Oral Microbiome: A Review of Its Impact on Oral and Systemic Health

Abstract

Purpose of review: This review investigates the oral microbiome's composition, functions, influencing factors, connections to oral and systemic diseases, and personalized oral care strategies.

Recent findings: The oral microbiome is a complex ecosystem consisting of bacteria, fungi, archaea, and viruses that contribute to oral health. Various factors, such as diet, smoking, alcohol consumption, lifestyle choices, and medical conditions, can affect the balance of the oral microbiome and lead to dysbiosis, which can result in oral health issues like dental caries, gingivitis, periodontitis, oral candidiasis, and halitosis. Importantly, our review explores novel associations between the oral microbiome and systemic diseases including gastrointestinal, cardiovascular, endocrinal, and neurological conditions, autoimmune diseases, and cancer. We comprehensively review the efficacy of interventions like dental probiotics, xylitol, oral rinses, fluoride, essential oils, oil pulling, and peptides in promoting oral health by modulating the oral microbiome.

Summary: This review emphasizes the critical functions of the oral microbiota in dental and overall health, providing insights into the effects of microbial imbalances on various diseases. It underlines the significant connection between the oral microbiota and general health. Furthermore, it explores the advantages of probiotics and other dental care ingredients in promoting oral health and addressing common oral issues, offering a comprehensive strategy for personalized oral care.

Keywords: dysbiosis; oral care; oral diseases; oral microbiome; oral microbiota; probiotics; systemic diseases.

Figure 1

Oral–Gut pathways to IBD and systemic diseases: Oral microbes such as Porphyromonas gingivalis can take two distinct routes to enter the body. The first is the hematogenous route (shown on the left), often associated with dental problems like tooth decay, periodontitis, gingivitis, oral thrush, and halitosis, which can further lead to systemic conditions such as CVD, neurological disorders, autoimmune diseases, diabetes, IBD, and cancer. On the other hand, the enteral route (shown in the right) allows these oral microbes to travel from the stomach to the intestines. P. gingivalis, which possesses resistance to antibiotics and can survive stomach acid, moves from the stomach into the gut. Changes in gastric acidity can alter the gut microbiota, making it resemble the oral microbiome. Upon entering the gastrointestinal tract, P. gingivalis disrupts the intestinal barrier, compromising gut integrity. This disruption, along with changes in the microbiome, initiates inflammation, typically occurring in the ileum. Within this inflammatory response, specific immune cells known as IL9+ CD4+ lamina propria T cells become active and produce IL-9, a cytokine that fuels immune responses and inflammation. While inflammation serves as a defense against invaders, excessive or chronic inflammation can lead to conditions like IBD. Abbreviations: IL-9: Interleukin-9; IL9+ CD4+ lamina propria T cells: immune cells producing IL-9; IBD: inflammatory bowel disease.

Figure 2

Mechanisms of Candida albicans pathogenicity. (A) Adhesion to host surfaces: Candida albicans initially adheres to host surfaces through weak and reversible interactions influenced by hydrophobic and electrostatic forces, facilitated by host tissue receptor glycoproteins ALS and HWP1. (B) Phenotypic switch: C. albicans can phenotypically switch between yeast and hyphal states. (C) Host cell receptor interaction: C. albicans can adhere to epithelial cells using various host cell receptors, such as EphA2 (through β-glucan) and E-cadherin (through ALS3). Host cell transglutaminases create a cross-linking between C. albicans and the epithelial surface by interacting with HWP1. (D) Biofilm formation: Interaction with oral bacteria, such as Streptococcus gordonii, promotes the formation of biofilms. ALS3 on C. albicans binds to surface protein SspB on S. gordonii, facilitating biofilm formation. (E) Hyphal penetration into epithelial cells: The shift to the hyphal form is crucial for tissue invasion. Hyphae infiltrate and harm epithelial cells, causing inflammation and white patches in oral thrush. Abbreviations: ALS: agglutinin-like sequence; HWP1: hyphal wall protein; SspB: surface protein SspB; EphA2: Eph receptor A2.

Figure 3

Mechanisms linking oral pathogens to RA. Porphyromonas gingivalis and RA link: P. gingivalis possesses virulent factors, including the PPAD, which citrullinates host proteins. This citrullination is thought to trigger autoimmune responses, leading to the production of ACPAs characteristic of RA. NETs and ACPA production: NETs formed during periodontitis contribute to protein citrullination catalyzed by PAD4 enzymes, further enhancing ACPA production. Aggregatibacter actinomycetemcomitans and RA: A. actinomycetemcomitans secretes LtxA, triggering neutrophil hypercitrullination and the release of citrullinated autoantigens, further fueling the ACPA response. Citrullinated autoantigens can trigger an autoimmune response, wherein Th17 cells in the immune system become overactivated. Th17 cells are known for producing pro-inflammatory cytokines, notably IL-17. IL-17 stimulates B cells to produce antibodies, including ACPAs. These antibodies can target citrullinated proteins, contributing to the autoimmune processes and inflammation seen in RA. Abbreviations: PPAD: protein arginine deiminase of P. gingivalis; ACPAs: anticitrullinated protein antibodies; PAD4: peptidylarginine deiminase 4; LtxA: leukotoxin A; Th17: T helper 17; IL 17: interleukin-17; RA: rheumatoid arthritis.