Neelam Pandey1*, Shobha Bodduluri1, Steven Mathis1, Haribabu Bodduluri1, Ashwani Kumar2
1Department of Immunology and Microbiology, University of Louisville, Louisville, Kentucky, USA
2Department of Life Sciences Mody University of Science and Technology, Lakshmangarh, Rajasthan, India
*Correspondence author: Neelam Pandey, Department of Immunology and Microbiology, University of Louisville, Louisville, Kentucky, USA;
Email: [email protected]
Published Date: 28-06-2024
Copyright© 2024 by Pandey N, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
The oral microbiota, comprising a diverse array of microorganisms inhabiting the oral cavity, plays a crucial role in maintaining oral and systemic health. This review paper provides a comprehensive analysis of the intricate relationship between oral microbiota and human health, highlighting its pivotal role in the prevention and development of various diseases. Key topics covered include the composition and dynamics of oral microbiota, its interactions with the host immune system and its implications in the pathogenesis of oral diseases such as dental caries, periodontal diseases and oral cancer. Furthermore, the systemic effects of oral microbiota on conditions such as cardiovascular disease, diabetes and respiratory infections are discussed. Additionally, emerging research on the therapeutic potential of modulating oral microbiota through probiotics, prebiotics and other interventions is reviewed. This paper underscores the significance of understanding and maintaining oral microbial balance for health and disease prevention.
Keywords: Oral Microbiota; Oral Health; Disease; Dysbiosis; Immune System; Dental Caries; Periodontal Diseases; Oral Cancer; Systemic Health; Probiotics, Prebiotics
Introduction
The pathogenic processes of oral disorders are closely associated with oral pathogens, which include bacteria, fungi, viruses, archaea and protozoa. Gomez and Nelson, indicated that the diversity of a toddler’s oral microbiome increases when they encounter their first colonizing microorganisms [1]. Throughout an individual’s lifetime, the oral bacteria community and the host maintain a homeostatic balance via several bidirectional communication and regulatory mechanisms. Conversely, dental caries, periodontal disease and oral candidiasis may all result from dysbiosis of the oral microbiota [2].
Oral archaea, formerly thought to be limited to methanogens, have been found in samples of caries biofilm, subgingival biofilms and inflammatory pulp tissue, among other situations [3]. These findings suggest that archaea may be involved in the pathogenic processes behind oral diseases [4]. About 100 different types of fungi, such as Aspergillus, Aureobasidium, Candida, Cladosporium, Cryptococcus, Fusarium, Gibberella, Penicillium, Rhodotorula, Saccharomycetales and Schizophyllum, [5] are found in the oral cavity. Fungi have been found in supragingival plaque, dental rinses and specimens from the hard palate. They make up 0.004% of all oral microbes. A wide variety of fungi have been found in saliva samples recently and two distinct genus-level community types (Malassezia and Candida) have been found [6].
Phages and eukaryotic viruses make up the oral virome, with the Anelloviridae, Herpesviridae and Papillomaviridae families of viruses making up most of the eukaryotic viruses. More varied, phages have been investigated for their ability to cause bacterial lysis, an effect that may be used in the treatment of bacterial infectious illnesses. Numerous oral viruses continue to exist in research and may serve as hosts for harmful genes in the mouth environment [7].
Oral viruses are now gender-specific, individualized and persistent, with very comparable viral populations in similar contexts. It will need further research to determine their possible pathogenicity [8]. Lung infections are mostly caused by oral microbiota and airborne bacteria. By preserving a dynamic balance with the host’s immune-inflammatory response, oral microbiome symbiosis lowers the likelihood of oral microbiome infiltration in the lungs and respiratory system [9]. Oral microbiome dysbiosis is brought on by poor oral health, smoking, inadequate dental care, illnesses and drugs. Conversely, excellent respiratory health is linked to good oral health. Periodontitis, gingivitis, tooth loss and oral cancer are among the oral disorders that result from this dysbiosis, which also triggers the host’s immune-inflammatory response. Additionally, oral dysbiosis increases the inoculum of inflammatory and pathogenic bacteria, which leads to microbial penetration of the lungs and respiratory system [10]. Lung microbiome localization has been linked to lung cancer and respiratory conditions such as asthma, COPD, pneumonia and lung injury [11]. Because oral disorders are linked to respiratory difficulties, the connections between the lung and the oral microbiota are important in lung diseases. Lung and mouth disorders may be made worse by this vicious cycle of respiratory, oral and oral microbiota dysbiosis [12].
Composition of Oral Microbiota
Bacteria
Most oral microorganisms are bacteria and previous culture-dependent techniques have provided most of the information on their makeup. These techniques revealed certain microbes linked to periodontitis and dental cavities, but they understated the variety of the oral microbiome. Our knowledge of the richness and variety of the oral microbiome has increased with the introduction of culture-independent techniques, which specifically target 16S ribosomal RNA [13]. Ninety-four percent of the species found in the oral bacterial community belong to six main phyla: Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, Spirochaetes and Fusobacteria. Saccharibacteria, Synergistetes, SR1, Gracilibacteria, Chlamydia, Chloroflexi, Tenericutes and Chlorobi are the remaining phyla. Despite advancements, uncultivable microbial species still prevent the laboratory cultivation of a significant fraction of oral bacteria. These microbes have needs for life, such as precise pH and temperature, contact with other microbes in their community and access to certain nutrients [14].
Fungi
There are a lot of fungi in the mouth. Fungi aren’t only immune-compromised individuals’ opportunistic pathogens; they’re also part of a balanced oral microbiome. According to a thorough analysis of oral fungus, healthy individuals harbor up to 101 different fungal species. Additionally, it was noted that each person’s oral cavity had between nine and twenty-three different fungus species. The most common species were Candida, followed by Cladosporium, Aureobasidium, Saccharomyces, Aspergillus, Fusarium and Cryptococcus [15,16].
Archea
Only a small portion of the oral microbiome is made up of archaea, which are only found in a few species. Thermoplasmatales, Methanobrevibacter, Methanobacterium, Methanosarcina and Methanosphaera are the methanogen species that were discovered [17]. Although they may be seen in healthy patients, those with periodontitis have higher numbers and prevalence of them [18].
Viruses
Diseases are linked to most oral viruses. Mucocutaneous orofacial disease, recurring lesions on the face and lips and primary herpetic gingivostomatitis are all brought on by the herpes simplex virus [19]. Numerous lesions in the oral cavity are caused by the human papillomavirus, including oral condylomas, benign-like oral papillomas and localized epithelial hyperplasia shown in Fig. 1 [20]. Several oral symptoms, including oral candidiasis, oral hairy leukoplakia, necrotizing ulcerative periodontitis, linear gingival erythema and Kaposi’s sarcoma, may also be indirectly caused by HIV infection [21].
Figure 1: Factors influencing the diversity and abundance of oral microbiota, such as host genetics, oral hygiene practices, diet and environmental factors.
Factors Influencing the Diversity and Abundance of Oral Microbiota
Effects of Host Genetics on the Oral Microbiome
The composition and diversity of the oral microbiome are substantially influenced by host genetics. To examine the bacterial similarity between twin pairs and unrelated participants, ß-diversity studies utilizing weighted and unweighted UniFrac distances (quantify the dissimilarity or similarity between microbial communities) and Bray-Curtis metrics were carried out. The R program irr was used to compute the intraclass correlation and determine the similarity of microbial abundances between the MZ and DZ twin pairs. Variance component approaches employing Sequential Oligogenic Linkage Analysis Routines (SOLAR, version 6.6.2; West Foundation for Biomedical Research, San Antonio, TX, USA) [22] were used to calculate the heritability estimates of the oral microbiota. Using R software (version 3.1.2), bacterial abundances (normalized OTU counts) were normalized by inverse normal transformation after being fitted to a linear regression model and corrected for age, sex, MetS and the total amount of bacteria in each sample. The trait’s rank is matched to a quantile in a normal distribution using the inverse normal transformation technique [23].
Effects of Oral Hygiene Practices on the Oral Microbiome
Oral hygiene practices profoundly impact the composition and diversity of the oral microbiome. There is a substantial and complex relationship between oral hygiene habits and oral microbiota. The makeup and diversity of microbial communities in the oral cavity are significantly influenced by routine dental care, which includes chemical treatments such as mouth rinses and mechanical disruption of plaque by brushing and flossing. Maintaining good oral hygiene helps to reduce the growth of harmful germs, which in turn prevents dental illnesses like periodontitis and caries from developing and becoming worse. Additionally, it promotes the growth of helpful and commensal microorganisms, supporting a healthy oral habitat. On the other hand, noncompliance with recommended oral hygiene practices, including overuse of antibiotics or harsh brushing methods, may upset the balance of microorganisms, leading to dysbiosis and putting people at risk for oral health issues. Therefore, developing specialized preventative interventions to support oral health and microbial balance requires a thorough knowledge of the complex interactions between oral hygiene practices and the oral microbiome [24].
Effects of Diet on the Oral Microbiome
The content and function of the oral microbiome are significantly impacted by diet. Diets high in sugar encourage the growth of acidogenic organisms like Streptococcus mutans, which increases the risk of dental caries. On the other hand, diets high in fiber encourage the development of good bacteria, improving dental health and microbial variety. Fruits, vegetables and dairy products include micronutrients that influence microbial populations by directly affecting microbes and modulating host immunological responses. On the other hand, consuming acidic or highly processed meals regularly may upset the balance of microbes, leading to dysbiosis and increased vulnerability to oral health issues. For this reason, nutritional therapies that support a balanced, nutrient-rich diet are essential for both oral microbial equilibrium and general oral health [25].
Effects of Environmental Factors on the Oral Microbiome
These factors are significantly influenced by the host’s place of birth as well as the cultural setting in which they live. The environment around a person’s birthplace and cultural context may have a big impact on the variety and makeup of their oral microbiome. These factors come from a variety of places, including exposure to environmental microbes, nutrition, lifestyle choices and socioeconomic standing. Additionally, the dynamic interactions between the oral cavity’s microbial populations and the outside world may modify the makeup of these communities. Significantly, these factors are often thought to be hard to change and rather constant. Because these characteristics are diverse and multivariate, it is still difficult to target them with therapies, despite advancements in our knowledge of the oral microbiota and its interactions with environmental factors. Therefore, comprehensive methods that consider both individual and environmental variables may be necessary for initiatives aiming at changing various components of the oral microbiome.
Oral Microbiota and Health
The Symbiotic Relationship Between Oral Microbiota and Host Health
Oral and systemic health are dependent on the symbiotic link between the oral bacteria and host health. Commensal bacteria help with nutrition metabolism, pH regulation and the production of antimicrobial peptides, all of which promote dental health. Unbalances in the makeup of microorganisms or dysbiosis, may cause systemic illnesses like diabetes and cardiovascular disease as well as oral disorders like periodontitis and dental caries. It is essential to comprehend and manage this symbiotic interaction to create methods that effectively enhance oral health and avoid related systemic disorders [27].
Role of Oral Microbiota in Maintaining Oral Homeostasis
Through complex relationships with both the host and the oral microbial population, the oral microbiota is essential to preserving oral homeostasis. The mouth cavity is home to a wide variety of microorganisms, most of which are bacteria, which maintain this dynamic balance. Together, these microbial communities support oral health by their participation in vital processes including immune regulation, nutrition metabolism and biofilm production. Commensal bacteria have a preventive effect against oral illnesses by competing with prospective pathogens for resources and colonization sites. Furthermore, the oral microbiota influences inflammatory reactions and tissue healing processes by interacting with immune system components and host epithelial cells. Dental caries, periodontal diseases and abnormalities of the oral mucosa may result from dysbiosis. To maintain oral health and stop the development of illness, specific therapy techniques that consider the complex dynamics of the oral microbiota are essential [28].
Role of Oral Microbiota in Maintaining Saliva Production
The oral microbiota has a complex function in saliva production that is linked to several physiological processes that occur in the mouth cavity. Saliva production plays a vital role in maintaining oral homeostasis by aiding in digestion, lubrication, antibacterial defense and tooth remineralization. It is controlled by both neurological and hormonal systems [29]. Saliva production is influenced by oral bacteria in several ways. First, commensal bacteria help break down complex carbohydrates in food into simpler sugars that may trigger salivary flow via chemosensory and gustatory pathways. Furthermore, ammonia and short-chain fatty acids produced by microbial metabolism may indirectly affect the composition and function of salivary glands as well as the electrolyte content of saliva. Furthermore, oral bacteria and host epithelial cells interact to initiate signaling pathways that control salivary gland production. These complex regulatory systems may be upset by dysbiosis of the oral microbiota, which is defined by changes in the makeup and function of microorganisms. This can result in changes in the amount and quality of saliva. To clarify oral health and disease processes and create focused treatments geared at reestablishing oral equilibrium, it is essential to comprehend the interaction between oral bacteria and saliva production [30].
Role of Oral Microbiota in Maintaining pH Balance
The role of oral microbiota in maintaining pH balance is crucial for oral health and overall well-being. Through microbial metabolism and interactions with saliva, which serves as a buffer against acids generated during fermentation and promotes remineralization, the oral microbiota regulates the pH equilibrium of the mouth. While some commensal bacteria create alkali or ammonia to combat acidification, others produce acids like lactic acid, which adds to the acidity of plaque. Local pH is further regulated by oral bacterial biofilms. Dysbiosis may upset this equilibrium, resulting in tooth problems. Knowing this link is essential for developing oral health strategies because it highlights the importance of microbial balance-targeting therapies in the prevention of illnesses like periodontal disease and dental caries [31].
Oral Microbiota and Diseases
Dental Carries
Dental caries is one of the most common bacterial illnesses in humans, causing tooth deterioration and maybe even tooth loss. Because Streptococcus mutans generate lactic acid and can grow in low-pH environments, it has long been thought to be the etiological agent of caries. However, because S. mutans is not found in measurable amounts in 10-20% of caries patients, other acid-producing bacterial taxa must undoubtedly be at play. Molecular techniques including microarrays and the 16S rRNA approach Aas, et al., have shown that other species from the genera Atopobium, Propionibacterium and Lactobacillus were present at much greater levels in carious lesions with S. mutans. Low- pH non-S. mutans streptococci, Lactobacillus species and Bifidobacterium dentium were the most common in those participants with no detectable amounts of S. mutans. These findings led to the hypothesis that bacterial species other than S. mutans, such as thosefound in the genera Veillonella, Lactobacillus, Scardovia and Propionibacterium, as well as low-pH non-S. mutans streptococci, Actinomyces species and Atopobium species might be crucial in the development of caries. S. mutans and Streptococcus sobrinus were found to be colonized in the microbiomes of teenagers in Romania who had limited access to care, according to NGS analysis of the microbiomes of groups with low and high incidence of caries. On the other hand, the adolescents in Sweden who received excellent care were more commonly colonized by Actinomyces, Selenomonas, Prevotella and Capnocytophaga species than by S. mutans and S. sobrinus [32].
Rheumatoid Arthritis
There may be a connection between the oral microbiota and Rheumatoid Arthritis (RA), a chronic inflammatory illness that causes inflammation and damage to the joints. The pathophysiology of RA has been linked to dysbiosis of the oral microbiota, which is defined by changes in microbial composition and function [33]. Through a variety of pathways, some oral bacteria, most notably Porphyromonas gingivalis, have been linked to the start and progression of RA. Because of its distinct virulence components, P. gingivalis may elude the immune system of its host and encourage inflammation. Additionally, this bacterium can citrullinate host proteins, which produce citrullinated peptides that RA patients’ immune systems can identify. The idea that oral bacteria play a role in the etiology of RA is further supported by the discovery of citrullinated proteins in the periodontal tissues of patients suffering from periodontitis, a prevalent inflammatory oral disease linked to P. gingivalis infection [34]. Furthermore, immunological responses in vulnerable people may be triggered by the systemic spread of oral bacteria and their byproducts into the bloodstream, which might result in the onset or aggravation of RA.
Notwithstanding these correlations, further research is necessary to fully understand the specific processes behind the interaction between the oral microbiota and RA. By elucidating these pathways, one may be able to gain new insights into the genesis and treatment of RA and maybe open the door to creative therapeutic approaches that target the oral microbiota to slow the course of the illness and enhance patient outcomes [35].
Periodontitis Disease
Certain species of Treponema and Prevotella, Tannerella forsythia, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis are among the putative pathogens that have long been linked to periodontal disease. Yet, Socransky, et al., found that a complex of species, as opposed to a single etiologic agent, was a more appropriate way to identify oral illnesses via the use of checkerboard hybridization [36]. The most harmful of the five complexes identified by the authors was the “red complex.” According to Socransky, et al. and Socransky and Haffajee, this complex, which included P. gingivalis, T. forsythia and Treponema denticola, relied on the orange complex’s prior pockets of colonization. According to Socransky and Haffajee and Teles, et al., there is a substantial body of information on the species linked to periodontal disease [37]. Some research revealed the possibility of other red complex species connected to long-term periodontitis disease [38,39]. A comprehensive assessment of 1450 bacterial association studies of subgingival plaque were conducted recently and 41 of the studies were deemed suitable for analysis [40]. As a result of these investigations, they concluded that there were 17 other species or phylotypes linked to the illness; they are mentioned in Table 1 along with their Human Oral Taxon (HOT) classifications.
Bacterial taxa | Status (bacterial taxa are cultivable or classified as phylotypes) |
Anaeroglobus geminatus HOT 121 | Cultivable |
Archaea spp. | Cultivable |
Bacteroidales [G-2] sp. oral taxon 274 | Unnamed |
Desulfobulbus sp. oral taxon 041 | Phylotype |
Eubacterium [XI] [G- 5] saphenum HOT 759 | Cultivable |
Filifactor alocis HOT 539 | Cultivable |
Fretibacterium fastidious HOT 363 | Cultivable |
Fretibacterium sp. oral taxon 360 | Phylotype |
Fretibacterium sp. oral taxon 362 | Phylotype |
Mogibacterium timidum HOT 042 | Cultivable |
Peptostreptococcus stomatitis HOT 112 | Cultivable |
Porphyromonas endodontalis HOT 273 | Cultivable |
Selenomonas sputigena HOT 151 | Cultivable |
TM7 [G-5] sp. oral taxon 356 | Phylotype |
Treponema lecithinolyticum HOT 653 | Cultivable |
Treponema medium HOT 667 | Cultivable |
Treponema vincentii HOT 029 | Cultivable |
Table 1: Newly identified putative periodontal pathogens [40].
Oral Cancer
Oral cancer is a disease that comes from both host genetics and environmental factors; tobacco and alcohol intake, betel quid chewing and human papillomavirus infection are well-known risk factors. Oral Squamous Cell Carcinoma (OSCC), which is largely derived from the oral mucosa, is the illness [41]. Oral cancer is becoming more common and it is still a serious worldwide health issue. Additionally, only 15% of instances of oral cancer may be linked to the primary risk factors listed above, which means that other risk factors need to be investigated. Most of the tumor microenvironment may be made up of the many bacteria that cover every surface of the mouth cavity the so-called bacterial biofilm and the groups that live on the mucosal surface [42]. Numerous cancer forms have been linked to diverse microorganisms and alterations in distinct bacteria so far. Several early investigations using culture-based or molecular approaches have evaluated alterations in the oral microbiome related to cancer; however, a consensus has not been achieved because of the small number of strains/clones that are testable. On the other hand, the advent of NGS makes it possible to study microbial communities at a depth and coverage never before possible [43-47].
Cardiovascular Diseases
Oral dysbiosis is believed to be closely associated with systemic inflammation and periodontal disease. It has also been related to certain species, such as Porphyromonas gingivalis and Streptococcus mutans, which have been found to proliferate in conjunction with these conditions [48,49]. Oral dysbiosis and cardiovascular disease have also been linked to several other species, including Parvimonas micra, Eubacterium timidum, Eubacterium brachy and Eubacterium saphenum; Tannerella forsythia; E. denticola; Prevotella intermedia; Prevotella nigrescens; Actictinobacillus actinomycetemcomitan; Campylobacter rectus; and Eubacterium timidum, Eubacterium brachy and Eubacterium saphenum (Fig. 2) [50-52]. Researchers were unable to establish a causal link between oral dysbiosis and the prevalence of periodontal disease since most of these findings were produced after cross-sectional investigations [53]. Oral tissues experience immunological and inflammatory reactions brought on by the oral microbiota, which influences cardiometabolic health and accelerates the development of cardiovascular disease [54,55]. Additionally, aggravating systemic inflammation might be microbial bloodstream invasion and changes in gut microbiota brought on by oral gut microbiota transfer [56]. The last signs of oral dysbiosis include oxidative damage, thrombosis, immunoreaction and systemic inflammation. Because of the reciprocal nature of the interaction, systemic inflammation may potentially upset the oral microbiota’s equilibrium. The main goal of this research is to examine possible upstream causes of the pathological consequences that have been discussed previously [57-59].
Figure 2: The oral microbiota, influenced by various factors, affects cardiovascular health through systemic pathogen transfer, as shown in a figure correlating microorganisms with diseases and associated influencing factors.
Respiratory Diseases
The main causes of lung infections are oral microbiomes and airborne bacteria. The danger of oral microbiome infiltration in the respiratory system and lungs is decreased by oral microbiome symbiosis, which preserves the host’s dynamic balance with the immune- inflammatory response [60,61]. Both respiratory and dental health are positively correlated. Oral microbiome dysbiosis is brought on by certain food habits, smoking, illnesses, drugs and inadequate dental care. Such a dysbiosis triggers the host’s immune- inflammatory response and gives rise to several oral illnesses, including periodontitis, gingivitis, oral cancer and tooth loss. Additionally, oral dysbiosis raises the pathogenic and inflammatory microbe inoculum, which leads to microbial penetration of the lungs and respiratory system. As shown in Table 2, the microbiome’s location in the lung will lead to several respiratory conditions, such as pneumonia, asthma, COPD and lung cancer. Oral microbiome dysbiosis is the first step toward both oral and respiratory illnesses; on the other hand, oral and respiratory disorders exacerbate oral microbiome dysbiosis [62,63]. The lung-oral microbiota interactions in lung disorders have been succinctly outlined in a recent review study by Mammen, et al. In a similar vein, respiratory issues are linked to oral disorders and vice versa [64,65].
S No. | Oral Status | Pulmonary Status | Type of Study or Outcome | Involved Factors | Year Reference |
1 | – | Chronic lung diseases | Supragingival plaque of hospitalized patients with chronic lung diseases. Checkerboard DNA-DNA hybridization | Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacter cloacae | (2005) [67] |
2 | – | Respiratory infection | Denture plaque culture of 50 dependent elderly | Enterobacter cloaceae and Klebsiellla pneumonie | (2002) [68] |
3 | – | Lung inflammation | Acellular bronchial lavage Oral taxa analysis | Aspiration- derived microbiota | (2016) [69] |
Inflammatory cytokines and proinflammatory Th17 phenotype |
| ||||
4 | Compro mised oral health | – | Prospective nonrandomized study in ICU patients | Methicillin- resistant Staphylococcus aureus, Pseudomonas aeruginosa and ten genera of Gram-negative bacilli | (1992) [70] |
5 | Poor dental health | Hospital acquired pneumonia | Plaque index scores and quantitative cultures of dental plaques from ICU patients | Aerobic bacteria | (2004) [71] |
6 | – | Ventilator- associated pneumonia | Dental plaque and bronchoalveolar lavage sample from ICU patients undergoing mechanical ventilation | Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter species and enteric species | (2008) [72] |
7 | Oral care | Pneumonia | Oral health care Reduces risk of nosocomial pneumonia in elderly patient | – | (2002) [73] |
8 | Periodontitis | COPD | Cross-sectional study | Association Between periodontitis and COPD | (2018) [74] |
9 | Tooth loss Tooth decay Periodont itis. | Lung cancer | Nested case control study | – | (2019) [75] |
10 | Periodont itis | Asthma | A case control study analyzing periodontitis, oral microflora and asthma | Prevotella intermedia | (2020) [76] |
Table 2: Influence of oral health status and microbiome on respiratory diseases [66].
Unveiling the Role of Oral Microbiota in Inflammation and Immune Dysregulation
Inflammation
The oral microbiota is involved in the etiology of diseases, including inflammation, via complex pathways that include tissue injury, host immunological responses and microbial dysbiosis. Dysbiosis may upset the delicate balance between commensal and pathogenic bacteria in the oral cavity. Dysbiosis is defined by changes in microbial makeup and activity. Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans are two examples of pathogenic bacteria that have virulence characteristics that allow them to elude host immune monitoring and trigger inflammatory reactions. These bacteria may cause host cells to produce pro-inflammatory cytokines including Tumor Necrosis Factor- alpha (TNF-α), interleukin-1 beta (IL-1β) and Interleukin-6 (IL-6) by activating Toll-Like Receptors (TLRs) and other Pattern Recognition Receptors (PRRs). Furthermore, host tissues may be directly harmed and inflammation can be intensified by the release of bacterial toxins and enzymes such Lipopolysaccharide (LPS) and proteases. As shown in periodontal disorders, where chronic inflammation causes alveolar bone resorption and periodontal ligament disintegration, persistent inflammation in response to oral bacteria colonization may result in tissue damage. Furthermore, the bloodstream-borne spread of oral bacteria and their byproducts may exacerbate systemic inflammation and play a role in the etiology of several systemic illnesses, such as rheumatoid arthritis and cardiovascular disorders. To better understand disease causes and create targeted treatments aiming at regulating the oral microbiota to attenuate inflammation and enhance patient outcomes, it is essential to comprehend the intricate interaction between the oral microbiota and inflammatory processes [77].
Immune Dysregulations
Complex interactions between microbial components and human immunological responses control the oral microbiota’s contribution to disease pathogenesis, including immune dysregulation. Immune homeostasis may be disturbed by dysbiosis in the oral microbiota, which is characterized by changes in microbial function and composition. Some pathogenic bacteria, such Fusobacterium nucleatum and Porphyromonas gingivalis, have virulence factors that make it easier for them to manipulate immune responses and evade host immune monitoring. Through a variety of methods, including as disruption of Toll-Like Receptor (TLR) signaling, suppression of dendritic cell maturation and activation of regulatory T-cell (Treg) differentiation, these bacteria may influence host immune cells. Moreover, oral bacteria-derived substances that might aggravate immunological dysregulation include Lipopolysaccharide (LPS), peptidoglycan and extracellular vesicles. Prolonged activation of pro-inflammatory pathways after chronic exposure to various microbiological stimuli may result in tissue damage and the emergence of immune- mediated illnesses. Moreover, systemic autoimmune illnesses including systemic lupus erythematosus and rheumatoid arthritis may be partly caused by the systemic spread of oral bacteria and their byproducts into the circulation, which can trigger systemic immune responses. To unravel illness causes and create tailored therapy methods aiming at restoring immunological homeostasis and reducing disease development, it is essential to comprehend the intricate interaction between immune dysregulation and the oral microbiota [78].
Oral Microbiota Modulation
It is essential to strengthen oral defenses against pathogens and preserve the dynamic balance of the oral microecology because oral microorganisms play a significant role in the etiology and pathophysiology of systemic and oral disorders. Fighting oral diseases requires an understanding of the relationships between the microbial populations. If adhesion receptors are absent and appropriate partner bacteria are not present for metabolic cooperation, either in nutrition consumption or environmental control, a possible pathogen may be ruled out. Coexistence of a certain set of organisms increases their pathogenicity and raises the likelihood of systemic and oral disease development [79]. However, certain microbes, like P. gingivalis, which is considered a keystone pathogen, can modify the environment to influence how much of other microorganisms there are in an ecological niche [80].
Strategies for Maintaining a Healthy Oral Microbiota
Mechanical Debridement: The main goal of current treatment is to use mechanical techniques to reduce the number of harmful bacteria. The degree of plaque management may be raised by self-performed plaque removal techniques like tooth brushing [81]. Scaling, root planning and periodontal surgery are examples of professionally executed plaque removal procedures that may lower the quantity and makeup of harmful bacteria and restore the ecological balance of the oral microbiota. Following periodontal therapy, the germs linked to pockets deeper than 4 mm often decrease to very low or even undetectable levels. Following mechanical debridement, periodontal pathogens such as P. gingivalis, Tannerella forsythensis (T. forsythensis), T. denticola and Treponema socranskii were also significantly reduced in individuals with periodontitis. Nonetheless, there are obstacles and difficulties in eliminating plaque because of the intricate structure of the tooth and the restricted space available for operation. Because mechanical methods are non-specific, they also eliminate helpful microorganisms. More importantly, mechanical debridement hurts oral health in some ways because it dramatically reduces microbial richness and variety [82].
Antibiotics: Since surgical intervention and good oral hygiene practices are the most effective ways to treat oral disorders, the use of antibiotics in dentistry is restricted. Antibiotics are used to target certain harmful bacteria in humans and animals. Because local antibiotic treatment increases medication concentration in the crevicular fluid and reduces unwanted side effects in the system, it is recommended over systemic administration of antibiotics. When more severe illnesses or conventional treatment fails, they are used as an adjuvant to mechanical therapy for periodontitis. On the other hand, the makeup and number of different bacteria in the oral cavity change when manual therapies are coupled with systemic and local antibiotics. Research has shown that after cleaning and root planing, the amoxicillin/metronidazole group greatly improved periodontal parameters and decreased the levels of P. gingivalis, P. intermedia and T. forsythensis. However, empirical prescription based on clinical and bacteriological epidemiological criteria characterizes antibiotic usage in dental practice, which results in the ineffectiveness of regularly used antibiotics and the development of antimicrobial resistance un a variety of bacteria. Genomic investigation of the patient’s oral microbiome may be necessary for the effective use of antibiotics to identify the microorganisms that are present and ascertain how they respond to different treatments [83].
Probiotics and Prebiotics: Probiotics are living microorganisms that, when given in sufficient quantities, boost the host’s health. Their mechanisms of action include competing with potential pathogens for nutrients or adhesion sites, producing bacteriocins or other products that kill or inhibit pathogen growth, enhancing the integrity of the intestinal barrier, regulating cell proliferation and apoptosis and activating and modifying the mucosal immune system. Oral probiotics need to adhere to and infiltrate oral tissue, form a biofilm and not break down carbohydrates. Probiotic treatments for dental caries have been researched because they disrupt the growth of cariogenic microorganisms in the mouth. Probiotics are not, however, currently recommended for the treatment of dental caries due to inadequate data. It has been shown that probiotics work best in the treatment of oral disorders when combined with prebiotics, which are oligosaccharides that are poorly digested. They can suppress the development and activity of potentially harmful bacteria while promoting the growth and activity of good bacteria [84].
Explore the Potential of Emerging Therapies
Novel treatments such as phage therapy and microbial transplantation have great promise for correcting dysbiosis in the oral microbiome. To restore microbial balance, microbial transplantation entails moving healthy microbial communities from a donor to a recipient. This strategy might be used to mitigate disorders like tooth caries and periodontal diseases in the context of oral health by reintroducing beneficial bacteria and restoring a diversified and stable microbial population. On the other hand, phage treatment employs viruses called bacteriophages which infect and destroy certain bacteria as medicinal tools. Phage treatment provides an accurate and targeted approach to restore balance to the oral microbiota by eliminating harmful bacteria while protecting beneficial species. This strategy is a promising way to treat oral microbial imbalances and related disorders since it may reduce collateral harm to beneficial bacteria and reduce worries about antibiotic resistance.
Explore the Potential of Emerging Therapies
Novel treatments such as phage therapy and microbial transplantation have great promise for correcting dysbiosis in the oral microbiome. To restore microbial balance, microbial transplantation entails moving healthy microbial communities from a donor to a recipient. This strategy might be used to mitigate disorders like tooth caries and periodontal diseases in the context of oral health by reintroducing beneficial bacteria and restoring a diversified and stable microbial population. On the other hand, phage treatment employs viruses called bacteriophages which infect and destroy certain bacteria as medicinal tools. Phage treatment provides an accurate and targeted approach to restore balance to the oral microbiota by eliminating harmful bacteria while protecting beneficial species. This strategy is a promising way to treat oral microbial imbalances and related disorders since it may reduce collateral harm to beneficial bacteria and reduce worries about antibiotic resistance.
Challenges and Future Directions in Modulating Oral Microbiota for Health Promotion
The oral microbiota is complex and diverse, making it difficult to modify to promote health. A wide variety of microbial species may be found in the mouth cavity, where they create a dynamic ecosystem that is impacted by a variety of variables including exposure to the environment, genetic predispositions, dental hygiene habits and food. Because of its intricacy, it is difficult to modify the microbiota exactly without unintentionally upsetting its delicate equilibrium. Furthermore, preserving microbial variety is essential for good oral health since changes in the microbiota’s makeup may cause dysbiosis, which puts people at risk for several oral illnesses such as dental caries and periodontal disease. Comprehending the complex interplay between microbial interactions and the human immune system is essential to achieving targeted control of the oral microbiota while maintaining its variety and ecological balance. Through intricate interactions with the human immune system, the oral microbiota affects both innate immunity and acquired immunity. To discover microbial targets for intervention and to reduce any negative effects on host immunity, it is necessary to dissect the processes underlying these interactions to develop effective modulation techniques. Personalized precision medicine techniques in oral health therapies are crucial since it is essential to take individual differences in immune profiles and microbiota composition into account when customizing modulation approaches to populations [86].
Future developments in the field of oral health depend on using cutting-edge technologies such as metabolomics, metagenomics and meta transcriptomics. With these instruments, there are never-before-seen possibilities to learn more about the dynamics and purposes of the oral microbiota. Through dissecting the complicated relationships that exist between microbial populations and their surroundings, scientists may acquire crucial knowledge about how these complex ecosystems impact oral health and illness. Furthermore, individualized strategies that consider each person’s unique microbiota makeup and host response hold great potential for precision medicine. Clinicians may create tailored treatments that enhance oral microbiome balance and support long-term oral health outcomes by taking immunological profiles, lifestyle variables and genetic predispositions into account. Novel therapeutic approaches including phage treatment, microbial transplantation, probiotics and prebiotics provide intriguing new ways to precisely regulate the oral microbiota to improve health and reduce the risk of dysbiosis and related oral illnesses. By providing fresh methods for reestablishing microbial balance and function, these therapies have the potential to completely transform oral health care. To fully realize their potential, however, several obstacles must be removed, such as assuring effectiveness, safety and uniformity as well as comprehending their long-term impacts. Therefore, it is essential to conduct thorough research to overcome these obstacles and open the door for evidence-based solutions that maximize the benefits of focused alteration of the oral microbiota to preserve excellent oral health [87].
CRISPR-Cas Mediated Microbiome Engineering: A Promising Frontier for Oral Health Therapeutics
Novel approaches to microbiome engineering, especially those using CRISPR-Cas systems, provide encouraging prospects for medicinal modification of the oral microbiota. The intricate ecology of bacteria, fungi and viruses known as the oral microbiome has a major impact on both oral health and illness. This microbial community’s dysbiosis has been linked to several oral illnesses, such as periodontal disorders, dental caries and oral cancer. Researchers can accurately target and edit the genomes of microorganisms by using CRISPR-Cas systems, which provides them with unparalleled control over microbial populations. One tactic is to selectively alter harmful species-like Streptococcus mutans-by mutating genes related to virulence or antibiotic resistance, which lessens the toxicity of the species. On the other hand, if you want to increase the number or activity of good bacteria, such the probiotic Streptococcus salivarius, you may use CRISPR-Cas systems. CRISPR-mediated synthesis of synthetic microbial communities provides an additional strategy for reestablishing microbial balance in dysbiotic oral microbiomes. Effective delivery of CRISPR components to target bacteria in the oral cavity continues to present challenges, which calls for the investigation of alternative delivery vehicles such as customized probiotics and nanoparticles. The development of microbiome engineering technologies for therapeutic reasons necessitates thorough safety studies because to ethical and safety concerns, such as the possibility of off-target effects and horizontal gene transfer. To sum up, microbiome engineering shows significant potential for modifying the oral microbiome to prevent and cure oral disorders while preserving mouth health and microbial balance. This is especially true when it comes to the precise manipulation made possible by CRISPR-Cas systems [88].
Functional Aspects of the Oral Microbiome
The oral microbiota has essential functional functions in preserving oral homeostasis and health. This intricate ecosystem, which consists of a wide variety of bacteria, fungi and viruses, interacts constantly with both the host and the outside world. The functional features of the oral microbiome have been clarified by recent research, which also emphasizes the role it plays in immune regulation, barrier function and digestion, among other physiological processes [89]. For example, commensal bacteria like Streptococcus species aid in the metabolism of carbohydrates, making it easier for food sugars to be broken down and maintaining the pH equilibrium in the mouth. Furthermore, certain oral microorganisms are essential for the growth and maturity of the immune system; they help recognize and eliminate pathogens while preserving immunological tolerance to commensal species. Furthermore, via competitive exclusion and the synthesis of antimicrobial chemicals, the oral microbiome functions as a barrier of defense against the colonization of harmful microbes. Oral disorders such as dental caries and periodontal diseases have been linked to dysbiosis in the oral microbiome, which is defined by changes in the makeup and function of microbes. Developing focused treatment approaches and clarifying illness causes need an understanding of the functional dynamics of the oral microbiome. The oral microbiome’s complex metabolic pathways and microbial interactions have been uncovered by recent metagenomic investigations, which has shed light on the microbiome’s functional complexity. Furthermore, the discovery of new microbial species and roles has been made possible by developments in high-throughput sequencing technology, which has increased our knowledge of the ecology of oral microbes. Taken together, these discoveries highlight how crucial it is to consider the functional components of the oral microbiome when discussing oral health and disease prevention [90].
Clinical Implications
An important factor in oral health is the oral microbiome, which affects the onset and course of conditions including periodontitis and dental caries. These oral illnesses are intimately associated with dysbiosis within this microbial community, which is defined by changes in microbial composition and function. The discovery of microbial biomarkers indicative of disease state and development is made easier by extensive investigation of the oral microbiome made possible by advanced molecular approaches such as metagenomics and meta transcriptomics. By using these strategies, medical professionals may more accurately diagnose illnesses, forecast how well treatments will work and track the course of diseases over time. Furthermore, therapies that attempt to alter the oral microbiota provide encouraging new directions in treatment. Probiotics, which are made up of good bacteria, may be used to balance the microbiota again and stop the spread of harmful organisms. Similarly, by specifically targeting pathogenic microorganisms, targeted antimicrobial medicines provide a useful way to manage oral infections. Furthermore, prebiotics may aid in promoting a healthy oral microbiome by providing nutrients that stimulate the development of beneficial microorganisms.
Emerging research indicates that the oral microbiota may have an effect on systemic health in addition to oral health. Numerous systemic illnesses, such as diabetes, rheumatoid arthritis and cardiovascular disease, have been linked to dysbiosis in the oral microbiome. Clinicians may identify patients who are susceptible to these systemic illnesses and take appropriate preventative action by examining the oral microbiota. Oral health care might transform if standard clinical practice incorporates microbiome analysis. Through individualized treatment plans based on patient microbiomes, medical professionals may maximize therapeutic benefits and reduce side effects. This tailored approach highlights the significant clinical significance of the oral microbiota and improves both dental health and general well-being [91].
Future Directions
The study of the oral microbiome has a lot of potential for the future, since research is being done to better comprehend its intricate dynamics and practical applications. Multi- omics techniques, which integrate genomes, metagenomics, metabolomics and transcriptomics, are examples of advanced technologies that will provide a thorough understanding of microbial communities and their involvement in oral health and illness. Our understanding of microbial diversity and its correlation with oral and systemic health outcomes will be improved via integrative analysis of large-scale datasets from varied populations. Additionally, the interpretation of complicated microbiome data will be made easier by the development of cutting-edge computational tools and machine learning algorithms, which will result in more precise illness prediction and individualized treatment plans. Furthermore, research into the function of the oral microbiome in systemic disorders will keep growing to identify new mechanisms explaining interactions between the microbiome and the host as well as the pathophysiology of disease. Microbiome-based therapies and precision probiotics are two examples of targeted treatments that try to modify the oral microbiome and provide hope for both disease prevention and therapy. Moreover, the incorporation of microbiome research into standard clinical practice will transform oral health care by allowing customized strategies based on unique microbial profiles. As these technologies are embraced by more people, ethical issues about microbiome research-such as data security and privacy will also become more important. To summaries, the investigation of the oral microbiome will prioritize the utilization of advanced technology and multidisciplinary methodologies to decipher its intricacies and capitalize on its capacity to enhance dental and overall health consequences [92].
Discussion
The discussion section of this review paper provides a comprehensive analysis of the intricate relationship between oral microbiota and human health highlighting its pivotal role in the prevention and development of various diseases. The pivotal role of oral microbiota in maintaining health and disease has been studied by many researchers. Such as Wade, et al., Zarco, et al., and Santacroce, et al., [93-95].
Wade, et al., studied the diversity of the oral microbiome, including bacteria, viruses, fungi, protozoa and archaea and its correlation with common oral diseases such as dental caries and periodontal diseases [93]. Zarco, et al., studied the significance of the personalized oral microbiome in maintaining health and its potential role in causing both oral and systemic diseases [94]. Santacroce, et al., studied the importance of oral microbiota for human health and explored how dysbiosis can contribute to oral and systemic diseases [95]. It also discussed strategies like oral hygiene, diet and probiotics to promote healthy oral microbiota and reduce health risks.
The findings of the current investigation are oral microorganisms, spanning bacteria, fungi, viruses and protozoa, intricately influence oral diseases like caries and periodontal disease. Similarly, Wade, et al., revealed that the human mouth harbors a diverse microbiome, with representatives from various microbial kingdoms [95]. While bacterial species are highly diverse and responsible for common oral diseases, archaea are limited to methanogens whereas Santacroce, et al., dysbiosis of the oral microbiota, triggered by factors like diet, poor oral hygiene and smoking, can lead to the development of oral diseases such as caries and periodontal disease, as well as systemic health implications [95].
Conclusion
In conclusion, there is a close relationship between oral health and disease processes and the complex ecology of oral microorganisms, which includes bacteria, viruses, fungus and protozoa. Several infectious disorders, including dental caries, periodontal disease and oral candidiasis, may be brought on by dysbiosis in the oral microbiota. Although bacteria predominate in the oral microbiome, fungi and viruses also have important roles to play. Microbial communities are shaped by host immunological responses, environmental conditions and dietary patterns. To effectively design targeted treatment approaches, it is essential to comprehend the intricate interactions that exist between oral microbiota and systemic illnesses such as respiratory and cardiovascular problems, immunological dysregulation and inflammation. Novel approaches to therapeutic modification, such as CRISPR-Cas mediated microbiome editing, have encouraging prospects. In order to fully understand the oral microbiota and realize its potential for enhancing oral and systemic health outcomes, future research orientations should prioritize the use of sophisticated molecular tools and multidisciplinary approaches, all the while making sure ethical issues are taken into account.
Conflict of Interests
The authors declare no conflicts of interest.
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Article Type
Review Article
Publication History
Received Date: 04-06-2024
Accepted Date: 20-06-2024
Published Date: 28-06-2024
Copyright© 2024 by Pandey N, et al. All rights reserved. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation: Pandey N, et al. Role of Oral Microbiota in Preserving Health and Disease Management. J Clin Immunol Microbiol. 2024;5(2):1-17.
Figure 1: Factors influencing the diversity and abundance of oral microbiota, such as host genetics, oral hygiene practices, diet and environmental factors.
Figure 2: The oral microbiota, influenced by various factors, affects cardiovascular health through systemic pathogen transfer, as shown in a figure correlating microorganisms with diseases and associated influencing factors.
Bacterial taxa | Status (bacterial taxa are cultivable or classified as phylotypes) |
Anaeroglobus geminatus HOT 121 | Cultivable |
Archaea spp. | Cultivable |
Bacteroidales [G-2] sp. oral taxon 274 | Unnamed |
Desulfobulbus sp. oral taxon 041 | Phylotype |
Eubacterium [XI] [G- 5] saphenum HOT 759 | Cultivable |
Filifactor alocis HOT 539 | Cultivable |
Fretibacterium fastidious HOT 363 | Cultivable |
Fretibacterium sp. oral taxon 360 | Phylotype |
Fretibacterium sp. oral taxon 362 | Phylotype |
Mogibacterium timidum HOT 042 | Cultivable |
Peptostreptococcus stomatitis HOT 112 | Cultivable |
Porphyromonas endodontalis HOT 273 | Cultivable |
Selenomonas sputigena HOT 151 | Cultivable |
TM7 [G-5] sp. oral taxon 356 | Phylotype |
Treponema lecithinolyticum HOT 653 | Cultivable |
Treponema medium HOT 667 | Cultivable |
Treponema vincentii HOT 029 | Cultivable |
Table 1: Newly identified putative periodontal pathogens [40].
S No. | Oral Status | Pulmonary Status | Type of Study or Outcome | Involved Factors | Year Reference |
1 | – | Chronic lung diseases | Supragingival plaque of hospitalized patients with chronic lung diseases. Checkerboard DNA-DNA hybridization | Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacter cloacae | (2005) [67] |
2 | – | Respiratory infection | Denture plaque culture of 50 dependent elderly | Enterobacter cloaceae and Klebsiellla pneumonie | (2002) [68] |
3 | – | Lung inflammation | Acellular bronchial lavage Oral taxa analysis | Aspiration- derived microbiota | (2016) [69] |
Inflammatory cytokines and proinflammatory Th17 phenotype |
| ||||
4 | Compro mised oral health | – | Prospective nonrandomized study in ICU patients | Methicillin- resistant Staphylococcus aureus, Pseudomonas aeruginosa and ten genera of Gram-negative bacilli | (1992) [70] |
5 | Poor dental health | Hospital acquired pneumonia | Plaque index scores and quantitative cultures of dental plaques from ICU patients | Aerobic bacteria | (2004) [71] |
6 | – | Ventilator- associated pneumonia | Dental plaque and bronchoalveolar lavage sample from ICU patients undergoing mechanical ventilation | Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter species and enteric species | (2008) [72] |
7 | Oral care | Pneumonia | Oral health care Reduces risk of nosocomial pneumonia in elderly patient | – | (2002) [73] |
8 | Periodontitis | COPD | Cross-sectional study | Association Between periodontitis and COPD | (2018) [74] |
9 | Tooth loss Tooth decay Periodont itis. | Lung cancer | Nested case control study | – | (2019) [75] |
10 | Periodont itis | Asthma | A case control study analyzing periodontitis, oral microflora and asthma | Prevotella intermedia | (2020) [76] |
Table 2: Influence of oral health status and microbiome on respiratory diseases [66].