral Microbial Dysbiosis and Periodontal Disease. J Dental Res (2019) 98(13):1503–10. 10.1177/0022034519877150
    1. Xu X, He J, Xue J, Wang Y, Li K, Zhang K, et al. . Oral cavity contains distinct niches with dynamic microbial communities. Environ Microbiol (2015) 17(3):699–710. 10.1111/1462-2920.12502
    1. Gensollen T, Blumberg RS. Correlation between early-life regulation of the immune system by microbiota and allergy development. J Allergy Clin Immunol (2017) 139(4):1084–91. 10.1016/j.jaci.2017.02.011
    1. Constantinides MG, Link VM, Tamoutounour S, Wong AC, Perez-Chaparro PJ, Han S-J, et al. . MAIT cells are imprinted by the microbiota in early life and promote tissue repair. Science (2019) 366(6464):eaax6624. 10.1126/science.aax6624
    1. Al Nabhani Z, Eberl G. Imprinting of the immune system by the microbiota early in life. Mucosal Immunol (2020) 13(2):183–9. 10.1038/s41385-020-0257-y
    1. Perez-Muñoz ME, Arrieta M-C, Ramer-Tait AE, Walter J. A critical assessment of the “sterile womb” and “in utero colonization” hypotheses: implications for research on the pioneer infant microbiome. Microbiome (2017) 5(1):48. 10.1186/s40168-017-0268-4
    1. Stinson LF, Boyce MC, Payne MS, Keelan JA. The not-so-sterile womb: evidence that the human fetus is exposed to bacteria prior to birth. Front Microbiol (2019) 10:1124. 10.3389/fmicb.2019.01124
    1. Rackaityte E, Halkias J, Fukui E, Mendoza V, Hayzelden C, Crawford E, et al. . Viable bacterial colonization is highly limited in the human intestine in utero. Nat Med (2020) 26(4):599–607. 10.1038/s41591-020-0761-3
    1. Ding T, Schloss PD. Dynamics and associations of microbial community types across the human body. Nature (2014) 509(7500):357–60. 10.1038/nature13178
    1. Rodríguez JM, Murphy K, Stanton C, Ross RP, Kober OI, Juge N, et al. . The composition of the gut microbiota throughout life, with an emphasis on early life. Microbial Ecol Health Dis (2015) 26(1):26050. 10.3402/mehd.v26.26050
    1. Stras SF, Werner L, Toothaker JM, Olaloye OO, Oldham AL, McCourt CC, et al. . Maturation of the human intestinal immune system occurs early in fetal development. Dev Cell (2019) 51(3):357–73.e355. 10.1016/j.devcel.2019.09.008
    1. Ruiz L, Delgado S, Ruas-Madiedo P, Sánchez B, Margolles A. Bifidobacteria and their molecular communication with the immune system. Front Microbiol (2017) 8:2345. 10.3389/fmicb.2017.02345
    1. Derrien M, van Passel MW, van de Bovenkamp JH, Schipper R, de Vos W, Dekker J. Mucin-bacterial interactions in the human oral cavity and digestive tract. Gut Microbes (2010) 1(4):254–68. 10.4161/gmic.1.4.12778
    1. Toda K, Hisata K, Satoh T, Katsumata N, Odamaki T, Mitsuyama E, et al. . Neonatal oral fluid as a transmission route for bifidobacteria to the infant gut immediately after birth. Sci Rep (2019) 9(1):1–9. 10.1038/s41598-019-45198-9
    1. Weström B, Arévalo Sureda E, Pierzynowska K, Pierzynowski SG, Pérez-Cano F-J. The Immature Gut Barrier and Its Importance in Establishing Immunity in Newborn Mammals. Front Immunol (2020) 11:1153. 10.3389/fimmu.2020.01153
    1. Abeles SR, Robles-Sikisaka R, Ly M, Lum AG, Salzman J, Boehm TK, et al. . Human oral viruses are personal, persistent and gender-consistent. ISME J (2014) 8(9):1753–67. 10.1038/ismej.2014.31
    1. Wilbert SA, Welch JLM, Borisy GG. Spatial ecology of the human tongue dorsum microbiome. Cell Rep (2020) 30(12):4003–15.e4003. 10.1016/j.celrep.2020.02.097
    1. Mark Welch JL, Dewhirst FE, Borisy GG. Biogeography of the Oral microbiome: the site-specialist hypothesis. Annu Rev Microbiol (2019) 73:335–58. 10.1146/annurev-micro-090817-062503
    1. Proctor DM, Fukuyama JA, Loomer PM, Armitage GC, Lee SA, Davis NM, et al. . A spatial gradient of bacterial diversity in the human oral cavity shaped by salivary flow. Nat Commun (2018) 9(1):681. 10.1038/s41467-018-02900-1
    1. Proctor DM, Relman DA. The landscape ecology and microbiota of the human nose, mouth, and throat. Cell Host Microbe (2017) 21(4):421–32. 10.1016/j.chom.2017.03.011
    1. Huang S, Haiminen N, Carrieri A-P, Hu R, Jiang L, Parida L, et al. . Human Skin, Oral, and Gut Microbiomes Predict Chronological Age. mSystems (2020) 5(1):e00630–19. 10.1128/mSystems.00630-19
    1. Freire M, Moustafa A, Harkins DM, Torralba MG, Zhang Y, Leong P, et al. . Longitudinal Study of oral Microbiome Variation in twins. Sci Rep (2020) 10(1):1–10. 10.1038/s41598-020-64747-1
    1. Holgerson PL, Esberg A, Sjödin A, West CE, Johansson I. A longitudinal study of the development of the saliva microbiome in infants 2 days to 5 years compared to the microbiome in adolescents. Sci Rep (2020) 10(1):1–14. 10.1038/s41598-020-66658-7
    1. Mason MR, Chambers S, Dabdoub SM, Thikkurissy S, Kumar PS. Characterizing oral microbial communities across dentition states and colonization niches. Microbiome (2018) 6(1):67. 10.1186/s40168-018-0443-2
    1. Holgerson PL, Öhman C, Rönnlund A, Johansson I. Maturation of oral microbiota in children with or without dental caries. PLoS One (2015) 10(5):e0128534. 10.1371/journal.pone.0128534
    1. Tuominen H, Collado MC, Rautava J, Syrjänen S, Rautava S. Composition and maternal origin of the neonatal oral cavity microbiota. J Oral Microbiol (2019) 11(1):1663084. 10.1080/20002297.2019.1663084
    1. Uchiyama K, Haruyama Y, Shiraishi H, Katahira K, Abukawa D, Ishige T, et al. . Association between Passive Smoking from the Mother and Pediatric Crohn’s Disease: A Japanese Multicenter Study. Int J Environ Res Public Health (2020) 17(8):2926. 10.3390/ijerph17082926
    1. Kenney EB, Ash MM., Jr. Oxidation reduction potential of developing plaque, periodontal pockets and gingival sulci. J Periodontol (1969) 40(11):630–3. 10.1902/jop.1969.40.11.630
    1. Paster BJ, Boches SK, Galvin JL, Ericson RE, Lau CN, Levanos VA, et al. . Bacterial diversity in human subgingival plaque. J Bacteriol (2001) 183(12):3770–83. 10.1128/JB.183.12.3770-3783.2001
    1. Eggert F, Drewell L, Bigelow J, Speck J, Goldner M. The pH of gingival crevices and periodontal pockets in children, teenagers and adults. Arch Oral Biol (1991) 36(3):233–8. 10.1016/0003-9969(91)90091-8
    1. Marsh PD, Bradshaw DJ. Physiological approaches to the control of oral biofilms. Adv Dental Res (1997) 11(1):176–85. 10.1177/08959374970110010901
    1. Asikainen S, Doğan B, Turgut Z, Paster BJ, Bodur A, Oscarsson J. Specified species in gingival crevicular fluid predict bacterial diversity. PLoS One (2010) 5(10):e13589. 10.1371/journal.pone.0013589
    1. Zhou J, Yao Y, Jiao K, Zhang J, Zheng X, Wu F, et al. . Relationship between gingival crevicular fluid microbiota and cytokine profile in periodontal host homeostasis. Front Microbiol (2017) 8:2144. 10.3389/fmicb.2017.02144
    1. Liu S, Wang Y, Zhao L, Sun X, Feng Q. Microbiome succession with increasing age in three oral sites. Aging (2020) 12(9):7874. 10.18632/aging.103108
    1. Carpenter G. Salivary factors that maintain the normal oral commensal microflora. J Dental Res (2020) 99(6):644–9. 10.1177/0022034520915486
    1. Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol (2015) 15(1):30–44. 10.1038/nri3785
    1. Lourenςo TGB, Spencer SJ, Alm EJ, Colombo APV. Defining the gut microbiota in individuals with periodontal diseases: an exploratory study. J Oral Microbiol (2018) 10(1):1487741. 10.1080/20002297.2018.1487741
    1. Mall AS, Habte H, Mthembu Y, Peacocke J, De Beer C. Mucus and Mucins: do they have a role in the inhibition of the human immunodeficiency virus? Virol J (2017) 14(1):1–14. 10.1186/s12985-017-0855-9
    1. Olsen I, Yamazaki K. Can oral bacteria affect the microbiome of the gut? J Oral Microbiol (2019) 11(1):1586422. 10.1080/20002297.2019.1586422
    1. Arimatsu K, Yamada H, Miyazawa H, Minagawa T, Nakajima M, Ryder MI, et al. . Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota. Sci Rep (2014) 4:4828. 10.1038/srep04828
    1. Kitamoto S, Nagao-Kitamoto H, Hein R, Schmidt T, Kamada N. The Bacterial Connection between the Oral Cavity and the Gut Diseases. J Dental Res (2020) 99(9):1021–9. 10.1177/0022034520924633
    1. Nardone G, Compare D, Rocco A. A microbiota-centric view of diseases of the upper gastrointestinal tract. Lancet Gastroenterol Hepatol (2017) 2(4):298–312. 10.1016/S2468-1253(16)30108-X
    1. Pei Z, Bini EJ, Yang L, Zhou M, Francois F, Blaser MJ. Bacterial biota in the human distal esophagus. Proc Natl Acad Sci (2004) 101(12):4250–5. 10.1073/pnas.0306398101
    1. Muhlebach MS, Zorn BT, Esther CR, Hatch JE, Murray CP, Turkovic L, et al. . Initial acquisition and succession of the cystic fibrosis lung microbiome is associated with disease progression in infants and preschool children. PLoS Pathog (2018) 14(1):e1006798. 10.1371/journal.ppat.1006798
    1. 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(3):382–92. 10.1016/j.chom.2014.02.005
    1. Yachida S, Mizutani S, Shiroma H, Shiba S, Nakajima T, Sakamoto T, et al. . Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer. Nat Med (2019) 25(6):968–76. 10.1038/s41591-019-0458-7
    1. Schmidt TS, Hayward MR, Coelho LP, Li SS, Costea PI, Voigt AY, et al. . Extensive transmission of microbes along the gastrointestinal tract. eLife (2019) 8:e42693. 10.7554/eLife.42693
    1. Li B, Ge Y, Cheng L, Zeng B, Yu J, Peng X, et al. . Oral bacteria colonize and compete with gut microbiota in gnotobiotic mice. Int J Oral Sci (2019) 11(1):1–9. 10.1038/s41368-018-0043-9
    1. Zeller G, Tap J, Voigt AY, Sunagawa S, Kultima JR, Costea PI, et al. . Potential of fecal microbiota for early-stage detection of colorectal cancer. Mol Syst Biol (2014) 10(11):766. 10.15252/msb.20145645
    1. Dickson RP, Erb-Downward JR, Freeman CM, McCloskey L, Falkowski NR, Huffnagle GB, et al. . Bacterial topography of the healthy human lower respiratory tract. MBio (2017) 8(1):e02287–02216. 10.1128/mBio.02287-16
    1. Dinakaran V, Mandape SN, Shuba K, Pratap S, Sakhare SS, Tabatabai MA, et al. . Identification of specific oral and gut pathogens in full thickness colon of colitis patients: implications for colon motility. Front Microbiol (2019) 9:3220. 10.3389/fmicb.2018.03220
    1. White G. Oral health: A window into general health. J Oral Biol (2014) 1(1):5. 10.13188/2377-987X.1000002
    1. Oz HS, Chen T, Ebersole JL. A model for chronic mucosal inflammation in IBD and periodontitis. Dig Dis Sci (2010) 55(8):2194–202. 10.1007/s10620-009-1031-x
    1. 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(12):1799–805. 10.1902/jop.2014.140316
    1. Vila AV, Imhann F, Collij V, Jankipersadsing SA, Gurry T, Mujagic Z, et al. . Gut microbiota composition and functional changes in inflammatory bowel disease and irritable bowel syndrome. Sci Trans Med (2018) 10(472):eaap8914. 10.1126/scitranslmed.aap8914
    1. Lloyd-Price J, Arze C, Ananthakrishnan AN, Schirmer M, Avila-Pacheco J, Poon TW, et al. . Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases. Nature (2019) 569(7758):655–62. 10.1038/s41586-019-1237-9
    1. Sberro H, Fremin BJ, Zlitni S, Edfors F, Greenfield N, Snyder MP, et al. . Large-scale analyses of human microbiomes reveal thousands of small, novel genes. Cell (2019) 178(5):1245–59.e1214. 10.1016/j.cell.2019.07.016
    1. Carr VR, Witherden EA, Lee S, Shoaie S, Mullany P, Proctor GB, et al. . Abundance and diversity of resistomes differ between healthy human oral cavities and gut. Nat Commun (2020) 11(1):1–10. 10.1038/s41467-020-14422-w
    1. Proctor LM, Creasy HH, Fettweis JM, Lloyd-Price J, Mahurkar A, Zhou W, et al. . The integrative human microbiome project. Nature (2019) 569(7758):641–8. 10.1038/s41586-019-1238-8
    1. Sasaki N, Miyamoto K, Maslowski KM, Ohno H, Kanai T, Sato T. Development of a scalable co-culture system for gut anaerobes and human colon epithelium. Gastroenterology (2020) 159(1):388–90.e5. 10.1053/j.gastro.2020.03.021
    1. Irving J, Socransky S, Heeley J. Histological changes in experimental periodontal disease in gnotobiotic rats and conventional hamsters. J Periodontal Res (1974) 9(2):73–80. 10.1111/j.1600-0765.1974.tb00656.x
    1. Agossa K, Dendooven A, Dubuquoy L, Gower-Rousseau C, Delcourt-Debruyne E, Capron M. Periodontal manifestations of inflammatory bowel disease: emerging epidemiologic and biologic evidence. J Periodontal Res (2017) 52(3):313–24. 10.1111/jre.12422
    1. Marchesan J, Girnary MS, Jing L, Miao MZ, Zhang S, Sun L, et al. . An experimental murine model to study periodontitis. Nat Protoc (2018) 13(10):2247–67. 10.1038/s41596-018-0035-4
    1. Ebersole J, Kirakodu S, Chen J, Nagarajan R, Gonzalez O. Oral microbiome and gingival transcriptome profiles of ligature-induced periodontitis. J Dental Res (2020) 99(6):746–57. 10.1177/0022034520906138
    1. Spekhorst LM, Imhann F, Festen EA, Van Bodegraven AA, de Boer NK, Bouma G, et al. . Cohort profile: design and first results of the Dutch IBD Biobank: a prospective, nationwide biobank of patients with inflammatory bowel disease. BMJ Open (2017) 7(11):e016695. 10.1136/bmjopen-2017-016695
    1. Smillie CS, Biton M, Ordovas-Montanes J, Sullivan KM, Burgin G, Graham DB, et al. . Intra-and inter-cellular rewiring of the human colon during ulcerative colitis. Cell (2019) 178(3):714–30.e722. 10.1016/j.cell.2019.06.029
    1. Tang Z-Z, Chen G, Hong Q, Huang S, Smith HM, Shah RD, et al. . Multi-omic analysis of the microbiome and metabolome in healthy subjects reveals microbiome-dependent relationships between diet and metabolites. Front Genet (2019) 10:454. 10.3389/fgene.2019.00454
    1. Falvey JD, Hoskin T, Meijer B, Ashcroft A, Walmsley R, Day AS, et al. . Disease activity assessment in IBD: clinical indices and biomarkers fail to predict endoscopic remission. Inflamm Bowel Dis (2015) 21(4):824–31. 10.1097/mib.0000000000000341
    1. Kugathasan S, Denson LA, Walters TD, Kim M-O, Marigorta UM, Schirmer M, et al. . Prediction of complicated disease course for children newly diagnosed with Crohn’s disease: a multicentre inception cohort study. Lancet (2017) 389(10080):1710–8.
    1. Martin JC, Chang C, Boschetti G, Ungaro R, Giri M, Grout JA, et al. . Single-cell analysis of Crohn’s disease lesions identifies a pathogenic cellular module associated with resistance to anti-TNF therapy. Cell (2019) 178(6):1493–508.e1420. 10.1016/j.cell.2019.08.008
    1. Chen Y, Chen X, Yu H, Zhou H, Xu S. Oral Microbiota as Promising Diagnostic Biomarkers for Gastrointestinal Cancer: A Systematic Review. OncoTargets Ther (2019) 12:11131. 10.2147/OTT.S230262
    1. Liebsch C, Pitchika V, Pink C, Samietz S, Kastenmüller G, Artati A, et al. . The saliva metabolome in association to oral health status. J Dental Res (2019) 98(6):642–51. 10.1177/0022034519842853

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren