Oral Health Disorders: An Integrative Review of Dental Caries, Gingivitis, and Periodontitis

One of the most prevalent avoidable conditions that is known to be the main cause of oral discomfort and tooth loss is dental caries. It is a serious oral health condition that prevents people of all ages from achieving and maintaining good oral health [1]. Despite significant advancements in the oral health of the populace in a number of nations, the WHO noted that the worldwide issue of oral illness still exists. According to WHO, a number of oral diseases are linked to chronic illnesses, and poor oral health may have a significant impact on overall health and quality of life.

Four elements are needed for caries to develop: a) a susceptible host; b) cariogenic flora; c) a suitable substrate; and d) a sufficient amount of time. Increasing the host's resistance, reducing the quantity of microorganisms in touch with the tooth, altering the substrate by choosing non-cariogenic meals, and cutting down on the amount of time the substrate is in the mouth are some of the methods used to prevent caries. Vaccines are created and directed against the antigenic components of the primary causative agent, S. mutans, by comprehending the immunology of dental caries. Therefore, dental cavities will be avoided [3].

Dentistry began around 5000 B.C., when dental caries was thought to be caused by "tooth worms." The Latin word "caries," which means decay, is where the term "dental caries" first appeared in literature about 1634. At first, the phrase was used to refer to tooth holes. According to reports, one of the most prevalent and ancient diseases in humans is dental caries. Dental caries is a common chronic infectious illness caused by cariogenic bacteria that cling to teeth and break down sugars to form acid, which eventually demineralizes tooth structure.

A large part of any dentist's daily work involves treating dental caries lesions. Healthy teeth and oral health care are crucial for individuals from all walks of life. Over the course of a person's life, success and productivity are impacted by dental caries' impacts on growth and physical, emotional, and cognitive development [4,5] Dental caries was shown to be highly prevalent across all age groups in India, according to numerous epidemiological studies conducted in various regions of the country [6].

When cariogenic bacteria and dietary sources of sucrose or refined sugar colonise a susceptible tooth surface, tooth decay results. Bacteria that ferment carbohydrates produce lactic acid, which dissolves the tooth's hydroxyapatite crystal structure and causes caries [7,8]. People's daily lives are greatly impacted by discomfort, difficulties eating, chewing, smiling, and communicating as a result of missing, discoloured, or spoilt teeth [9]. Due to the rise in bacterial isolates resistant to the previous antibiotics in prescription practices, dentists and other dental professionals have recently changed their focus from prescribing narrow-spectrum antibiotics to broad-spectrum aminopenicillins [8,10,11]. While there are many different kinds of dental diseases, we mostly concentrate on periodontal disease, gingivitis, and tooth decay.

Periodontal disease: Bacterial colonisation causes Parkinson's disease (PD), a chronic inflammatory condition that damages the hard and soft tissues supporting teeth [12]. An increase in teeth brushing frequency lowers the concentration of systemic inflammatory marker levels in blood; hence, oral hygiene is a potential way to change the stroke risk. Poor oral hygiene is a contributing factor to both Parkinson's disease and caries [13]. In the early stages of the disease, periodontal disorders are thought to be asymptomatic, ranging from mildly inflamed gums and bleeding upon probing. However, as the disease progresses, it can become more severe, leading to pocket formation, bone loss, and looseness. At this point, it may be difficult to save, so time is crucial and informative [14,15]. As a result, there are four phases to the disease's severity and management complexity:                                                                           

Stage I: Initial Periodontitis.

Stage II: Moderate Periodontitis.

Stage III: Severe periodontitis that may result in more tooth loss.

Stage IV: Severe periodontitis that may result in dental loss

Gingivitis: A bacterial infection is the most prevalent cause of gingivitis, an inflammatory disease of the gums or gingival tissue. It is gingival inflammation without loss of attachment, meaning that the connective tissue's attachment to the tooth is still intact. Only the connective tissue and gingival epithelium's soft tissue are affected [16]. The symptoms of gingivitis include redness and puffiness in the afflicted area as well as bleeding when probed. It is linked to an inflammatory response to pro-inflammatory cytokines, which are known to balance humoral and cell-mediated immune responses [17]. Plaque-induced gingivitis, infectious gingivitis, nutritional gingivitis, hormonal gingivitis, and drug-induced gingivitis are the five forms of gingivitis.

Tooth decay: Dental caries, also referred to as cavities or tooth decay, is a widespread oral health problem that affects people of all ages worldwide. Due to its prevalence and possible effects on general health and quality of life, dental disease continues to be a major public health concern despite breakthroughs in dental care [18]. Microbial activity, host vulnerability, dietary habits, oral hygiene practices, and socioeconomic factors are only a few of the many variables that interact intricately during the illness process. All ages are affected by dental caries; however, children, teenagers, and older adults are more likely to have it. Untreated caries can have negative effects on general health and quality of life in addition to dental health [19].

2. HISTORY OF DENTAL DISEASES

Pre-agricultural societies had low rates of dental decay, but the emergence of farming society approximately 10,000 years ago was associated with a rise in cavities [20].  An infected tooth from Italy partially cleaned with flint tools, between 13,820 and 14,160 years old, represents the oldest known dentistry[21],  although a 2017 study suggests that 130,000 years ago the Neanderthals already used rudimentary dentistry tools[22,23]. Dental caries is attributed to a "tooth worm" according to an ancient Sumerian literature [24]. Ancient Egypt, China, Japan, and India have all shown evidence of this idea. The Homeric Hymns also contain references to the worm fable [25], and the surgeon Guy de Chauliac continued to propagate the idea that worms cause tooth decay as late as the 14th century AD [26].

Hippocrates and Aristotle, two ancient Greek philosophers, wrote on dentistry, including how teeth erupt, how to cure gum disease and decay, how to retrieve teeth with forceps, and how to stabilise loose teeth and cracked jaws using wires [27]. As early as 700 BC, the Etruscans in northern Italy used dentures, bridges, and dental appliances made of human or animal teeth joined by gold bands [28,29,30]. By the fifth century BC, the Romans had probably adopted this method. [29,31] In the sixth and fourth centuries BC, the Phoenicians made dentures using gold wire and two ivory teeth [32]. Hesy-Ra was the first "dentist" (greatest of the teeth) in ancient Egypt. The Egyptians used gold wire to bind substitute teeth together. Cornelius Celsus, a Roman physician, wrote a great deal on oral disorders and dental remedies such emollients and astringents that include narcotics.[33] Dental amalgams first emerged in Germany in 1528 and were first recorded in a Tang period medical literature written by the Chinese physician Su Kung in 659. [34,35]. Focal infection theory, which postulated that teeth with infected necrotic pulps and endodontically treated teeth might leak bacteria or their toxins into the body, causing arthritis and diseases of the kidney, heart, nervous system, gastrointestinal tract, endocrine system, and other systems, led to a terrifying period of tooth extraction for both the treatment of systemic diseases and as a preventative measure against future illness, in the early 1900s. Fortunately, further epidemiological and microbiological research refuted the notion that tooth extraction may improve the health of a person with a systemic illness. The tide of extraction was stemme [36].

3. PATHOPHYSIOLOGY OF PERIODONTAL DISEASE

Key bacteria in the dental biofilm are responsible for the onset and development of periodontitis. These bacteria trigger an inflammatory immune response that damages tissue in those who are vulnerable. In fact, it is well recognised that the host's immune-inflammatory reactions and the pathogenic subgingival biofilm interact intricately to cause periodontal disease. More than 700 different types of bacteria have been found in the subgingival microbiota [37]. Only a few bacteria, including the major periopathogens Fusobacterium nucleatum, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Aggregatibacter actinomycetemcomitans, are thought to be closely linked to the development of periodontitis [38]. The sulcular and junctional epithelium (JE) is the initial physical barrier that separates the microorganisms of the dental biofilm from the underlying mucosal connective tissue (CT). The development of periodontitis depends on both the presence of host risk factors and the transition to a dysbiotic biofilm. For example, an abnormal immunological response, including poor chemotaxis or excessive generation of reactive oxygen species by polymorphonuclear leukocytes (PMN), The periodontium experiences a series of tissue-damaging events when the dysbiotic biofilm is present [39]. Additionally, the body reacts to the biofilm's apical advancement by causing the JE to migrate apically, creating periodontal pockets. Gram-negative anaerobes dominate the subgingival microbiome, which becomes more complex and diverse as periodontal pocket depth increases. A number of powerful virulence factors, such as fimbriae and lectin-type adhesins, a polysaccharide capsule, LPS, hemagglutinins, potent proteinases, toxic metabolic products, outer membrane vesicles, and numerous enzymes, are also produced by important periodontal pathogens. These factors cause and sustain a strong immune response that results in the release of inflammatory mediators from the pocket epithelium [40]. In addition to receptor activator of nuclear factor-kappa B ligand (RANKL) stimulation, the host's increased expression of MMPs and prostaglandin E2 contributes to deepening the pocket and promoting alveolar bone resorption [41,42]. RANKL and its antagonist osteoprotegerin (OPG) are responsible for bone remodelling under normal physiological conditions [43]. Periodontitis disrupts the RANKL/OPG system because RANKL levels are significantly elevated, overwhelming OPG's decoy function and tipping the scales in favour of greater osteolytic activity [44]. It's interesting to note that RANKL can cause EMT by enhancing the nuclear translocation of EMT-associated transcription factors including Snail and Twist [45] and activating the NF-κB signalling pathway [45,46]. Neutrophils are found in relatively small numbers in the healthy periodontium, but once the bacterial infection triggers the host's pro-inflammatory response, neutrophils are recruited in relatively large numbers and release oxygen radicals and enzymes that work to lower the bacterial load. Periodontal disease is said to cause an increased neutrophilic response, and the molecules that are meant to eradicate bacteria can cause local tissue damage, which exacerbates the immune response and leads to a persistent inflammatory lesion that does not go away [47].

Inflammatory cell recruitment is a hallmark of the host's early and initial reaction to the dysbiotic subgingival biofilm within the periodontal pocket [48]. The inflammatory cytokine milieu, which is richer in cytokines including TNF-α, IL-1, IL-4, IL-10, interferon-γ, and TGF-β, is also influenced by the expanding immune cell populations at later stages of the disease [49]. Furthermore, RANKL, which promotes bone absorption and disintegration, is produced by CD4+T-cells [50].
As a result, the loss of epithelial integrity creates a pathway for periodontal bacteria to enter the underlying CT, where important fibroblast populations contribute to the defence system by releasing more inflammatory cytokines. Furthermore, in order to prevent periodontal bacteria from invading deeper tissues, they create a fibrous extracellular matrix (ECM) that walls off the inflammatory region [51,52] Under disease conditions, gingival fibroblasts can also secrete more proteolytic enzymes and pro-inflammatory proteins, including as prostaglandin E2 and MMP-2 [53], which aid in the resorption of bone and the destruction of soft tissue. Therefore, there are factors in this inflammatory environment that could lead to the local drive of EMT.

1. 1. PATHOPHYSIOLOGY OF GINGIVITIS

Periodontitis has been identified as the advanced stage of gingivitis, which has been classified pathophysiological into initial, early, and established phases.

1. Initial lesion: Acute exudative inflammation, increased gingival fluid flow, and neutrophil migration from the subgingival plexus blood artery in the gingival connective tissue to the gingival sulcus are the hallmarks of this stage. Fibrin builds up in the vicinity of vessels due to a change in the matrix of the connective tissue. Four days after the start of plaque buildup, the first lesion appears. Collagenase and other enzymes released by neutrophils cause collagen to break down. At this stage, the inflammatory infiltrate occupies between 5% and 10% of the connective tissue [54].

2. Early lesion: Delayed hypersensitivity is consistent with the early lesion. It typically manifests one week following the start of plaque accumulation. The clinical symptoms of gingivitis, including as gingival bleeding and redness, begin to manifest at this point. Macrophages and lymphocytes make up 75% of the inflammatory cells in this lesion. There are also a few plasma cells visible. In addition to the inflammatory infiltration that takes up 5% to 15% of the gingival margin's connective tissue, the afflicted area experiences a 60% to 70% reduction in collagen Additionally, the gingival fluid flow and the number of leukocytes moving to the area continue to rise, and the local fibroblasts experience a number of pathological alterations. The junctional epithelium also has an increase in neutrophils and mononuclear cells. It is unknown how long the early lesion will last; it might last longer than anticipated [54].

3. Established lesion: In this stage, there is a surge in T and B lymphocytes, plasma cells, macrophages, and collagenolytic activity. However, B lymphocytes and plasma cells are the most common cells. At this point, a little gingival pocket with a pocket epithelium is formed. There is a lot of organisations in the lesion. It has been proposed that a decrease in T cells and an increase in B cells and plasma cells is correlated with the severity of gingivitis. There are two possible outcomes for an established lesion: either it stays stable for months or years, or it develops into a more severe lesion that seems to be connected to a shift in the microbial ecology or gingival infection. After successful periodontal therapy, which raises the quantity of bacteria linked to periodontal health and coincides with a decrease in plasma cells and lymphocytes, this stage might be reversed [54].

4. Advanced lesion: This phase is a prelude to periodontitis. Irreversible attachment loss is its defining feature. The supporting tissues of the teeth and adjacent structures, such as the gingiva, periodontal ligament, and alveolar bone, are impacted by the inflammatory changes and bacterial infection, which can cause tooth loss [55,56].

3.2.  PATHOPHYSIOLOGY OF TOOTH DECAY

Enamel: The direction of the enamel rods, the various triangular patterns between pit and fissure, and the development of smooth-surface caries all contribute to the demineralisation of enamel by caries [57]. The enamel develops a number of unique zones as it loses minerals, including the translucent zone, dark zones, body of the lesion, and surface zone [58]. A 1/2% loss of minerals corresponds with the translucent zone [59]. Enamel is slightly remineralised in the dark zone. The lesion's body has the most demineralisation and damage. Until the tooth structure is lost and a cavitation occurs, the surface zone stays largely mineralised [60].

Dentine: The advancing front, the zone of bacterial penetration, and the zone of destruction are the three distinct regions impacted by caries in dentine, ranging from the deepest layer to the enamel [57]. The advancing front is a region of acid-demineralized dentine devoid of microorganisms. The areas where bacteria invade and eventually break down dentin are known as the zones of bacterial penetration and destruction. Proteolytic enzymes have degraded the organic matrix, resulting in a more diverse bacterial population in the destruction zone [59].

Cementum: When gingival collapse results from periodontal disease or trauma, the incidence of cemental caries rises in older persons. It is a long-term illness that starts as a big, shallow lesion and gradually spreads to the cementum and dentin of the root, resulting in a persistent pulp infection [61].

Figure 1. Flowchart of pathogenesis of dental caries

Some common drugs that are used in the dental diseases

Drugs that are used in Periodontal disease

Drugs that are used in gingivitis disease

Drug that are used in the tooth decay