The Gum-Gut Connection: Understanding the relationship between the oral and GI microbiomes is essential to disease prevention and management

Steven R. Sheibley, DMD; and Maria L. Geisinger, DDS, MS

April 2024 Issue - Expires Friday, April 30th, 2027

Inside Dentistry

Abstract

Over the last several years, the gum-gut connection has emerged as a critical concept addressing the relationship between the oral and gut microbiomes and how this relationship impacts oral and systemic disease. This emerging area of study emphasizes the significance of systemic health and the importance of recognizing the contribution of oral health as a critical piece of that system. The relationship between the oral and GI microbiomes is bidirectional and mediated through various mechanisms. Disruptions in either the oral or GI microbiome may result in a shift from eubiosis to dysbiosis that can affect the other microbiome through microbial transfer or inflammatory responses that have far-reaching consequences. This article examines the relationships between the oral and GI microbiomes and their implications for oral and general health, reviews inflammatory processes at local and systemic levels, identifies risk factors for worsening conditions, and discusses how these relationships can be manipulated to improve patient health through patient education and various interventions.

You must be signed in to read the rest of this article.

Login Sign Up

Registration on CDEWorld is free. You may also login to CDEWorld with your DentalAegis.com account.

The "gum-gut connection" is a concept that is garnering increasing attention within the fields of dentistry and healthcare in recent years.1,2 It underscores the intricate and dynamic relationship between two vital microbial ecosystems in the human body: the oral microbiome and the gastrointestinal (GI) microbiome. Because this connection has profound implications for overall well-being, understanding it is of paramount importance for dental healthcare professionals.

The Oral Microbiome and Oral Disease

The oral microbiome, a diverse community of microorganisms inhabiting various oral niches, is primarily composed of bacteria, viruses, and fungi.3 These microorganisms coexist in a delicate equilibrium, and factors such as inadequate oral hygiene practices, poor dietary intake, systemic disease, poor salivary flow, or smoking can result in disruptions to this balance.4 Such disruptions may result in a shift from eubiosis to dysbiosis. In the context of periodontal health and disease, a shift from eubiosis to dysbiosis represents a significant transformation in the oral microbiome. In a state of eubiosis, the oral microbiome is characterized by a balanced and diverse community of microorganisms, including both beneficial and, in a smaller proportion, potentially harmful species. This equilibrium, which is actively regulated by the host immune system, is crucial for the maintenance of oral health because beneficial bacteria play a role in suppressing the growth of their pathogenic counterparts.5,6

In eubiosis, the relationship between the host and these microorganisms is symbiotic, promoting oral health. However, as dental plaque accumulates and matures, a shift toward dysbiosis can occur.7,8 Dysbiosis is characterized by an overgrowth of pathogenic bacteria, including F. nucleatum, P. gingivalis, T. denticola, and T. forsythia, and is often triggered by factors such as inadequate oral hygiene, poor dietary choices, smoking, or genetic predisposition.5,9 These pathogenic bacteria, which have previously been classified into the pathogenic periodontal orange and red complexes,10 can proliferate—outcompeting the beneficial bacteria and evading the host's immune response. A shift to dysbiosis may be gradual and multifactorial and is often associated with inflammation and tissue damage.9 When the equilibrium of the oral microbiome is disturbed, it can pave the way for the development of oral diseases, including dental caries and periodontal disease.11 Therefore, understanding how this transition occurs is fundamental in developing strategies to preserve eubiosis and prevent or manage the occurrence of oral disease.

It is important to note that the oral microbiome is not uniform throughout the oral cavity. For example, the environment and microbiota differ supragingivally versus subgingivally, and the conditions for microbial growth in interdental spaces differ from those by the mucosal lining of the cheeks or on the surface of the tongue.12,13 This diversity leads to a variety of oral environs and heterogeneous biofilm accumulation that is locally dependent.14

One contributing factor during a shift to dysbiosis is quorum sensing. Quorum sensing is a mechanism by which bacteria communicate using extracellular signaling molecules to enhance their pathogenicity and ability to elicit an immune response.15,16 This bacterial cross talk can impact the development of dysbiosis and oral diseases, such as dental caries and periodontitis, through several key mechanisms, including the coordinated formation of biofilms in the oral cavity.17 Such biofilm constitutes structured communities of bacteria encased in a protective matrix that not only repels external molecules but also holds the complex bacterial environment together. In the oral cavity, bacteria within a biofilm can be more resistant to host immune responses and traditional antimicrobial treatments when compared with planktonic organisms.18,19 Quorum sensing can also regulate the expression of virulence factors, enabling pathogenic bacteria to drive disease.17 In dental caries, virulence factors can promote the production of acids that damage tooth structure, whereas in periodontitis, they can facilitate tissue destruction and inflammation.10,20 This can lead to an exacerbation of the inflammation associated with periodontitis and other oral diseases while the key inflammatory cells are inhibited from penetrating the biofilm.21 Understanding these complex interactions is essential to the development of precise strategies to prevent and treat oral disease.

Microbial Etiology of Dental Caries and Periodontitis

Dental caries can result from an imbalance in the oral microbiome. The development of dental caries requires specific bacteria, such as S. mutans, to be in the presence of fermentable carbohydrates. Bacteria such as S. mutans metabolize dietary sugars, producing acids that result in periods of demineralization and remineralization and, ultimately, erosion of the enamel and dentin of the teeth, which can lead to dental caries. However, S. mutans generally does not exist in isolation. Individual bacterial species require a complex biofilm to survive in the oral environment. It should also be noted that some oral bacteria have been associated with a decreased risk of dental caries development.20

Periodontitis, which is also associated with oral dysbiosis, is defined in the American Academy of Periodontology's Glossary of Periodontal Terms as "inflammation of the periodontal tissues resulting in clinical attachment loss, alveolar bone loss, and periodontal pocketing." Periodontal disease primarily affects the tooth supporting periodontium.22 Dysbiosis of the oral microbiome, driven by factors such as poor oral hygiene, systemic disease, and smoking, can lead to the accumulation of bacterial biofilms involving more pathogenic microbes.9,23 This increase in pathogenic microbes can, in turn, trigger an inflammatory response by the host immune system, resulting in gingival inflammation, bleeding, and tissue destruction.24 If left untreated, advanced periodontal disease can lead to clinical attachment loss, tooth mobility, and ultimately, tooth loss.25,26

The GI Microbiome and Systemic Disease

The (GI) microbiome is found throughout the GI tract, and it plays a multifaceted role in human health. This microbial community is involved in digestion and the breakdown of complex carbohydrates, which produces essential nutrients and metabolites that benefit the host. Moreover, the GI microbiome is an integral player in regulating immune function and maintaining the integrity of the "gut barrier."27,28

Research has illuminated the GI microbiome's involvement in a spectrum of systemic diseases. Conditions such as diabetes, cardiovascular disease, irritable bowel syndrome (IBS), and Crohn's disease have been linked to imbalances in the GI microbiome.27-29 Oftentimes, these links hinge on the role of the GI microbiome in mediating inflammation. Dysbiosis in the gut can promote inflammation, leading to insulin resistance and contributing to the development of diabetes and cardiovascular disease.26 Chronic inflammation, a common feature of many systemic diseases, can be triggered or exacerbated by imbalances in the GI microbiome.30-32 Metabolic syndrome, which is characterized by obesity, hypertension, insulin resistance, and dyslipidemia, is tightly linked to systemic inflammation driven by the GI microbiome.28 In individuals with severe GI disease, the elimination of the endogenous GI microbiome via fecal microbiota transplantation with samples from an individual with a healthy GI microbiome has been shown to improve health outcomes.33,34

Implications of the Gum-Gut Connection

One of the most intriguing aspects of the gum-gut connection is the bidirectional relationship between the oral and GI microbiomes.29 This relationship is mediated through various mechanisms, which highlights the interconnectedness of the two microbial ecosystems. Microbial transfer plays a pivotal role in this connection. Bacteria from the oral cavity can be ingested and find their way into the GI tract, and because some of these oral bacteria are potentially pathogenic, their presence in the gut can influence the composition and diversity of the GI microbiome.35 Although the gut has its own resident microbial community, the introduction of oral bacteria can potentially disrupt its microbial balance, resulting in immune responses and inflammatory reactions (Figure 1).

Inflammatory responses, such as those associated with oral microbiome dysbiosis, can have far-reaching consequences. For example, chronic inflammation triggered by periodontal disease in the oral cavity can extend into the systemic circulation and impact various organs and tissues.36 This systemic inflammation can then, in turn, affect the GI microbiome, which further emphasizes the intricacy of the web of interactions between the oral and GI microbial communities.36,37 The bacteria that cause periodontitis exploit the link between oral and systemic health. This connection is facilitated by the circulation of inflammatory molecules and bacteria from the oral cavity to the GI system using saliva as a conduit.1 Once in the gut, dysbiotic oral bacteria disrupt the gut barrier function and alter the immune profile, leading to GI dysbiosis that, in turn, triggers endotoxemia and systemic inflammation, which is a hallmark of many chronic diseases.1

Education and Intervention

In light of these intricate connections between oral and systemic health, healthcare professionals, particularly dental healthcare professionals, have a pivotal role to play in educating patients about the significance of maintaining good oral health as it pertains to overall health. Regular dental check-ups and meticulous oral hygiene practices are essential not only to preserve the health of gingiva and teeth but also to mitigate inflammation and its systemic consequences.

Dental healthcare professionals can provide valuable guidance regarding dietary habits that support oral and gut health. A balanced diet rich in prebiotics, which nourish beneficial GI bacteria, and probiotics, which introduce beneficial bacteria into the GI system, can be advantageous.38 According to research, lipid pro-resolving mediators can have positive effects on oral symbiosis and the reversal of dysbiosis. Omega-3 fatty acids, such as ɑ-lineoic acid and eicosapentaenoic acid (EPA), have been shown to reverse microbiome dysbiosis in animal models, which could lead to promising therapies for those who struggle with maintaining eubiosis.39,40 These dietary interventions can indirectly foster a healthy GI microbiome that supports oral health. In addition, oral microbiota transplantation using plaque from a healthy donor, which was inspired by the success of fecal microbiota transplantation in improving GI health, has been suggested to address periodontitis and caries.41,42

Conclusion

The concept of the gum-gut connection illustrates the intricate interplay that occurs between the body's microbiomes and the profound influence that these relationships have on overall health. Recognizing the role of the oral microbiome in systemic health is of paramount importance for healthcare providers across all disciplines. Furthermore, the gum-gut connection underscores the necessity of adopting an integrated approach to patient care that acknowledges the interconnected nature of the body's microbial ecosystems and leverages a collaborative healthcare team in providing holistic treatment.

Queries regarding this course may be submitted to authorqueries@broadcastmed.com

About the Author

Steven R. Sheibley, DMD
PGY2 Periodontology Resident
University of Alabama at Birmingham
School of Dentistry
Birmingham, Alabama

Maria L. Geisinger, DDS, MS
Diplomate
American Board of Periodontology
Professor and Director
Advanced Education Program in Periodontology
University of Alabama at Birmingham
School of Dentistry
Birmingham, Alabama

References

1. Olsen I, Yamazaki K. Can oral bacteria affect the microbiome of the gut? J Oral Microbiol. 2019;11(1):1586422.

2. Kilian M, Chapple ILC, Hannig M, et al. The oral microbiome - an update for oral healthcare professionals. Br Dent J. 2016; 221(10):657-666.

3. Cho I, Blaser MJ. The human microbiome: at the interface of health and disease. Nat Rev Genet. 2012;13(4):260-270.

4. Wu J, Peters BA, Dominianni C, et al. Cigarette smoking and the oral microbiome in a large study of American adults. ISME J. 2016;10(10):2435-2446.

5. Sedghi L, DiMassa V, Harrington A, et al. The oral microbiome: role of key organisms and complex networks in oral health and disease. Periodontol 2000. 2021;87(1):107-131.

6. Nath S, Pulikkotil SJ, Weyrich L, et al. Effect of periodontal interventions on characteristics of the periodontal microbial profile: a systemic review and meta-analysis. Microorganisms. 2022;10(8):1582.

7. Al-Rashidi HE. Gut microbiota and immunity relevance in eubiosis and dysbiosis. Saudi J Biol Sci. 2022;29(3):1628-1643.

8. Ribeiro AA, Jiao Y, Girnary M, et al. Oral biofilm dysbiosis during experimental periodontitis. Mol Oral Microbiol. 2022;37(6):256-265.

9. Hajishengallis G. Periodontitis: from microbial immune subversion to systemic inflammation. Nat Rev Immunol. 2015;15(1):30-44.

10. Socransky SS, Haffajee AD, Cugini MA, et al. Microbial complexes in subgingival plaque. J Clin Periodontol. 1998;25(2):134-144.

11. Costalonga M, Herzberg MC. The oral microbiome and the immunobiology of periodontal disease and caries. Immunol Lett. 2014;162(2 Pt A):22-38.

12. Edgar WM, O'Mullane DM, Dawes C. Saliva and Oral Health. 3rd ed. London: British Dental Association; 2004.

13. Marsh PD, Do T, Beighton D, Devine DA. Influence of saliva on the oral microbiota. Periodontol 2000. 2016;70:80-92.

14. Walker MY, Pratap S, Southerland JH, et al. Role of oral and gut microbiome in nitric oxide-mediated colon motility. Nitric Oxide. 2018;73:81-88.

15. Li YH, Tian X. Quorum sensing and bacterial social interactions in biofilms. Sensors (Basel). 2012;12(3):2519-2538.

16. Han YW, Wang X. Mobile microbiome: oral bacteria in extra-oral infections and inflammation. J Dent Res. 2013;92(6):485-491.

17. Wagner C, Zimmermann S, Brenner-Weiss G, et al. The quorum-sensing molecule N-3-oxododecanoyl homoserine lactone (3OC12-HSL) enhances the host defence by activating human polymorphonuclear neutrophils (PMN). Anal Bioanal Chem. 2007;387(2):481-487.

18. Hajishengallis G, Lamont RJ. Breaking bad: manipulation of the host response by Porphyromonas gingivalis. Eur J Immunol. 2014;44(2):328-338.

19. Hajishengallis G, Lamont RJ. Polymicrobial communities in periodontal disease: their quasi-organismal nature and dialogue with the host. Periodontol 2000. 2021;86(1):210-230.

20. Zhang JS, Chu CH, Yu OY. Oral microbiome and dental caries development. Dent J (Basel). 2022;10(10):184.

21. Hajishengallis G. Immunomicrobial pathogenesis of periodontitis: keystones, pathobionts, and host response. Trends Immunol. 2014;35(1):3-11.

22. American Academy of Periodontology. Glossary of periodontal terms: periodontitis. AAP Connect website. https://members.perio.org/libraries/ glossary/entry?GlossaryKey=d93c420e-9322-4bdd-b01c-d545af310a5b. Updated October 6, 2012. Accessed February 5, 2024.

23. Hajishengallis G, Lamont RJ. Beyond the red complex and into more complexity: the polymicrobial synergy and dysbiosis (PSD) model of periodontal disease etiology. Mol Oral Microbiol. 2012;27(6):409-419.

24. Chapple ILC, Matthews JB. The role of reactive oxygen and antioxidant species in periodontal tissue destruction. Periodontol 2000. 2007;43:160-232.

25. Chapple ILC, Genco R. Diabetes and periodontal diseases: consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J Clin Periodontol. 2013;40(Suppl 14):S106-S112.

26. Genco RJ, Van Dyke TE. Prevention: reducing the risk of CVD in patients with periodontitis. Nat Rev Cardiol. 2010;7(9):479-480.

27. Krajmalnik-Brown R, Ilhan ZE, Kang DW, DiBaise JK. Effects of gut microbes on nutrient absorption and energy regulation. Nutr Clin Pract. 2012;27(2):201-214.

28. Fukuda S, Ohno H. Gut microbiome and metabolic diseases. Semin Immunopathol. 2014;36(1):103-114.

29. Byrd KM, Gulati AS. The "gum-gut" axis in inflammatory bowel diseases: a hypothesis-driven review of associations and advances. Front Immunol. 2021;12:620124.

30. Olsen I, Yilmaz Ö. Possible role of Porphyromonas gingivalis in orodigestive cancers. J Oral Microbiol. 2019;11(1):1563410.

31. Zenobia C, Hajishengallis G. Porphyromonas gingivalis virulence factors involved in subversion of leukocytes and microbial dysbiosis. Virulence. 2015;6(3):236-243.

32. Arimatsu K, Yamada H, Miyazawa H, et al. Oral pathobiont induces systemic inflammation and metabolic changes associated with alteration of gut microbiota. Sci Rep. 2014;4:4828.

33. Chen Q, Zhang Z, Bei S, et al. Efficacy of oral fecal microbiota transplantation in recurrent bowel disease: a protocol for systematic review and meta-analysis. Medicine (Baltimore). 2022;101(47):e31477.

34. Ser HL, Letchumanan V, Goh BH, et al. The use of fecal microbiome transplant in treating human diseases: too early for poop? Front Microbiol. 2021;12:519836.

35. Darveau RP. Periodontitis: a polymicrobial disruption of host homeostasis. Nat Rev Microbiol. 2010;8(7):481-490.

36. Hajishengallis G, Liang S, Payne MA, et al. Low-abundance biofilm species orchestrates inflammatory periodontal disease through the commensal microbiota and complement. Cell Host Microbe. 2011;10(5):497-506.

37. Madianos PN, Bobetsis YA, Offenbacher S. Adverse pregnancy outcomes (APOs) and periodontal disease: pathogenic mechanisms. J Clin Periodontol. 2013;40(Suppl 14):S170-S180.

38. de Oliveira AM, Lourenço TGB, Colombo APV. Impact of systemic probiotics as adjuncts to subgingival instrumentation on the oral-gut microbiota associated with periodontitis: a randomized controlled clinical trial. J Periodontol. 2022;93(1):31-44.

39. Van Dyke TE. Pro-resolving mediators in the regulation of periodontal disease. Mol Aspects Med. 2017;58:21-36.

40. Martínez-García M, Hernández-Lemus E. Periodontal inflammation and systemic diseases: an overview. Front Physiol. 2021;12:709438.

41. Nascimento MM. Oral microbiota transplant: a potential new therapy for oral diseases. J Calif Dent Assoc. 2017;45(10):565-568.

42. Pozhitkov AE, Leroux BG, Randolph TW, et al. Towards microbiome transplant as a therapy for periodontitis: an exploratory study of periodontitis microbial signature contrasted by oral health, caries, and edentulism. BMC Oral Health. 2015;15:125.

(1.) Examples of conditions that can occur when dysbiotic bacteria associated with periodontitis disrupt the GI microbiome via salivary transfer and lead to systemic disruptions through generalized inflammation.

Figure 1

Take the Accredited CE Quiz:

CREDITS: 2 SI
COST: $16.00
PROVIDER: AEGIS Publications, LLC
SOURCE: Inside Dentistry | April 2024

Learning Objectives:

  • Describe the oral microbiome and its effect on oral diseases, including caries and periodontitis.
  • Evaluate the GI microbiome and its effect on systemic diseases.
  • Discuss the implications of the gum-gut connection and explain some of its mechanisms.
  • Summarize the importance of patient education about the gum-gut connection and identify some interventions that can help to reverse dysbiosis and mitigate inflammation.

Disclosures:

The author reports no conflicts of interest associated with this work.

Queries for the author may be directed to justin.romano@broadcastmed.com.