Pathophysiology of oral cavity diseases. Textbook

The role of periodontal diseases as a risk factor in the development and/or progression of systemic conditions such as diabetes mellitus, rheumatoid arthritis, cardiovascular diseases, adverse pregnancy outcomes, and head and neck cancers has been the subject of extensive research in recent years.

Three primary mechanisms linking oral infections with systemic pathology have been revealed:

– The spread of infection from the oral cavity due to transient bacteremia,

– The circulation of microbial toxins,

– Systemic inflammation triggered by adverse immune responses to oral microorganisms.

CONCEPT OF BIOFILM

Periodontal diseases share many associative and cause-and-effect relationships with systemic diseases and may increase susceptibility to them through common risk factors, such as the presence of pathogenic Gram-negative anaerobic microorganisms in subgingival biofilms and the transformation of the periodontium into a reservoir for inflammatory mediators.

Under natural conditions, microorganisms can exist either as planktonic (free-floating) cultures or as biofilms. For the past 100 years, research activity has primarily focused on planktonic bacterial cultures; however, it is now widely recognized that microorganisms in the oral cavity are organized in the form of biofilms.

BIOFILM FORMATION

A biofilm is an accumulation of bacteria that exist as closely connected communities, adhering to various types of surfaces (both natural and artificial), typically in an aquatic environment containing sufficient concentrations of nutrients necessary to support the metabolic needs of the microbiota (Listgarten MA, 1999). Based on this definition, we can note that dental plaque has common characteristics with a biofilm. The oropharynx is an open ecosystem where bacteria are constantly present, seeking to colonize all favorable areas. Preferred targets for bacterial colonization include the hard and soft palate, subgingival and supragingival surfaces, teeth, lips, cheeks, and tonsils. Most bacteria can persist after biofilm formation on non-shedding surfaces, i.e., hard tissues (tooth and root surfaces, restorative materials, implants, dentures, etc.).

In conditions of healthy dental and gingival relationships, there is a balance between the additive and retention mechanisms of biofilms on the one hand, and the abrasive forces that tend to reduce biofilm formation (e.g., self-cleaning by the cheeks and tongue, dietary habits, and mechanical oral hygiene practices) on the other. Disruption of this ecosystem balance (due to its overload or weakening of immune mechanisms) may become a problem not only at the local level but also systemically. Therefore, the gold standard in the prevention of diseases associated with the pathogenic impact of microorganisms is the direct removal of biofilms from teeth, restorations, or dentures through regular tooth brushing.

Biofilm formation

Within minutes after thorough cleaning the tooth surface, a thin film (pellicle) forms. It is composed of proteins and glycoproteins found in saliva. The subsequent formation of the biofilm (dental plaque) occurs as follows:

– Association (Binding): Due to purely physical forces, bacteria freely bind to the thin pellicle.

– Adhesion (Sticking): Individual bacteria, having special surface molecules (adhesins), attach to receptors on the tooth surface. These bacteria are called «primary colonizers,» with examples including Streptococci and Actinomyces. Subsequently, other microorganisms join these primary colonizers.

– Bacterial Proliferation: Once attached, the bacteria begin to actively proliferate, increasing the bacterial population in the biofilm.

– Formation of Microcolonies: Over time, the bacteria aggregate into microcolonies. Many Streptococci secrete protective polysaccharides that help them solidify their attachment.

– Biofilm Formation: These microcolonies become a part of a complex structure known as a biofilm or «attached dental plaque.» Within this structure, bacteria gain metabolic advantages.

– Growth and Maturation of Dental Plaque: The dental plaque starts to function as a complex system with its own primitive «circulatory system.» As the plaque matures, the number of anaerobic bacteria increases. Metabolic byproducts and cell wall components causes a response from the human immune system. Due to the biofilm structure, the bacteria inside it are protected from phagocytic cells and external bactericidal agents.

FACTORS INFLUENCING THE FORMATION OF MICROFLORA

The formation of the oral microflora is influenced by numerous factors that contribute to the selection of microorganisms and the maintenance of balance among bacterial populations. These factors are as follows:

– The condition and structural features of the oral mucosa

– Temperature and pH of the oral cavity

– Salivation

– Condition of the teeth

– Diet composition

– Oral hygiene

– The natural resistance of the body

The oral microflora consists of a wide range of microorganisms. Some of these microorganisms are permanently present in the oral cavity and are called autochthonous microflora, while others, known as allochthonous microflora, originate from other parts of the body. The autochthonous microflora is further divided into resident (permanent) and transient (temporary) species. Resident flora consists of relatively stable bacterial species specific to a given biotope and the age of the host organism, and it quickly recovers after disturbances. Transient flora colonizes the oral cavity for a short period of time and, since it includes not only non-pathogenic but also opportunistic microorganisms, it can cause some diseases if the balance with resident flora is disordered. Allochthonous microflora includes microbes that are typically found in other parts of the body, such as the intestines and nasopharynx.

THE ROLE OF ORAL MICROFLORA

The normal microflora of the oral cavity plays a critical role in human health:

– Stimulates the development of lymphoid tissue.

– Inhibits the proliferation of pathogenic bacteria through competition for resources, alteration of the environmental acidity, and synthesis of substances with damaging effects, such as alcohols and hydrogen peroxide. For example, Lactococcus lactis, a bacterium that is a part of the normal microflora, can produce nisin, a bacteriocin that prevents tumor formation in the oral cavity and increases the lifespan of tumor-bearing mice.

– Maintains a healthy level of inflammation in the mucosa and helps the immune system to respond to various threats by providing a balance between inflammatory and anti-inflammatory processes.

– Facilitates self-cleaning of the oral cavity.

– Provides the body with essential amino acids and vitamins released by microorganisms during their metabolism. The oral microbiome also participates in the systemic circulation of nutrients, particularly through nitrate metabolism. Nearly 25% of ingested nitrates are transported via the enterosalivary circuit to the oral cavity, where oral microbes convert nitrate into nitrite, which enters the bloodstream during digestion and is converted into nitric oxide. Nitric oxide is important for cardiovascular health, as it has vasodilatory and hypotensive effects. Thus, the normal oral microflora is essential not only for maintaining oral health but also for supporting systemic health.

– Stimulates the secretion of salivary and mucous glands through the metabolic products produced by microorganisms.

IMMUNE MECHANISMS OF THE ORAL CAVITY

The oral cavity serves as a gateway to both the gastrointestinal and respiratory tracts, it consists of complex anatomical structures, and it is constantly exposed to antigens from the air and food. Various microorganisms colonize the environments provided by these structures. The rich community of symbiotic microbes and their metabolites, continuous tissue damage from chewing, antigens from food, and airborne particles present a potential problem for the homeostasis of the oral mucosa. Consequently, the mucosal surface and its inherent immune system are necessary to protect the internal environment of the body. The association between the epithelium and the innate and adaptive immune mechanisms is of the fundamental significance for the rapid recognition and effective elimination of pathogens on the epithelial surface. The mucosal immune system operates in two directions: preventing pathogen invasion and defending against foreign antigens, while simultaneously maintaining immunological tolerance toward symbiotic microorganisms and various harmless substances that contact the oral mucosa.

The oral cavity is an entry point for many microorganisms from the environment, therefore its protective functions are of paramount importance. The oral cavity hosts an active and complex immune defense system. The teeth and surrounding mucosa are continuously bathed in saliva, produced by both the major and minor salivary glands. Saliva is a watery fluid secreted by the salivary glands, containing numerous innate antimicrobial agents (immunoglobulins IgA, IgM, and IgG, as well as antimicrobial peptides like histatins, lysozyme, lactoferrin, peroxidases, and SLPI – secretory leukocyte protease inhibitor). It has been observed that patients with reduced saliva production have an increased susceptibility to oral candidiasis. In the area of the gingival crevice, which surrounds the crown of the tooth, gingival crevicular fluid is released. This fluid contains leukocytes, sIgA, complement system proteins, and other plasma components. As it penetrates the gingiva, it fills the gingival sulcus and flows along the teeth. During inflammation, the diffusion of gingival fluid accelerates.

Local Defense or Colonization Resistance

Local defense, also known as colonization resistance, is a complex protective system that has developed through evolution Its main task is the protection of mucous membranes being in direct contact with the external environment. The primary function of this system is to maintain the constancy of the internal environment of the body. Thus, the local immune system acts as the first line of defense against foreign substances and microorganisms.

The local immunity of the oral cavity has two main functions: the barrier-protective function and the protective function of saliva. In its turn, each of them is divided into non-specific and specific defense factors.

NON-SPECIFIC IMMUNE FACTORS

Non-specific protection of the oral cavity comprises a set of mechanical, chemical, and physiological processes that are independent of the recognition of the antigenic structure of incoming microbes.

Non-Specific Barrier Factors:

– Mucous membrane

– Normal microflora (colonization resistance)

– Leukocytes

– Desquamation of buccal epithelium