Pathogenic associations between oral and gastrointestinal diseases

Inflammatory bowel disease and periodontitis are associated in epidemiologic studies.Both complex conditions involve microbial and host immune system interactions that create chronic inflammation and tissue damage in susceptible individuals.Emerging evidence shows a link between oral inflammation and gut inflammation through direct and indirect mechanisms, including hematologic and lymphatic trafficking of activated T cells and enteric transmission of inflammatory bacteria.There is a need for prospective interventional research to determine the clinical implications of these findings. Both periodontitis and inflammatory bowel disease (IBD) are complex chronic conditions characterized by aberrant host immune response and dysregulated microbiota. Emerging data show an association between periodontitis and IBD, including direct and indirect mechanistic links between oral and intestinal inflammation. Direct pathways include translocation of proinflammatory microbes from the oral cavity to the gut and immune priming. Indirect pathways involve systemic immune activation with possible nonspecific effects on the gut. There are limited data on the effects of periodontal disease treatment on IBD course and vice versa, but early reports suggest that treatment of periodontitis decreases systemic immune activation and that treatment of IBD is associated with periodontitis healing, underscoring the importance of recognizing and treating both conditions. Both periodontitis and inflammatory bowel disease (IBD) are complex chronic conditions characterized by aberrant host immune response and dysregulated microbiota. Emerging data show an association between periodontitis and IBD, including direct and indirect mechanistic links between oral and intestinal inflammation. Direct pathways include translocation of proinflammatory microbes from the oral cavity to the gut and immune priming. Indirect pathways involve systemic immune activation with possible nonspecific effects on the gut. There are limited data on the effects of periodontal disease treatment on IBD course and vice versa, but early reports suggest that treatment of periodontitis decreases systemic immune activation and that treatment of IBD is associated with periodontitis healing, underscoring the importance of recognizing and treating both conditions. The oral–gut axis is an area of emerging interest because of the high burden of oral disease and recent discoveries elucidating the interplay between inflammation, the microbiome (see Glossary), and chronic disease in these related sites [1.Peres M.A. et al.Oral diseases: a global public health challenge.Lancet. 2019; 394: 249-260Abstract Full Text Full Text PDF PubMed Scopus (884) Google Scholar,2.Kitamoto S. et al.The bacterial connection between the oral cavity and the gut diseases.J. Dent. Res. 2020; 99: 1021-1029Crossref PubMed Scopus (72) Google Scholar]. Prior epidemiologic research has identified associations between oral health and a variety of medical conditions [3.Jin L.J. et al.Global burden of oral diseases: emerging concepts, management and interplay with systemic health.Oral Dis. 2016; 22: 609-619Crossref PubMed Scopus (311) Google Scholar]. In this review, we will focus on the relationship between periodontitis and inflammatory bowel disease (IBD). Periodontal disease is characterized by chronic inflammation affecting the bone and tissues around the tooth. This develops initially as gingivitis, a reversible inflammation of the gums and soft tissues around the tooth, and it progresses to involve the bone, cementum, and periodontal ligament. The causes of periodontitis are multifactorial but lead to chronic inflammation with progressive tissue destruction, exposing deeper structures to the oral microbiome, which leads to further host immune activation. Periodontitis is one of the most prevalent conditions worldwide [4.Marcenes W. et al.Global burden of oral conditions in 1990-2010: a systematic analysis.J. Dent. Res. 2013; 92: 592-597Crossref PubMed Scopus (938) Google Scholar]. There is limited high-quality data on the international prevalence and trends in periodontal disease. The global prevalence of periodontitis is estimated to be 11.2% and increases with age [3.Jin L.J. et al.Global burden of oral diseases: emerging concepts, management and interplay with systemic health.Oral Dis. 2016; 22: 609-619Crossref PubMed Scopus (311) Google Scholar, 4.Marcenes W. et al.Global burden of oral conditions in 1990-2010: a systematic analysis.J. Dent. Res. 2013; 92: 592-597Crossref PubMed Scopus (938) Google Scholar, 5.Kassebaum N.J. et al.Global burden of severe periodontitis in 1990-2010: a systematic review and meta-regression.J. Dent. 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Despite these research challenges, data suggest that the prevalence of severe tooth loss (i.e., edentulism) is decreasing while the prevalence of advanced periodontitis is increasing, likely because of increasing longevity and improved preventive dental care that limits tooth loss [4.Marcenes W. et al.Global burden of oral conditions in 1990-2010: a systematic analysis.J. Dent. Res. 2013; 92: 592-597Crossref PubMed Scopus (938) Google Scholar,5.Kassebaum N.J. et al.Global burden of severe periodontitis in 1990-2010: a systematic review and meta-regression.J. Dent. Res. 2014; 93: 1045-1053Crossref PubMed Scopus (1072) Google Scholar,8.Kassebaum N.J. et al.Global burden of severe tooth loss: a systematic review and meta-analysis.J. Dent. Res. 2014; 93: 20S-28SCrossref PubMed Scopus (330) Google Scholar]. In the US, an estimated 42% of all community-dwelling adults aged 30 years and older have periodontal disease and 7.8% of the population has severe periodontitis [6.Eke P.I. et al.Recent epidemiologic trends in periodontitis in the USA.Periodontol. 2000. 2020; 82: 257-267Crossref PubMed Scopus (116) Google Scholar]. Longitudinal Scandinavian data show that overall rates of periodontal disease are improving in highly developed countries, though the percentage of the population with severe disease has remained stable [9.Gjermo P.E. Impact of periodontal preventive programmes on the data from epidemiologic studies.J. Clin. Periodontol. 2005; 32: 294-300Crossref PubMed Google Scholar, 10.Hugoson A. et al.Trends over 30 years, 1973-2003, in the prevalence and severity of periodontal disease.J. Clin. Periodontol. 2008; 35: 405-414Crossref PubMed Scopus (165) Google Scholar, 11.Skudutyte-Rysstad R. et al.Trends in periodontal health among 35-year-olds in Oslo, 1973-2003.J. Clin. 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Clin. Periodontol. 2021; 48: 627-637Crossref PubMed Scopus (9) Google Scholar]. There are limited data for other regions. IBD is a set of idiopathic chronic inflammatory disorders affecting the gastrointestinal (GI) tract. It includes two main types, Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis of IBD is multifactorial, involving both host and environmental factors, such as genetics, diet, stress, and the microbiome [16.Caruso R. et al.Host-microbiota interactions in inflammatory bowel disease.Nat. Rev. Immunol. 2020; 20: 411-426Crossref PubMed Scopus (187) Google Scholar]. CD is characterized by chronic transmural mucosal inflammation that can occur throughout the GI tract from mouth to anus, at times in a discontinuous pattern. Inflammation in UC is limited to the mucosa and occurs in a contiguous fashion in the colon, starting at the rectum, though there can be some involvement of the terminal ileum. The mouth is a common extra-intestinal site of IBD involvement, suggesting a role for the oral–gut immune and microbiome axis in pathogenesis. Previously, CD was felt to be a Th1 cell-predominant process, whereas UC was Th2-driven, though work on Th17 cells has led to a more complex understanding of these diseases [17.Brand S. Crohn's disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease.Gut. 2009; 58: 1152-1167Crossref PubMed Scopus (492) Google Scholar]. In the USA, IBD affects an estimated 1.3% of adults [18.Dahlhamer J.M. et al.Prevalence of inflammatory bowel disease among adults aged >/=18 years - United States, 2015.MMWR Morb. Mortal. Wkly Rep. 2016; 65: 1166-1169Crossref PubMed Scopus (319) Google Scholar]. Globally, the incidence of IBD varies but has been increasing [19.Mak W.Y. et al.The epidemiology of inflammatory bowel disease: east meets west.J. Gastroenterol. Hepatol. 2020; 35: 380-389Crossref PubMed Scopus (143) Google Scholar,20.Collaborators, G.B.D.I.B.DThe 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: 17-30Abstract Full Text Full Text PDF PubMed Scopus (614) Google Scholar]. In the past 25 years, IBD incidence in highly developed countries has risen slowly or plateaued [21.Shivashankar R. et al.Incidence and prevalence of Crohn's disease and ulcerative colitis in Olmsted County, Minnesota from 1970 through 2010.Clin. Gastroenterol. Hepatol. 2017; 15: 857-863Abstract Full Text Full Text PDF PubMed Scopus (225) Google Scholar,22.Bitton A. et al.Epidemiology of inflammatory bowel disease in Quebec: recent trends.Inflamm. Bowel Dis. 2014; 20: 1770-1776Crossref PubMed Scopus (47) Google Scholar]. However in Asia, IBD incidence has increased dramatically, with some countries reporting rates that doubled or tripled in the same time frame [23.Kim H.J. et al.Incidence and natural course of inflammatory bowel disease in Korea, 2006-2012: a nationwide population-based study.Inflamm. Bowel Dis. 2015; 21: 623-630Crossref PubMed Scopus (118) Google Scholar,24.Ng S.C. et al.Incidence and phenotype of inflammatory bowel disease based on results from the Asia-pacific Crohn's and colitis epidemiology study.Gastroenterology. 2013; 145: 158-165Abstract Full Text Full Text PDF PubMed Scopus (537) Google Scholar]. The highest age-standardized prevalence of IBD is in high-income areas of North America (422.0 cases per 100 000), whereas the lowest is in the Caribbean (6.7 per 100 000 population) [20.Collaborators, G.B.D.I.B.DThe 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: 17-30Abstract Full Text Full Text PDF PubMed Scopus (614) Google Scholar]. The mechanisms by which periodontal disease may cause or exacerbate chronic GI diseases are complex. We will discuss the epidemiologic evidence supporting an association between periodontitis and IBD, emerging research on the pathways behind these associations, controversies in the field, and future directions. On an epidemiologic level, multiple studies have demonstrated a strong association between IBD and periodontal disease (Table 1). Three recent meta-analyses found that periodontitis is associated with both CD and UC, with pooled odds ratios of 1.7–3.6 for CD and 2.4–5.4 for UC [25.Lorenzo-Pouso A.I. et al.Association between periodontal disease and inflammatory bowel disease: a systematic review and meta-analysis.Acta Odontol. Scand. 2021; 79: 344-353Crossref PubMed Scopus (12) Google Scholar, 26.She Y.Y. et al.Periodontitis and inflammatory bowel disease: a meta-analysis.BMC Oral Health. 2020; 20: 67Crossref PubMed Scopus (39) Google Scholar, 27.Zhang Y. et al.The association between periodontitis and inflammatory bowel disease: a systematic review and meta-analysis.Biomed. Res. Int. 2021; 20216692420Google Scholar]. This association is seen both in adults as well as children and adolescents with IBD [28.Koutsochristou V. et al.Dental caries and periodontal disease in children and adolescents with inflammatory bowel disease: a case-control study.Inflamm. Bowel Dis. 2015; 21: 1839-1846Crossref PubMed Scopus (40) Google Scholar]. Individuals with IBD are more likely to have had dental treatments and have worse perceived oral health than healthy controls [29.Rikardsson S. et al.Perceived oral health in patients with Crohn's disease.Oral Health Prev. Dent. 2009; 7: 277-282PubMed Google Scholar,30.Kato I. et al.History of inflammatory bowel disease and self-reported oral health: women's health initiative observational study.J. Women's Health (Larchmt). 2020; 29: 1032-1040Crossref PubMed Scopus (2) Google Scholar]. This may be based on a greater need for dental procedures among individuals with IBD as compared with those without IBD, as was found in a Swedish cohort study [31.Johannsen A. et al.Consumption of dental treatment in patients with inflammatory bowel disease, a register study.PLoS One. 2015; 10e0134001Crossref Scopus (15) Google Scholar].Table 1Studies of periodontitis and IBDCountryDesignIBD patients (n)Healthy controls (n)Periodontitis measuresFindingsRefsTaiwanCohort6657 (CD)26 628Billing codesCD patients at increased risk of developing periodontitis (HR 1.36)[68.Chi Y.C. et al.Increased risk of periodontitis among patients with Crohn's disease: a population-based matched-cohort study.Int. J. Color. Dis. 2018; 33: 1437-1444Crossref PubMed Scopus (17) Google Scholar]SwedenCohort3161 (CD) and 2085 (UC)5246Dental care utilizationCD and UC patients had higher numbers of dental procedures following diagnosis, including more total procedures and fillings.[31.Johannsen A. et al.Consumption of dental treatment in patients with inflammatory bowel disease, a register study.PLoS One. 2015; 10e0134001Crossref Scopus (15) Google Scholar]KoreaCohort9 950 548 overall (IBD and no IBD)Oral screening examPeriodontitis associated with increased risk of UC development (aHR 1.091) but not CD (aHR 0.879).[32.Kang E.A. et al.Periodontitis combined with smoking increases risk of the ulcerative colitis: a national cohort study.World J. Gastroenterol. 2020; 26: 5661-5672Crossref PubMed Scopus (11) Google Scholar]TaiwanCohort27 041 periodontal disease108 149 no periodontal diseaseBilling codesHR of IBD in both groups similar (HR 1.01), but increased risk of UC in periodontitis group after adjustment (aHR 1.56)[34.Lin C.Y. et al.Increased risk of ulcerative colitis in patients with periodontal disease: a nationwide population-based cohort study.Int. J. Environ. Res. Public Health. 2018; 15: 2602Crossref Scopus (16) Google Scholar]SwedenCohort20 162 overall (IBD and no IBD)Oral exam at study entryTooth loss at baseline associated with lower risk of IBD development (HR 0.56). More plaque associated with lower CD risk (HR 0.32)[34.Lin C.Y. et al.Increased risk of ulcerative colitis in patients with periodontal disease: a nationwide population-based cohort study.Int. J. Environ. Res. Public Health. 2018; 15: 2602Crossref Scopus (16) Google Scholar]BrazilCross-sectional case-control179 (99 CD and 80 UC)74DMFT, PPD, CAL, BOP, plaque indexMore IBD patients had periodontitis than controls (81.8% CD, 90% UC, 67.6% controls).[79.Brito F. et al.Prevalence of periodontitis and DMFT index in patients with Crohn's disease and ulcerative colitis.J. Clin. Periodontol. 2008; 35: 555-560Crossref PubMed Scopus (91) Google Scholar]JapanCross-sectional case-control60 (18 CD and 42 UC)45BOP, caries, PPDNo difference in periodontitis or caries between IBD and control groups.[37.Imai J. et al.A potential pathogenic association between periodontal disease and Crohn's disease.JCI Insight. 2021; 6e148543Crossref Scopus (6) Google Scholar]GermanyCross-sectional case-control62 (IBD type not specified)59DMFS, caries, plaque index, BOP, PPD, CALNo difference in DMFS between groups but more dental caries and CAL in IBD group.[80.Grossner-Schreiber B. et al.Prevalence of dental caries and periodontal disease in patients with inflammatory bowel disease: a case-control study.J. Clin. Periodontol. 2006; 33: 478-484Crossref PubMed Scopus (71) Google Scholar]JordanCross-sectional case-control160 (59 CD and 101 UC)100PPD, GR, LA, BOP, plaque index, gingival indexHigher prevalence of periodontitis in IBD group <45 years old and in adjusted analysis (OR for CD 4.9, OR for UC 7.0), and more severe periodontitis in IBD group.[81.Habashneh R.A. et al.The association between inflammatory bowel disease and periodontitis among Jordanians: a case-control study.J. Periodontal Res. 2012; 47: 293-298Crossref PubMed Scopus (64) Google Scholar]GreeceCross-sectional case-control55 (36 CD and 19 UC)55DMFT, gingival index, plaque index, periodontitis treatment needsDMFT, gingival inflammation both higher in IBD. No difference in plaque index. Higher periodontal treatment needs in IBD group.[28.Koutsochristou V. et al.Dental caries and periodontal disease in children and adolescents with inflammatory bowel disease: a case-control study.Inflamm. Bowel Dis. 2015; 21: 1839-1846Crossref PubMed Scopus (40) Google Scholar]ItalyCross-sectional case-control110 (IBD type not specified)110DMFT, PAIDMFT and prevalence of apical periodontitis similar between IBD and control groups but higher PAI in IBD group.[82.Piras V. et al.Prevalence of apical periodontitis in patients with inflammatory bowel diseases: a retrospective clinical study.J. Endod. 2017; 43: 389-394Abstract Full Text Full Text PDF PubMed Scopus (29) Google Scholar]SpainCross-sectional case-control54 (28 CD and 26 UC)54RPL, PAI, RFTMore RPL in IBD group (35.2% versus 16.7%), no difference in number of teeth with apical periodontitis or number of RFT[83.Poyato-Borrego M. et al.High prevalence of apical periodontitis in patients with inflammatory bowel disease: an age- and gender- matched case-control study.Inflamm. Bowel Dis. 2020; 26: 273-279Crossref PubMed Scopus (19) Google Scholar]GermanyCross-sectional case-control59 (30 CD and 29 UC)59DMFT, PPD, BOP, CALIBD patients had higher CAL, more severe periodontitis, and more gingival bleeding.[84.Schmidt J. et al.Active matrix metalloproteinase-8 and periodontal bacteria-interlink between periodontitis and inflammatory bowel disease?.J. Periodontol. 2018; 89: 699-707Crossref PubMed Scopus (18) Google Scholar]SwedenCross-sectional case-control150 (71 CD with prior intestinal surgery and 79 CD no surgery)75DMFT, DMFS, salivary flow, dental plaqueCD with prior resection had higher DMFS and more plaque than controls.[85.Szymanska S. et al.Dental caries, prevalence and risk factors in patients with Crohn's disease.PLoS One. 2014; 9e91059Crossref Scopus (23) Google Scholar]NetherlandsCross-sectional case-control229 (148 CD, 80 UC, 1 IBD undetermined)229DMFT, DPSIDMFT higher in IBD group. DMFT higher for CD than controls but not for UC. DPSI not different between IBD and control groups, but more IBD patients edentulous[86.Tan C.X.W. et al.Dental and periodontal disease in patients with inflammatory bowel disease.Clin. Oral Investig. 2021; 25: 5273-5280Crossref PubMed Scopus (10) Google Scholar]SwitzerlandCross-sectional case-control113 (69 CD and 44 UC)113DMFT, PPD, PBI, LA, PPD, BOPWorse DMFT, PBI, LA-PPD, BOP in IBD. In CD group, clinical activity (HBI) associated with worse LA-PPD; perianal disease associated with BOP.[87.Vavricka S.R. et al.Periodontitis and gingivitis in inflammatory bowel disease: a case-control study.Inflamm. Bowel Dis. 2013; 19: 2768-2777Crossref PubMed Scopus (75) Google Scholar]GreeceCross-sectional case-control30 (15 CD and 15 UC)47Appearance of periodontitis, gingivitis, BOP, other lesionsHigher rates of oral lesions in IBD group (87% CD, 93% UC, 55% control group). More periodontitis and BOP in CD compared with controls.[88.Zervou F. et al.Oral manifestations of patients with inflammatory bowel disease.Ann. Gastroenterol. 2004; 17: 395-401Google Scholar]ChinaCross-sectional case-control389 (265 CD and 124 UC)265DMFT, DMFS, PPD, CAL, BOP, GR, gingival index, plaque index, CALDMFS increased in IBD versus controls (OR 4.27 for CD, 2.21 for UC). Higher risk of dental caries, probing pocket depth ≥5 mm, CAL ≥4 mm in IBD group.[89.Zhang L. et al.Increased risks of dental caries and periodontal disease in Chinese patients with inflammatory bowel disease.Int. Dent. J. 2020; 70: 227-236Crossref PubMed Scopus (23) Google Scholar]Studies of perceived oral health and behaviorsUnited StatesCross-sectional case-control880 (IBD type not specified)72 741Oral health questionnaireSelf-reported periodontal disease not associated with IBD. Poorer self-rated oral health and eating limitations due to teeth more common in IBD group (OR 1.15 and 1.22, respectively)[30.Kato I. et al.History of inflammatory bowel disease and self-reported oral health: women's health initiative observational study.J. Women's Health (Larchmt). 2020; 29: 1032-1040Crossref PubMed Scopus (2) Google Scholar]SwedenCross-sectional case-control1598 (all CD)748Oral health questionnaireIBD patients rate worse oral health and greater need for dental treatment after controlling for age, smoking, gender, and education.[29.Rikardsson S. et al.Perceived oral health in patients with Crohn's disease.Oral Health Prev. Dent. 2009; 7: 277-282PubMed Google Scholar]United StatesCross-sectional case-control83 (57 CD and 26 UC)54Oral health questionnaireHigher frequency of brushing and flossing at disease onset in IBD patients. More frequent dental visits, more caries.[90.Singhal S. et al.The role of oral hygiene in inflammatory bowel disease.Dig. Dis. Sci. 2011; 56: 170-175Crossref PubMed Scopus (40) Google Scholar]Abbreviations: aHR, adjusted hazard ratio; BOP, bleeding on probing; CAL, calculus index; CD, Crohn's disease; DMFS, decayed missing filled surfaces; DMFT, decayed missing filled teeth; DPSI, Dutch Periodontal Screening Index; GR, gingival recession; HR, hazard ratio; IBD, inflammatory bowel disease; LA, loss of attachment; HBI, Harvey–Bradshaw index; OR, odds ratio; PAI, periapical index; PBI, papilla bleeding index; PPD, probing pocket depth; RFT, root filled tooth; RPL, radiographic radiolucent periapical lesions; UC, ulcerative colitis. Open table in a new tab Abbreviations: aHR, adjusted hazard ratio; BOP, bleeding on probing; CAL, calculus index; CD, Crohn's disease; DMFS, decayed missing filled surfaces; DMFT, decayed missing filled teeth; DPSI, Dutch Periodontal Screening Index; GR, gingival recession; HR, hazard ratio; IBD, inflammatory bowel disease; LA, loss of attachment; HBI, Harvey–Bradshaw index; OR, odds ratio; PAI, periapical index; PBI, papilla bleeding index; PPD, probing pocket depth; RFT, root filled tooth; RPL, radiographic radiolucent periapical lesions; UC, ulcerative colitis. However, a major challenge in understanding the causal pathways implicated is that most epidemiologic studies of periodontal disease and IBD have been cross-sectional rather than longitudinal. Some of the larger cohort studies on this topic report mixed results. A retrospective cohort study in Korea showed that periodontal disease was associated with an increased risk of a new diagnosis of UC but not of CD [32.Kang E.A. et al.Periodontitis combined with smoking increases risk of the ulcerative colitis: a national cohort study.World J. Gastroenterol. 2020; 26: 5661-5672Crossref PubMed Scopus (11) Google Scholar]. In a 20 000-patient retrospective cohort from Sweden, poor dental hygiene and tooth loss were associated with lower risk of IBD; loss of five to six teeth was associated with a 50% lower risk of developing IBD and high dental plaque burden was associated a 70% lower risk of development of CD, though plaque burden was not associated with UC [33.Yin W. et al.Inverse association between poor oral health and inflammatory bowel diseases.Clin. Gastroenterol. Hepatol. 2017; 15: 525-531Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar]. In a Taiwanese cohort study of individuals with periodontitis, there was an increased risk of development of UC (adjusted hazard ratio 1.56) but not of CD [34.Lin C.Y. et al.Increased risk of ulcerative colitis in patients with periodontal disease: a nationwide population-based cohort study.Int. J. Environ. Res. Public Health. 2018; 15: 2602Crossref Scopus (16) Google Scholar]. Taken collectively, these studies suggest a link but that standardized prospective studies are needed. The link between periodontal disease and IBD is further supported by the changes seen in both the oral and gut microbiome of individuals with IBD [35.Kitamoto S. Kamada N. Periodontal connection with intestinal inflammation: microbiological and immunological mechanisms.Periodontol 2000. 2022; 89: 142-153Crossref PubMed Scopus (2) Google Scholar,36.Read E. et al.The role of oral bacteria in inflammatory bowel disease.Nat. Rev. Gastroenterol. Hepatol. 2021; 18: 731-742Crossref PubMed Scopus (23) Google Scholar]. When compared with healthy controls, individuals with IBD have altered gut and salivary microbiomes, often referred to as dysbiosis. This is accompanied by failures of mucosal immunity and a loss of symbiotic relationships between bacteria and the human host, which leads to inflammation and illness [16.Caruso R. et al.Host-microbiota interactions in inflammatory bowel disease.Nat. Rev. Immunol. 2020; 20: 411-426Crossref PubMed Scopus (187) Google Scholar]. One characteristic of the dysbiotic gut microbiome in IBD is a greater resemblance to the oral microbiome or 'oralization' of the gut microbiome [37.Imai J. et al.A potential pathogenic association between periodontal disease and Crohn's disease.JCI Insight. 2021; 6e148543Crossref Scopus (6) Google Scholar]. This includes enrichment of typically oral bacteria such as Fusobacteriaceae, Pasteurellaceae, Klebsiella spp. and Veillonellaceae and loss of more typical gut bacteria, like Faecalibacterium prausnitzii [2.Kitamoto S. et al.The bacterial connection between the oral cavity and the gut diseases.J. Dent. Res. 2020; 99: 1021-1029Crossref PubMed Scopus (72) Google Scholar,37.Imai J. et al.A potential pathogenic association between periodontal disease and Crohn's disease.JCI Insight. 2021; 6e148543Crossref Scopus (6) Google Scholar, 38.Said H.S. et al.Dysbiosis of salivary microbiota in inflammatory bowel disease and its association with oral immunological biomarkers.DNA Res. 2014; 21: 15-25Crossref PubMed Scopus (239) Google Scholar, 39.Cai Z. et al.Co-pathogens in periodontitis and inflammatory bowel disease.Front. Med. (Lausanne). 2021; 8723719Google Scholar]. Patients with IBD also experience salivary dysbiosis, with increased Bacteroidetes, which is associated with increased salivary inflammatory cytokines [38.Said H.S. et al.Dysbiosis of salivary microbiota in inflammatory bowel disease and its association with oral immunological biomarkers.DNA Res. 2014; 21: 15-25Crossref PubMed Scopus (239) Google Scholar]. Small studies have reported that salivary dysbiosis in IBD may correlate with IBD activity, suggesting a reciprocal relationship [40.Somineni H.K. et al.Site- and taxa-specific disease-associated oral microbial structures distinguish inflammatory bowel diseases.Inflamm. Bowel Dis. 2021; 27: 1889-1900Crossref PubMed Scopus (3) Google Scholar,41.Hu S. et al.Ectopic gut colonization: a metagenomic study of the oral and gut microbiome in Crohn's disease.Gut Pathog. 2021; 13: 13Crossref PubMed Scopus (10) Google Scholar]. The mechanisms of oral–gut microbiome interaction in IBD are an area of active clinical and translational investigation. Current hypotheses are based on observations from translational research in humans and animal models of IBD. The working theory is that there are both direct and indirect pathways of oral–gut interaction that depend on both the microbiome and immune cell activation to synergistically promote inflammation in susceptible individuals (Figure 1). These may operate in a series of steps that gradually establish the conditions necessary for ectopic bacterial colonization and promote a hyperactive immune response [36.Read E. et al.The role of oral bacteria in inflammatory bowel disease.Nat. Rev. Gastroenterol. Hepatol. 2021; 18: 731-742Crossref PubMed Scopus (23) Google Scholar]. Underlying factors that may predispose to increased intestinal inflammation from periodontitis are not fully understood. However, a disruption or instability of the healthy microbiome is necessary to allow for ectopic gut colonization by oral pathobionts. Host genetic variants