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Oral microbiology
Oral microbiology
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Thrush, a common condition caused by overgrowth of the fungus Candida albicans. Cases are characterized by growth of matted, yellow-white patches of fungus in the mouth.

Oral microbiology is the study of the microorganisms (microbiota) of the oral cavity and their interactions between oral microorganisms or with the host.[1] The environment present in the human mouth is suited to the growth of characteristic microorganisms found there. It provides a source of water and nutrients, as well as a moderate temperature.[2] Resident microbes of the mouth adhere to the teeth and gums to resist mechanical flushing from the mouth to stomach where acid-sensitive microbes are destroyed by hydrochloric acid.[2][3]

Anaerobic bacteria in the oral cavity include: Actinomyces, Arachnia (Propionibacterium propionicus), Bacteroides, Bifidobacterium, Eubacterium, Fusobacterium, Lactobacillus, Leptotrichia, Peptococcus, Peptostreptococcus, Propionibacterium, Selenomonas, Treponema, and Veillonella.[4][needs update] The most commonly found protists are Entamoeba gingivalis and Trichomonas tenax.[5] Genera of fungi that are frequently found in the mouth include Candida, Cladosporium, Aspergillus, Fusarium, Glomus, Alternaria, Penicillium, and Cryptococcus, among others.[6] Bacteria accumulate on both the hard and soft oral tissues in biofilms. Bacterial adhesion is particularly important for oral bacteria.

Oral bacteria have evolved mechanisms to sense their environment and evade or modify the host. Bacteria occupy the ecological niche provided by both the tooth surface and mucosal epithelium.[7][8] Factors of note that have been found to affect the microbial colonization of the oral cavity include the pH, oxygen concentration and its availability at specific oral surfaces, mechanical forces acting upon oral surfaces, salivary and fluid flow through the oral cavity, and age.[8] Interestingly, it has been observed that the oral microbiota differs between men and women in conditions of oral health, but especially during periodontitis.[9] However, a highly efficient innate host defense system constantly monitors the bacterial colonization and prevents bacterial invasion of local tissues. A dynamic equilibrium exists between dental plaque bacteria and the innate host defense system.[7] Of particular interest is the role of oral microorganisms in the two major dental diseases: dental caries and periodontal disease.[7]

Oral microflora

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Oral Microbiology Lab Analysis Report.[10]

The oral microbiome, mainly comprising bacteria which have developed resistance to the human immune system, has been known to impact the host for its own benefit, as seen with dental cavities. The environment present in the human mouth allows the growth of characteristic microorganisms found there. It provides a source of water and nutrients, as well as a moderate temperature.[2] Resident microbes of the mouth adhere to the teeth and gums to resist mechanical flushing from the mouth to stomach where acid-sensitive microbes are destroyed by hydrochloric acid.[2][3]

Anaerobic bacteria in the oral cavity include: Actinomyces, Arachnia, Bacteroides, Bifidobacterium, Eubacterium, Fusobacterium, Lactobacillus, Leptotrichia, Peptococcus, Peptostreptococcus, Propionibacterium, Selenomonas, Treponema, and Veillonella.[4] In addition, there are also a number of fungi found in the oral cavity, including: Candida, Cladosporium, Aspergillus, Fusarium, Glomus, Alternaria, Penicillium, and Cryptococcus.[11] The oral cavity of a new-born baby does not contain bacteria but rapidly becomes colonized with bacteria such as Streptococcus salivarius. With the appearance of the teeth during the first year colonization by Streptococcus mutans and Streptococcus sanguinis occurs as these organisms colonise the dental surface and gingiva. Other strains of streptococci adhere strongly to the gums and cheeks but not to the teeth. The gingival crevice area (supporting structures of the teeth) provides a habitat for a variety of anaerobic species. Bacteroides and spirochetes colonize the mouth around puberty.[7]

Ecological sites for oral microbiota

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As a diverse environment, a variety of organisms can inhabit unique ecological niches present in the oral cavity including the teeth, gingiva, tongue, cheeks, and palates.[12]

Dental plaque

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The dental plaque is made up of the microbial community that is adhered to the tooth surface; this plaque is also recognized as a biofilm. While it is said that this plaque is adhered to the tooth surface, the microbial community of the plaque is not directly in contact with the enamel of the tooth. Instead, bacteria with the ability to form attachments to the acquired pellicle, which contains certain salivary proteins, on the surface of the teeth, begin the establishment of the biofilm. Upon dental plaque maturation, in which the microbial community grows and diversifies, the plaque is covered in an interbacterial matrix.[8]

Dental calculus

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The calculus of the oral cavity is the result of mineralization of and around dead microorganisms; this calculus can then be colonized by living bacteria. Dental calculus can be present on supragingival and subgingival surfaces.[8]

Oral mucosa

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The mucosa of the oral cavity provides a unique ecological site for microbiota to inhabit. Unlike the teeth, the mucosa of the oral cavity is frequently shedding and thus its microbial inhabitants are both kept at lower relative abundance than those of the teeth but also must be able to overcome the obstacle of the shedding epithelia.[8]

Tongue

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Unlike other mucosal surfaces of the oral cavity, the nature of the top surface of the tongue, due in part to the presence of numerous papillae, provides a unique ecological niche for its microbial inhabits. One important characteristic of this habitat is that the spaces between the papillae tend to not receive much, if any, oxygenated saliva, which creates an environment suitable for microaerophilic and obligate anaerobic microbiota.[13]

Acquisition of oral microbiota

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Acquisition of the oral microbiota heavily depends on the route of delivery as an infant – vaginal versus caesarian; upon comparing infants three months after birth, infants born vaginally were reported to have higher oral taxonomic diversity than their cesarean-born counterparts.[14][12] Further acquisition is determined by diet, developmental accomplishments, general lifestyle habits, hygiene, and the use of antibiotics.[14] Breastfed infants are noted to have higher oral lactobacilli colonization than their formula-fed counterparts.[12] Diversity of the oral microbiome is also shown to flourish upon the eruption of primary teeth and later adult teeth, as new ecological niches are introduced to the oral cavity.[12][14]

Factors of microbial colonization

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Saliva plays a considerable role in influencing the oral microbiome.[15] More than 800 species of bacteria colonize oral mucus, 1,300 species are found in the gingival crevice, and nearly 1,000 species comprise dental plaque. The mouth is a rich environment for hundreds of species of bacteria since saliva is mostly water and plenty of nutrients pass through the mouth each day. When kissing, it takes only 10 seconds for no less than 80 million bacteria to be exchanged by the passing of saliva. However, the effect is transitory, as each individual quickly returns to their own equilibrium.[16][17]

Due to progress in molecular biology techniques, scientific understanding of oral ecology is improving. Oral ecology is being more comprehensively mapped, including the tongue, the teeth, the gums, salivary glands, etc. which are home to these communities of different microorganisms.[18]

The host's immune system controls the bacterial colonization of the mouth and prevents local infection of tissues. A dynamic equilibrium exists notably between the bacteria of dental plaque and the host's immune system, enabling the plaque to stay behind in the mouth when other biofilms are washed away.[19]

In equilibrium, the bacterial biofilm produced by the fermentation of sugar in the mouth is quickly swept away by the saliva, except for dental plaque. In cases of imbalance in the equilibrium, oral microorganisms grow out of control and cause oral diseases such as tooth decay and periodontal disease. Several studies have also linked poor oral hygiene to infection by pathogenic bacteria.[20]

Role in health

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The oral microbiota is largely related to systemic health, and disturbances in the oral microbiota can lead to diseases in both the oral cavity and the rest of the body.[21] There are many factors that influence the diversity of the oral microbiota, such as age, diet, hygiene practices, and genetics.[22]

Of particular interest is the role of oral microorganisms in the two major dental diseases: dental caries and periodontal disease.[7] There are many factors of oral health which need to be preserved in order to prevent pathogenesis of the oral microbiota or diseases of the mouth. Dental plaque is the material that adheres to the teeth and consists of bacterial cells (mainly S. mutans and S. sanguis), salivary polymers and bacterial extracellular products. Plaque is a biofilm on the surfaces of the teeth. This accumulation of microorganisms subject the teeth and gingival tissues to high concentrations of bacterial metabolites which results in dental disease. If not taken care of, via brushing or flossing, the plaque can turn into tartar (its hardened form) and lead to gingivitis or periodontal disease. In the case of dental cavities, proteins involved in colonization of teeth by Streptococcus mutans can produce antibodies that inhibit the cariogenic process which can be used to create vaccines.[19]

Bacteria species typically associated with the oral microbiota have been found to be present in women with bacterial vaginosis.[23] Genera of fungi that are frequently found in the mouth include Candida, Cladosporium, Aspergillus, Fusarium, Glomus, Alternaria, Penicillium, and Cryptococcus, among others.[6]

Additionally, research has correlated poor oral health and the resulting ability of the oral microbiota to invade the body to affect cardiac health as well as cognitive function.[20] High levels of circulating antibodies to oral pathogens Campylobacter rectus, Veillonella parvula and Prevotella melaninogenica are associated with hypertension in human.[24]

Importance of dental hygiene

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One of the most important factors in promoting optimal oral microbiota health is the use of good oral hygiene practices. To prevent any possible complication from an altered oral microbiota, it is important to brush and floss every day, schedule regular cleanings, eat a healthy diet, and replace toothbrushes frequently.[25] Dental plaque is associated with two extremely common oral diseases, dental caries and periodontal disease.[26] Consistent toothbrushing and flossing is essential for disrupting harmful plaque formation. Research has shown that flossing is associated with a decrease in the bacteria Streptococcus mutans which has been shown to be involved in cavity formation.[27] Insufficient brushing and flossing can lead to gum and tooth disease, and eventually tooth loss.[25]

In addition, poor dental hygiene has been linked to conditions such as osteoporosis, diabetes and cardiovascular diseases.[25]

Issues and areas of research

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The oral environment (temperature, humidity, pH, nutrients, etc.) impacts the selection of adapted (and sometimes pathogenic) populations of microorganisms.[28] For a young person or an adult in good health and with a healthy diet, the microbes living in the mouth adhere to mucus, teeth and gums to resist removal by saliva. Eventually, they are mostly washed away and destroyed during their trip through the stomach.[28][29] Salivary flow and oral conditions vary person-to-person, and also relative to the time of day and whether or not an individual sleeps with their mouth open. From youth to old age, the entire mouth interacts with and affects the oral microbiome.[30] Via the larynx, numerous bacteria can travel through the respiratory tract to the lungs. There, mucus is charged with their removal. Pathogenic oral microflora have been linked to the production of factors which favor autoimmune diseases such as psoriasis and arthritis, as well as cancers of the colon, lungs and breasts.[31]

Intercellular communication

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Most of the bacterial species found in the mouth belong to microbial communities, called biofilms, a feature of which is inter-bacterial communication. Cell–cell contact is mediated by specific protein adhesins and often, as in the case of inter-species aggregation, by complementary polysaccharide receptors. Another method of communication involves cell–cell signalling molecules, which are of two classes: those used for intra-species and those used for inter-species signalling. An example of intra-species communication is quorum sensing. Oral bacteria have been shown to produce small peptides, such as competence stimulating peptides, which can help promote single-species biofilm formation. A common form of inter-species signalling is mediated by 4, 5-dihydroxy-2, 3-pentanedione (DPD), also known as autoinducer-2 (Al-2).[32]

Evolution

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The evolution of the human oral microbiome can be traced through time via the sequencing of dental calculus (essentially fossilized dental plaque).[33]

As mentioned in prior sections, the human oral microbiome has important implications for the health and wellness of human beings overall, and is often the only surviving health record for ancient populations.

The oral microbiome has evolved over time alongside humans, in response to changes in diet, lifestyle, environment, and even the advent of cooking.[33] There have also been similarities in oral microbiota across hominins, as well as other primate species. While a core microbiome consisting of specific bacteria exists across most individuals, significant variation can arise depending on an individual’s unique environment, lifestyle, physiology, and heritage.[34]

Considering that oral bacteria are transferred vertically from primary caregivers in early childhood, and horizontally between family members later in life, archaeological dental calculus is a unique way to trace population structure, movement, and admixture between ancient cultures, as well as the spread of disease.[33]

Pre-Mesolithic

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Relationship to primates

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Ancient humans are thought to have maintained a much different oral microbiome landscape than non-human primates, despite having a shared environment. Existing data has found that chimpanzees maintain higher levels of Bacteroidetes and Fusobacteria, while humans have greater proportions of Firmicutes and Proteobacteria.[33] Human oral microbiota have also been found to be less diverse when compared with other primates.[33]

Relationship to hominins

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Of the hominins (Homo erectus, Neanderthals, Denisovans) Neanderthal oral microbiomes have been studied in the greatest detail. A cluster of oral microbiota has been found to be shared across Spanish Neanderthals, foraging humans from ~3000 years ago, and a single wild-caught chimpanzee. Similarities have also been found between a meat-eating Neanderthal in Belgium, and hunter humans in Europe and Africa. Ozga et al. (2019) found that Neanderthals and humans share similar oral microbiota, and are more alike to each other than to chimpanzees. Weyrich (2021) finds that these observations suggest humans shared an oral microbiota with Neanderthals until at least 3000 years ago. While it is possible that humans and Neanderthals shared oral microbiota from the moment of separation (~700,000 years ago) until their extinction, Weyrich finds that an equally likely hypothesis is that convergent evolution accounted for similar oral microbiotas across Neanderthals and humans for that period.[35]

Major shifts through archaeological periods

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The human oral microbiome has been a subject of increasing scientific scrutiny, especially in understanding its evolutionary journey. The oral microbiome has undergone significant shifts in composition, particularly during key historical periods like the Neolithic and the Industrial Revolution.

The Neolithic revolution: a turning point

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The Neolithic period began around 10,000 years ago and marked a significant turning point in human history. This era saw the shift from a hunter-gatherer lifestyle to agriculture and farming. One of the most significant changes during this period was the adoption of carbohydrate-rich diets, particularly the consumption of domesticated cereals like wheat and barley. This shift had a profound impact on the oral microbiome. The increase in fermentable carbohydrates led to a surge in dental caries, a common oral health issue. Additionally, the Neolithic period also witnessed a reduction in microbial diversity in the oral environment.[33]

The Medieval period: a period of stability

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Transitioning from the Neolithic to the Medieval period, which began around 400 years ago, there was little change in the composition of the oral microbiota. This period of stability suggests that despite advancements in agriculture and societal structures, the oral microbiome remained relatively constant. This period did not bring about significant shifts in oral microbial communities, indicating a sort of equilibrium had been reached.[33]

The Industrial Revolution: a modern dilemma

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The Industrial Revolution, starting around 1850, brought about another significant shift in human lifestyle and, consequently, the oral microbiome. The widespread availability of industrially processed flour and sugar led to a predominance of cariogenic bacteria in the oral environment. This shift has persisted to the present day, making the modern oral microbiome less diverse than ever before, rendering it less resilient to perturbations in the form of dietary imbalances or invasion by pathogenic bacterial species.[33]

Implications for modern health

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The shifts in the oral microbiome through time have significant implications for modern health. The current lack of diversity in the oral microbiome makes it more susceptible to imbalances and pathogenic invasions. This, in turn, can lead to a range of oral and systemic health issues, from dental caries to cardiovascular disease. Dental caries affects between 60 and 90% of children and adults in industrialized countries, and has a more severe effect on less industrialized countries with less capable healthcare systems.[36] An understanding of the oral microbiome, via an examination of the evolution of the oral microbiome, can help science understand past errors and help inform the best path forward in sustainable healthcare interventions that work proactively with the body's natural systems, rather than fighting them with intermittent reactive interventions.

Graphic Showing Systemic Effects of Human Oral Microbiome
Systemic effects of human oral microbiome.[34]

See also

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References

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Revisions and contributorsEdit on WikipediaRead on Wikipedia

Oral microbiology

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from Grokipedia
Oral microbiology is the study of the diverse microorganisms inhabiting the oral cavity, encompassing , fungi, viruses, and , and their critical roles in maintaining oral health or contributing to diseases such as dental caries and periodontitis. This field examines the complex microbial communities, often forming biofilms on surfaces like teeth, gums, tongue, and mucosa, which comprise over 700 prokaryotic species across major phyla including Actinobacteria, Bacteroidetes, Firmicutes, Fusobacteria, and Proteobacteria. In healthy states, these microbes exist in a symbiotic equilibrium, supporting functions like nutrient processing and immune modulation, but —shifts in composition driven by factors such as diet, , antibiotics, and —can lead to pathogenic overgrowth. Notable pathogens include in caries formation and in periodontitis, highlighting the ecological dynamics of polymicrobial interactions. Beyond oral pathologies, oral microbiology has revealed profound links to systemic health, with dysbiotic oral communities implicated in conditions like cardiovascular disease, diabetes, and even cancers through mechanisms such as inflammation and microbial translocation. Advances in "-omics" technologies, including metagenomics and metatranscriptomics since the 1990s, have revolutionized the field by enabling comprehensive profiling of these communities and their functional roles. Key habitats show site-specific diversity: for instance, streptococci dominate the dorsum of the tongue and hard palate, while anaerobes like Fusobacterium nucleatum prevail in subgingival plaques. Fungi such as Candida albicans and viruses including herpesviridae further contribute to this ecosystem, with interactions governed by coaggregation and quorum sensing. Understanding these elements underscores the oral cavity's status as a microbial hotspot, second only to the gut in complexity, and informs preventive strategies like probiotics and targeted antimicrobials.

Composition and Diversity of Oral Microbiota

Bacterial Components

The oral cavity harbors an estimated 10⁹–10¹⁰ total bacteria, including 10⁸–10⁹ per ml in saliva and dense populations in dental plaque, representing an intermediate bacterial load among body sites such as hands and anus. The oral microbiome is predominantly bacterial, encompassing over 3,400 identified species that form the foundational microbial community in the human mouth. Recent high-quality genomic catalogs as of 2025 have expanded this diversity, identifying 3,426 species including over 2,000 novel ones. These bacteria exhibit high diversity, with the five dominant phyla—Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Fusobacteria—collectively accounting for approximately 80% of the taxa. Firmicutes often represent 30-50% of the composition, followed by Bacteroidetes at 15-30%, Actinobacteria at 10-20%, Proteobacteria at 5-15%, and Fusobacteria at lower but significant levels. This phylum-level distribution reflects the ecological balance maintained in healthy states, where bacteria adapt to varying oxygen levels and nutrient availability across oral surfaces. Core bacterial species play pivotal roles in this ecosystem, with Streptococcus spp. standing out as early colonizers and primary occupants in healthy microbiomes, comprising 20-40% of the total abundance. Specific examples include , which facilitates initial biofilm formation, and , known for its acidogenic properties that contribute to enamel demineralization in cariogenic environments. Veillonella spp. typically constitute 5-20% in healthy conditions, often co-occurring with streptococci to metabolize into less harmful byproducts, thus supporting microbial stability. Actinomyces spp. account for 5-15% of the community, aiding in plaque maturation through polysaccharide production. In contrast, spp. maintain lower abundances (around 5%) in health but exhibit functional versatility in processes. In diseased states, such as dental caries and periodontitis, bacterial abundances shift markedly; for instance, S. mutans can rise to over 60% in carious lesions due to its enhanced acid production, while Prevotella spp. may increase to 20-30%, promoting through inflammatory responses. The community also features a predominance of anaerobes, with comprising 70-80% overall and facultative anaerobes or aerobes making up the remainder; notable examples include , an that thrives in low-oxygen niches and elevates in via factors like gingipains. Functionally, streptococci drive initial coverage by adhering to salivary pellicles and generating acidic microenvironments that select for acid-tolerant successors, underscoring their role in both and pathogenesis.

Non-Bacterial Microorganisms

The oral microbiota is predominantly bacterial, yet non-bacterial microorganisms such as fungi, viruses, , and constitute a diverse, albeit less abundant, component that contributes to microbial through unique metabolic and interactive roles. Fungi in the oral cavity, collectively termed the mycobiome, are primarily represented by from the phyla and , encompassing approximately 100 identified across healthy individuals. dominates the oral mycobiome, often comprising the majority of detectable fungal sequences in and plaque samples. These fungi engage in ecological interactions with , such as physical bridging between Candida and streptococci, which can influence community structure and stability. The oral virome includes a variety of viruses that modulate microbial populations, with bacteriophages playing a key role in lysing host bacteria to regulate community dynamics. Bacteriophages targeting streptococci, such as those infecting , have been isolated from oral samples and contribute to controlling bacterial proliferation through host cell . Eukaryotic viruses like type 1 (HSV-1), Epstein-Barr virus (EBV), and human papillomaviruses are also prevalent in the oral virome, persisting in epithelial cells and potentially altering local microbial environments via immune modulation. Archaea represent a minor fraction of the oral , typically accounting for 1-2% of total microbial abundance in healthy individuals, with Methanobrevibacter oralis as the predominant species. This participates in hydrogen metabolism by consuming hydrogen produced by bacterial , facilitating interspecies syntrophy and influencing overall microbial energetics in anaerobic niches like the subgingival space. Protozoa are rare contributors to the oral ecosystem, with observed primarily in periodontal pockets where it exhibits phagocytic activity toward host cells and bacteria. Recent metagenomic studies from 2025 have uncovered extensive bacterial-fungal-viral interactions in the oral microbiome, highlighting over 500 potential cross-kingdom associations that underscore the interconnected nature of these microbial communities.

Habitats and Ecology in the Oral Cavity

Hard Tissue Sites

Hard tissue sites in the oral cavity, primarily the surfaces including enamel and , provide stable, non-shedding substrates for microbial and development. Supragingival plaque, formed above the gingival margin on enamel, begins with the attachment of early colonizers such as and species, which bind to the acquired pellicle—a layer on the surface. These initial create a foundation for subsequent , leading to multilayered biofilms with thicknesses typically ranging from 20 to 50 μm in early stages, though mature plaques can exceed 100 μm in depth. Over time, particularly within 48 hours, the community diversifies as secondary colonizers adhere via coaggregation, resulting in complex structures dominated by facultative anaerobes that lower the local and enable stricter anaerobes to thrive. Subgingival plaque, located below the gingival margin along the and in periodontal pockets, exhibits a distinct ecological shift toward anaerobiosis compared to supragingival sites. Key inhabitants include anaerobic pathogens such as , , and , which form synergistic complexes that contribute to periodontal . Environmental conditions in these niches feature gradients, with neutral salivary influences (around 7.0) transitioning to slightly alkaline microenvironments (up to 8.0-8.5) due to proteolytic activity and from substrates in gingival crevicular fluid. This alkalinity, combined with reduced oxygen availability, favors the proliferation of obligate anaerobes and exacerbates tissue destruction. Dental calculus, or tartar, represents mineralized supragingival or subgingival plaque, serving as a persistent reservoir for microbial communities. It consists of approximately 70-90% inorganic material, predominantly crystals such as and octacalcium phosphate, with the remainder comprising bacterial remnants and organic matrix. Mineralization occurs rapidly, with up to 50% within days of plaque formation, rendering it resistant to mechanical disruption. Pathogens like can embed within , evading host defenses and contributing to chronic infections such as . Ecological gradients across hard tissue sites profoundly influence microbial distribution, particularly oxygen levels that decrease from the aerobic enamel surfaces to the more anaerobic cementum regions in the subgingival environment. Facultative anaerobes like streptococci predominate in oxygen-rich supragingival zones, consuming O₂ and creating reducing conditions that permit colonization by obligate anaerobes deeper in the or along root surfaces. These gradients, along with variations in flow and , establish distinct niches that drive community succession and maintain stability on teeth.

Soft Tissue Sites

The , comprising the inner lining of the cheeks, lips, and other soft tissues, hosts a diverse array of epithelial-associated , prominently including genera such as Rothia (from the Actinobacteria) and Neisseria (from Proteobacteria), which adhere to the mucosal surface and contribute to the resident microbial community. These form loose associations with the , where of surface cells leads to a rapid turnover of the microbial populations every 5-7 days, promoting a dynamic equilibrium between resident and transient . This shedding mechanism distinguishes mucosal habitats from more stable hard tissue biofilms, as it continually disrupts established communities and facilitates recolonization by salivary transients. The dorsum of the represents a key niche characterized by its rough filiform papillae, which provide an extensive surface area harboring over 200 bacterial species, with a predominance of anaerobic genera such as Prevotella and Veillonella. These anaerobes thrive in the microaerophilic environment of the papillae crypts, forming multilayered biofilms that include desquamated epithelial cells and food debris, and they play a significant role in producing volatile sulfur compounds (VSCs) like and methyl mercaptan, which are primary contributors to intra-oral halitosis. The tongue's microbial density is notably higher than in other mucosal sites, supporting a stable core of anaerobes while allowing transient aerobes to pass through during oral activities. The salivary microbiome, derived from whole saliva, primarily consists of transient species that originate from various oral surfaces, including Gemella species, which are frequently detected as part of the core salivary community alongside other commensals like Streptococcus and Neisseria. These transients are suspended in saliva and subject to frequent clearance through swallowing and expectoration, resulting in a less adherent population compared to tissue-bound microbes. Salivary pH, buffered by bicarbonate secreted from salivary glands, maintains a neutral range (approximately 6.2-7.6) that favors the colonization and survival of these acid-sensitive species while inhibiting overgrowth of pathogens. The cheeks (buccal mucosa) and lips serve as aerobic sites with relatively lower microbial , estimated at around 10^6 colony-forming units (CFU) per mL of sampled material, in contrast to the higher densities in supragingival plaque. These areas are dominated by facultative anaerobes such as species (e.g., S. salivarius and S. mitis) and Staphylococcus species, which exploit the oxygen-rich environment near the oral opening and form sparse, loosely attached layers influenced by mechanical from mastication and speech. The transient nature here is accentuated by constant exposure to air and saliva flow, limiting maturation and favoring commensal aerobes over strict anaerobes.

Acquisition and Succession of Oral Microbiota

Initial Colonization

The oral cavity of a newborn is initially sterile, with microbial colonization beginning immediately at birth through vertical transmission from the mother. In vaginally delivered infants, the pharynx and oral cavity are primarily seeded with bacteria from the maternal vaginal microbiota, including Lactobacillus and Prevotella species, which belong to the Firmicutes and Bacteroidetes phyla, respectively. In contrast, infants born via cesarean section acquire skin-associated microbes, such as Staphylococcus and Propionibacterium species, leading to a distinct initial community composition that differs from maternal vaginal flora. This mode-of-delivery effect shapes early oral assembly, with pharyngeal aspirates in vaginally delivered neonates showing greater similarity to maternal vaginal and rectal microbiomes compared to those in cesarean-delivered neonates. Breastfeeding further facilitates vertical transmission of maternal oral , particularly streptococci, promoting the establishment of a diverse early . Maternal and serve as key vectors, transferring species like and , which become abundant in breastfed infants (e.g., S. salivarius comprising 10–15% of the community at 3 months). By 3 months of age, the infant oral microbiota typically includes around 65 operational taxonomic units (OTUs) per individual, encompassing dozens of species dominated by early colonizers such as and , with detected in approximately 28% of breastfed infants. This period marks rapid diversification, with up to 95% of infant oral species shared with maternal microbiomes by day 3, reflecting intense mother-to-infant transmission. The introduction of solid foods during , typically around 6 months, drives a compositional shift toward saccharolytic capable of fermenting complex carbohydrates, such as and Veillonella species, increasing overall microbial richness and complexity. Concurrently, the eruption of primary teeth at approximately 6–8 months provides new hard surfaces that enable the formation of biofilms, further supporting the adhesion and proliferation of these communities. By age 1, mother-infant oral microbiomes exhibit 70–90% similarity in key taxa, including high sharing rates for (around 70–88% of pairs), underscoring the lasting impact of during this foundational phase.

Lifespan Dynamics

During , hormonal shifts, particularly those associated with and testosterone, drive notable changes in the oral composition. The frequency of Actinomyces odontolyticus increases significantly, correlating with pubertal development markers such as in girls (Tanner scores, p < 0.01) and testicular growth in boys (p < 0.01). These alterations contribute to heightened gingival , as total bacterial counts peak shortly after onset before declining. In young adulthood, around 20-30 years of age, the oral achieves peak diversity, encompassing over 700 bacterial species, reflecting a stable, mature community post-initial colonization. As individuals age, the oral microbiota undergoes progressive shifts toward reduced diversity and dysbiosis, particularly in the elderly. Alpha-diversity declines notably after age 60, with a loss of beneficial anaerobes such as Fusobacterium, Leptotrichia, and Selenomonas, while opportunistic pathogens like Enterobacteriaceae rise in abundance. Xerostomia, common in older adults due to factors like medication or salivary gland atrophy, exacerbates this by contributing to a 30-50% decline in microbial species richness, favoring acidogenic species such as Streptococcus mutans and Lactobacillus spp. These changes promote chronic inflammation and frailty, with enteropathogens like Lactobacillus and Streptococcus anginosus becoming dominant. Sex and racial variations further modulate lifespan dynamics of the oral microbiota, as evidenced by 2025 NHANES data from over 9,000 U.S. adults. Males exhibit higher Shannon diversity and elevated abundances of genera like and Atopobium compared to females, potentially influenced by sex hormones including , which correlates with increased fungal elements in postmenopausal women due to estrogen decline. Ethnic differences are pronounced, with non-Hispanic Black and individuals showing higher amplicon sequence variants (134-137 ASVs) than (124 ASVs), including variations in abundance—such as Prevotella 7 at 8% relative abundance overall but differing by group, contributing to disparities in community structure across racial lines. Pregnancy induces temporary, hormone-mediated perturbations in the oral , primarily driven by elevated and progesterone levels. These shifts favor the proliferation of anaerobes like , whose abundance positively correlates with maternal hormone concentrations and gingival inflammation severity (p = 0.001 for , p = 0.003 for progesterone). Such changes, peaking in the third trimester, enhance plaque accumulation and overgrowth, though the typically reverts postpartum.

Factors Influencing Microbial Colonization

Host Intrinsic Factors

Host intrinsic factors play a pivotal role in shaping the oral microbiota by influencing microbial adhesion, survival, and immune recognition through genetic, immunological, physiological, and structural mechanisms. Genetic variations in host genes directly affect the molecular interactions with oral bacteria. For instance, the MUC7 gene encodes salivary mucin MUC7, also known as salivary agglutinin, which binds to surface proteins on streptococci such as Streptococcus sanguinis and Streptococcus mutans, promoting their aggregation and clearance from the oral cavity. Similarly, polymorphisms in the FUT2 gene determine secretor status, which modulates fucosylation of glycoproteins in saliva and epithelial surfaces and has been associated with variations in the composition of the oral microbiome. Immune modulation by the host further regulates microbial colonization in the oral cavity. Salivary secretion of (IgA) constitutes a major component of mucosal immunity, with total daily production of secretory IgA across mucosal sites estimated at approximately 3 g, a portion of which is directed to the oral environment to coat and neutralize microbes. In , IgA binds to a substantial fraction of oral bacteria, facilitating their and preventing adherence to mucosal surfaces, thereby maintaining microbial . Additionally, Toll-like receptors (TLRs), particularly TLR4 expressed on oral epithelial cells, recognize (LPS) from like , triggering innate immune responses that limit bacterial overgrowth and translocation. The composition of saliva provides intrinsic antimicrobial defenses that influence microbial survival. Proteins such as α-amylase, , and histatins exhibit direct bactericidal and fungicidal activities; hydrolyzes bacterial cell walls, histatins disrupt fungal membranes, and amylase contributes to antibacterial effects through generation. Salivary flow rate, typically 0.3–0.4 mL/min under unstimulated conditions, mechanically clears microbes and dilutes potential pathogens, with variations affecting antimicrobial efficacy. Epithelial barriers in the serve as physical and chemical obstacles to microbial invasion. proteins, including claudins (e.g., claudin-1), form selective paracellular seals in oral epithelial cells, preventing bacterial translocation into deeper tissues while allowing nutrient passage. The oral cavity maintains within a range of 6.7–7.4 through salivary buffering, which inhibits acid-tolerant pathogens and supports a balanced .

Extrinsic Environmental Factors

Extrinsic environmental factors play a pivotal role in shaping the structure and dynamics of the by altering nutrient availability, microbial adhesion, and community balance. These modifiable influences, including diet, practices, antimicrobial exposures, and socioeconomic conditions, can promote or enhance resilience in the . Unlike intrinsic host traits, these factors are amenable to intervention, offering opportunities to mitigate microbial shifts that contribute to oral health outcomes. Dietary components significantly influence oral microbial colonization, particularly through the provision of fermentable substrates. , a common dietary sugar, promotes adhesion of to tooth surfaces by serving as a substrate for glucosyltransferases (), which synthesize adhesive glucans that facilitate formation and bacterial aggregation. Similarly, frequent intake of fermentable carbohydrates, such as those in sugary foods and beverages, leads to rapid acid production by plaque bacteria, lowering local to below 5.5 and selectively favoring the growth of aciduric species like S. mutans and lactobacilli over less tolerant microbes. This pH drop creates selective pressure that enriches cariogenic communities, as aciduric bacteria thrive in the resulting acidic microenvironment adjacent to dental hard tissues. Oral hygiene practices exert a direct mechanical and chemical impact on microbial and composition. Regular toothbrushing effectively disrupts plaque accumulation, removing approximately 60% of supragingival plaque per session through abrasion and shear forces that dislodge bacterial aggregates. Interdental flossing complements this by targeting interproximal sites and helping to prevent the maturation of biofilms that harbor pathogenic species. , commonly incorporated in toothpastes and mouthrinses, inhibits bacterial by binding to , a key enzyme that converts 2-phosphoglycerate to phosphoenolpyruvate, thereby reducing acid production and limiting energy availability for acidogenic . These combined effects maintain a balanced by suppressing overgrowth of plaque-associated pathogens. Antimicrobial exposures from systemic or local sources can profoundly disrupt the oral microbial equilibrium, often favoring opportunistic . Antibiotics like amoxicillin, frequently prescribed for oral infections, selectively deplete anaerobic bacteria such as and species, creating ecological vacuums that enable fungal overgrowth, including Candida albicans due to reduced bacterial competition. Tobacco smoking, another prevalent exposure, alters the oral environment through and other compounds, significantly increasing the abundance of Porphyromonas gingivalis—a keystone periodontal —by enhancing its formation and adherence to host tissues, with studies showing up to several-fold elevations in smokers compared to non-smokers. These disruptions reduce overall microbial diversity and promote inflammation-associated communities. Socioeconomic factors indirectly modulate the oral microbiota via disparities in access to preventive care and hygiene resources. Lower correlates with reduced access to dental services and oral , leading to diminished microbial diversity and shifts toward dysbiotic profiles dominated by caries- or periodontitis-associated taxa. For instance, individuals in low-income brackets often exhibit lower in their oral microbiomes, attributable to inconsistent practices and poorer dietary quality, which exacerbate the accumulation of pathogenic biofilms. Addressing these inequities through improved access can help restore balanced microbial communities.

Microbial Interactions and Communication

Biofilm Formation

The formation of oral biofilms begins with the rapid adsorption of salivary proteins to the enamel surface, creating the acquired pellicle. This conditioning film develops within seconds of exposure to , serving as the initial attachment site for microbial colonization. Key proteins such as statherin, a histidine-rich , bind selectively to , the primary mineral component of enamel, providing a stable interface that modulates subsequent bacterial . Other salivary components, including acidic proline-rich proteins and histatins, contribute to this layer, which forms a proteinaceous matrix approximately 0.1-1 micrometer (100-1000 nm) thick. Co-adhesion follows pellicle formation, involving sequential attachment of bacterial species. Primary colonizers, predominantly streptococci such as Streptococcus oralis and Streptococcus gordonii, adhere via specific adhesins like pili and surface proteins that interact with pellicle components. These early settlers create binding sites for secondary colonizers, such as Veillonella spp., which attach through lectin-mediated interactions with carbohydrate receptors on primary bacteria. This staged process is facilitated by salivary glycoproteins that bridge bacterial cells, leading to the accumulation of an extracellular polymeric substance (EPS) matrix primarily composed of polysaccharides, proteins, and DNA, which can constitute up to 90% of the biofilm's total mass. As biofilms mature, they develop a complex three-dimensional architecture characterized by mushroom-shaped clusters and water channels that enable nutrient and waste removal. This structural , occurring over hours to days, is influenced by salivary flow, which exerts that disperses loosely attached cells while promoting the retention of more adherent communities. Site-specific variations in plaque architecture arise due to differences in local shear forces and substrate properties. In supragingival regions, prolonged maturation can lead to integration, where bacterial enzymes like , produced by species such as and certain streptococci, dephosphorylate organic substrates to provide inorganic ions, while ureolytic activity raises local through ammonia production from , facilitating the precipitation of minerals onto the EPS matrix. This mineralization process transforms portions of the into hardened deposits, embedding viable bacteria within crystalline structures.

Quorum Sensing Mechanisms

Quorum sensing (QS) in oral microbiology refers to the process by which microbial cells communicate through the production and detection of diffusible signaling molecules, known as autoinducers, to coordinate behaviors such as expression and maturation in response to . In the oral cavity, this intercellular signaling is crucial for the polymicrobial communities inhabiting sites like , enabling both cooperative and competitive interactions among bacteria and fungi. Key QS mechanisms involve species-specific and interspecies signals that regulate thresholds, influencing the dynamics of oral biofilms, including their structural assembly and maturation. One prominent interspecies QS signal in oral bacteria is autoinducer-2 (AI-2), a furanosyl borate diester molecule that facilitates communication across diverse species. AI-2 is synthesized via the LuxS enzyme, which is conserved in many oral streptococci such as Streptococcus gordonii and Streptococcus mutans, where it modulates carbohydrate metabolism and interspecies interactions within biofilms. In these streptococci, AI-2 is sensed by Rgg family transcriptional regulators, which respond to the signal at high cell densities to activate downstream genes involved in metabolic adaptation and community coordination. This LuxS/AI-2 system promotes polymicrobial harmony in the oral environment by synchronizing responses to nutrient availability and host factors. In Gram-positive oral pathogens like , intraspecies QS is mediated by the competence stimulating (CSP), a 21-amino-acid signaling that induces genetic competence for DNA uptake and production. The mature CSP, processed from a precursor by the SepM, binds to the membrane-bound receptor ComD, triggering a phosphorelay cascade that activates the response regulator ComE at a threshold of approximately 10^7 cells/mL. This density-dependent activation enhances S. mutans survival in competitive oral niches by facilitating and antimicrobial defense, thereby contributing to its dominance in cariogenic biofilms. Gram-negative bacteria occasionally present in the oral microbiome, such as opportunistic , employ acyl-homoserine lactones (AHLs) as QS signals to regulate and inhibit competing anaerobes. P. aeruginosa produces AHLs like N-3-oxododecanoyl-homoserine lactone via the LasI/R system, which at high densities activates genes for exoproducts that suppress growth of oral anaerobes such as Fusobacterium nucleatum and Porphyromonas gingivalis. This interkingdom interference disrupts anaerobic QS and integrity, allowing P. aeruginosa to colonize dysbiotic oral sites during conditions like periodontitis or antibiotic exposure. Fungal-bacterial crosstalk in the oral cavity involves quorum-sensing molecules from that modulate bacterial behaviors. C. albicans hyphae release , a alcohol serving as its own QS signal to inhibit hyphal elongation, which in turn disrupts bacterial QS systems. Specifically, farnesol interferes with peptide-based QS in streptococci like S. mutans by inhibiting processing and receptor activation, thereby reducing production and competence at concentrations relevant to oral biofilms. This antagonistic effect limits bacterial overgrowth, highlighting farnesol's role in maintaining microbial balance or promoting candidal dominance in mixed communities.

Roles in Health and Disease

Beneficial Functions

The oral microbiota contributes to host health by performing several protective functions that maintain ecological balance and prevent in the mouth. These include competitive exclusion of pathogens, modulation of immune responses, processing of nutrients to stabilize the local environment, and enhancement of physical barriers against invaders. Such symbiotic interactions underscore the microbiota's role in promoting oral . Commensal streptococci, such as Streptococcus sanguinis and Streptococcus salivarius, exert competitive exclusion by occupying ecological niches and producing bacteriocins that inhibit pathogenic species. For instance, these early colonizers generate hydrogen peroxide and antimicrobial peptides, limiting the proliferation of cariogenic bacteria like Streptococcus mutans. Bacteriocins, including mutacin produced by S. mutans itself under balanced conditions, further contribute to interspecies competition, favoring a diverse, non-pathogenic community. This mechanism helps prevent overgrowth of harmful microbes and supports a stable biofilm structure. Oral commensals also modulate the host to foster tolerance and reduce excessive . Certain stimulate the differentiation of regulatory T-cells (Tregs), which suppress pro-inflammatory responses and maintain epithelial integrity. Anaerobic members of the produce (SCFAs), such as and propionate, that bind to G protein-coupled receptors on immune cells, promoting pathways and limiting tissue damage in the gingival environment. In nutrient processing, the oral microbiota aids in maintaining a neutral and generating compounds. Veillonella species metabolize lactate produced by fermentative streptococci into weaker acids like and propionate, thereby preventing excessive acid accumulation that could lead to enamel demineralization. Additionally, nitrate-reducing bacteria, including Rothia and Neisseria, convert dietary to , which is further reduced to —a potent agent that inhibits growth and supports local defense. Finally, commensal biofilms enhance barrier functions by forming a protective matrix over the oral . Multi-species biofilms, involving organisms like and , create a stratified community that shields underlying tissues from invading microbes and promotes epithelial stratification for improved antimicrobial defense. This physical and functional barrier reinforces the host's innate immunity without triggering chronic .

Pathogenic Contributions to Oral Conditions

Microbial imbalances in the oral cavity, particularly favoring acid-tolerant or proteolytic and fungi, contribute to the onset and progression of several oral diseases by disrupting the ecological balance and promoting tissue damage. In dental caries, the shift toward acidogenic exemplifies how pathogens exploit dietary carbohydrates to create enamel-eroding environments. Similarly, in periodontitis, polymicrobial consortia drive inflammatory , while endodontic infections arise from persistent anaerobic penetration into root canals, and reflects opportunistic fungal overgrowth in vulnerable hosts. These conditions highlight the transition from commensal to pathogenic states through virulence mechanisms like production, enzymatic degradation, and invasive growth. Dental caries develops primarily through the action of acidogenic bacteria such as Streptococcus mutans and Lactobacillus species, which form biofilms on tooth surfaces and ferment dietary sugars into lactic acid, lowering the local pH. This acidification selects for acid-tolerant microbiota, perpetuating a cycle of enamel demineralization when the pH drops below 5.5 for prolonged periods, as described by the Stephan curve dynamics that illustrate postprandial pH fluctuations in plaque. S. mutans enhances this process by producing extracellular polysaccharides that stabilize the biofilm structure, allowing sustained acid retention and progressive subsurface lesions. Lactobacillus species further contribute in advanced caries stages, thriving in the low-pH niche and amplifying demineralization through their robust glycolytic metabolism. Periodontitis is strongly associated with the "red complex" of anaerobic bacteria—, , and —which synergistically invade subgingival plaque and trigger destructive inflammation. P. gingivalis, a keystone pathogen, produces gingipains, cysteine proteases that degrade host proteins, disrupt epithelial barriers, and modulate immune responses to evade clearance. These enzymes also activate inflammatory pathways, leading to activation via induction, which promotes alveolar bone loss and pocket deepening. The red complex bacteria interact within biofilms to enhance virulence; for instance, T. denticola and T. forsythia produce complementary factors like dentilisin and sialidases that facilitate nutrient acquisition and community stability, exacerbating tissue destruction. Endodontic infections typically involve mixed anaerobic consortia, with species playing a central role in primary and persistent infections by bridging other in biofilms and promoting formation. In primary infections, predominates, leveraging its adhesins to colonize necrotic pulp and create oxygen-depleted niches that favor anaerobes like Parvimonas micra and species. This polymicrobial invasion extends beyond the canal, eliciting periapical inflammation and abscesses through endotoxin release and immune evasion, often resulting in symptomatic swelling when breach the . Secondary infections, post-treatment, show elevated levels, underscoring its resilience in complex, treatment-resistant biofilms. Oral candidiasis arises from the overgrowth of Candida albicans, particularly in immunocompromised individuals, where hyphal morphogenesis enables invasive penetration of the mucosal . In healthy hosts, C. albicans exists as a commensal , but host factors like reduced salivary flow or T-cell deficiencies shift the balance, allowing formation on mucosal surfaces and dissemination of hyphae that secrete hydrolytic enzymes to degrade keratinized tissues. This dimorphic transition from to hyphal forms is a key trait, facilitating , tissue , and elicitation of chronic inflammation, often manifesting as pseudomembranous plaques or erythematous lesions in the oral cavity. In severe cases, such as HIV-associated , hyphal correlates with deeper mucosal damage and increased fungal burden.

Associations with Systemic Health

Dysbiosis and Oral Diseases

in the oral is characterized by a perturbation in the microbial structure, shifting from a state dominated by commensal organisms to one enriched with pathobionts that promote and progression. This imbalance disrupts the ecological equilibrium maintained by commensals, which typically comprise the majority of the in healthy individuals, limiting overgrowth through and immune modulation. In diseased states, such as periodontitis, often decreases significantly, reflecting a loss of microbial richness and evenness that compromises resilience. Such dysbiotic changes not only drive local oral but also contribute to systemic risks through chronic , bacterial translocation, and release of pro-inflammatory mediators into the circulation. Key biomarkers of oral include elevated abundance of Fusobacterium nucleatum in supragingival and subgingival plaque, a pathobiont frequently associated with inflammatory conditions. Metagenomic analyses using 16S rRNA sequencing consistently reveal genus-level compositional changes, such as increased prevalence of Synergistetes, which correlate with dysbiotic shifts in periodontal pockets. These alterations, detectable through high-throughput sequencing, provide diagnostic insights into the transition from health to , emphasizing the role of community-wide imbalances over isolated pathogen presence and their potential to initiate systemic inflammatory responses. The oral can influence systemic through mechanisms such as bacterial translocation from the oral cavity into the bloodstream and the induction of chronic low-grade inflammation, potentially contributing to extraoral diseases. Periodontal pathogens, including those from dysbiotic biofilms, may disseminate via bacteremia or microaspiration, triggering immune responses that exacerbate distant pathologies. In cardiovascular disease, Porphyromonas gingivalis bacteremia has been shown to promote atherosclerosis by inducing inflammatory lesions in aortic and coronary tissues, as demonstrated in normocholesterolemic animal models where recurrent exposure led to plaque-like formations. Additionally, lipopolysaccharide (LPS) derived from P. gingivalis triggers endothelial dysfunction by exacerbating oxidative stress and inflammatory cytokine release, such as TNF-α, which impairs vascular integrity and accelerates atherogenesis. These effects highlight how oral pathogens contribute to systemic vascular inflammation beyond localized periodontal damage. The relationship between oral and mellitus (T2DM) is bidirectional, with fostering shifts in the oral that worsen glycemic control, while dysbiosis amplifies through inflammatory pathways. Recent analyses indicate elevated levels of in the of individuals with T2DM, particularly under hyperglycemic conditions, correlating with increased periodontal and potential systemic metabolic disruption. This interplay underscores the role of oral microbes in perpetuating a cycle of metabolic and inflammatory dysregulation. Oral microbiome alterations have been linked to cancer progression and early detection. Distinct salivary microbiome signatures, including increased abundance of Leptotrichia species, can predict with high specificity, enabling non-invasive screening by distinguishing affected patients from healthy controls. In oral squamous cell carcinoma (OSCC), Fusobacterium nucleatum promotes tumor invasion by suppressing E-cadherin expression through the Wnt/β-catenin pathway, downregulating this key epithelial adhesion molecule and facilitating epithelial-mesenchymal transition. These microbial interactions may drive oncogenic processes via sustained and altered cellular signaling. Oral has also been implicated in autoimmune diseases such as (RA), where periodontal pathogens like P. gingivalis contribute to disease onset and progression by promoting protein , leading to production (e.g., anti-citrullinated protein antibodies) and joint inflammation. Studies show that individuals with RA exhibit distinct oral microbiome perturbations, including reduced diversity and enrichment of nitrate-reducing bacteria, which exacerbate systemic . Similarly, alterations in the oral are associated with neurodegenerative diseases like (AD). Periodontal pathogens such as P. gingivalis and F. nucleatum have been detected in brain tissues of AD patients, potentially contributing to , amyloid plaque formation, and cognitive decline through mechanisms like gingipain-mediated tau hyperphosphorylation. As of 2025, epidemiological data link poor oral health and to increased AD risk, highlighting the oral-brain axis in neurodegeneration. Respiratory conditions, particularly (VAP), are impacted by aspiration of oral pathogens from dysbiotic into the lower airways, increasing infection risk in vulnerable patients. Oral bacteria such as P. gingivalis and streptococci, shed during , colonize the lungs and provoke , with studies showing direct correlations between oral composition and tracheal aspirate pathogens. This pathway emphasizes the importance of in preventing systemic respiratory complications.

Evolutionary Perspectives

Ancient Origins

The oral microbiota of modern exhibits significant overlap with that of nonhuman , particularly chimpanzees, reflecting shared evolutionary ancestry. Studies of dental from wild chimpanzees reveal a core microbial community including , with relative abundances and site-specific tropisms showing similarity to human oral biofilms, stemming from common ancestries, where arboreal lifestyles and herbivore-like diets rich in fibrous plants promoted the proliferation of Firmicutes phyla, such as species adapted to plant-derived substrates. These microbial patterns underscore a conserved in oral environments prior to hominin divergence. The divergence of hominins from other around 7 to 5 million years ago (mya) marked a pivotal shift in oral composition, driven by dietary transitions toward omnivory. As early hominins like adapted to mixed diets incorporating tubers, seeds, and occasional meat, there were shifts in microbial communities, with higher (Firmicutes) in compared to higher anaerobes like (Bacteroidetes) in chimpanzees. evidence from dental remains, including plaque-like deposits analyzed for microfossils, indicates consumption of starchy , supporting adaptations in host and microbial communities for to extract energy from novel food sources. This dietary flexibility likely selected for more diverse oral taxa, laying the foundation for the modern human microbiome's metabolic versatility. However, reconstructing ancient oral microbiomes faces challenges such as DNA degradation and potential contamination in paleomicrobiological analyses. Pre-Mesolithic populations provide direct archaeological windows into ancient oral ecosystems through analysis of dental , which preserves over 100 distinct microbial taxa, far exceeding the diversity in many modern isolates. Metagenomic sequencing of from individuals reveals a rich tapestry of , including rare such as Methanobrevibacter species, which are underrepresented or absent in contemporary oral microbiomes due to lifestyle changes. These ancient communities, dominated by Firmicutes and Actinobacteria, reflect adaptations to foraged diets high in uncultivated plants and game, with functional genes for degradation indicating robust co-occurrence networks predating agricultural influences. Co-evolutionary dynamics between host and are exemplified by adaptations in genes like AMY1, which encodes salivary alpha-amylase for starch hydrolysis. In early hominins, increased AMY1 copy numbers likely complemented bacterial amylase production in oral biofilms, enhancing overall starch digestion efficiency as diets incorporated more tubers and grains. This gene-microbe interplay, evidenced by parallel expansions in AMY1 across starch-consuming mammals, facilitated mutualistic relationships where host enzymes reduced substrate competition, allowing microbial communities to thrive on partially predigested carbohydrates. Such adaptations highlight the ancient tuning of oral ecosystems to host nutritional needs.

Historical Shifts

The Neolithic Revolution, beginning around 10,000 BCE, introduced agriculture and starchy crops like grains, fundamentally altering human diets and the oral microbiota. This shift favored the proliferation of cariogenic bacteria, as evidenced by ancient dental calculus, which preserves microbial DNA and shows increased abundance of disease-associated taxa such as Veillonellaceae and Porphyromonas gingivalis compared to pre-agricultural hunter-gatherer samples. Caries prevalence rose dramatically, with anthropological analyses indicating a five-fold increase in frequency during this period, attributed to the fermentation of starches by oral bacteria producing acids that demineralize teeth. From the medieval period (500–1500 CE), oral microbial communities exhibited relative stability, reflecting balanced diets with diverse plant and animal sources that sustained higher bacterial diversity similar to levels. Dental calculus metagenomes from European skeletons confirm this continuity, with no major compositional changes until disruptions like the in the 14th century. The plague prompted socioeconomic upheavals and dietary adaptations toward calorie-dense, carbohydrate-rich foods, leading to a decline in methanogenic like Methanobrevibacter and a rise in opportunistic streptococci, which are associated with periodontal pathogens in modern populations. The (18th–19th centuries) exacerbated through the mass production of refined sugars and processed foods, promoting acidogenic bacteria at the expense of microbial balance. Metagenomic analysis of pre- and post-industrial dental calculus reveals a substantial increase in abundance, including a marked rise in from near absence to dominance, alongside reduced overall diversity (p < 0.001). This surge, linked to higher caries rates, reflects the era's dietary shift toward fermentable carbohydrates, with fossil microbiomes indicating up to a 30% relative increase in cariogenic taxa in urbanizing populations. In the 20th and 21st centuries, and enhanced practices have profoundly diminished oral microbial diversity, disrupting symbiotic communities and favoring resistant strains. Longitudinal studies show that antibiotic exposure reduces bacterial richness by 20–30% in the oral cavity, while rigorous eliminates beneficial anaerobes, contributing to observed in industrialized societies.

Current Research and Future Directions

Methodological Advances

Recent methodological advances in oral microbiology have revolutionized the study of the oral microbiota by enabling high-resolution taxonomic profiling, spatial visualization, and simulation of host-microbe dynamics. These innovations, including next-generation sequencing, advanced imaging, and sophisticated systems, have overcome limitations of traditional culture-based approaches, allowing researchers to capture the complexity of polymicrobial communities in health and disease. Integration of computational tools further enhances analysis of large-scale datasets, providing insights into microbial diversity and interactions. Metagenomic techniques have become cornerstone methods for characterizing the oral microbiome's taxonomic and functional composition. 16S rRNA gene sequencing, particularly targeting hypervariable regions such as V1-V3, offers robust taxonomic resolution for oral bacteria by amplifying conserved ribosomal genes while distinguishing species-level variations prevalent in the oral cavity. This approach has identified over 700 bacterial taxa in samples, highlighting the dominance of Firmicutes and Bacteroidetes in healthy oral environments. Complementing this, shotgun metagenomics provides unbiased, whole-genome coverage, revealing functional genes and previously undetected elements like the oral virome. A 2025 metagenomic catalog of the oral virome uncovered extensive viral diversity, including "" sequences from novel bacteriophages associated with periodontal pathogens such as , expanding understanding of viral-bacterial synergies. Imaging technologies enable detailed spatial mapping of oral biofilms, elucidating microbial architecture and interactions within three-dimensional structures. Confocal laser scanning microscopy facilitates non-destructive 3D reconstruction of biofilms, revealing layered distributions where early colonizers like Streptococcus spp. form basal matrices supporting later pathogens. This technique, often combined with vital staining, quantifies biofilm thickness and viability, showing healthy oral biofilms averaging 50-100 μm in depth. Fluorescence in situ hybridization (FISH) complements confocal imaging by using rRNA-targeted probes to visualize specific taxa in situ, allowing simultaneous detection of up to 10 microbial species within intact subgingival plaques and demonstrating co-localization of anaerobes like Fusobacterium nucleatum with inflammatory sites. In vitro models simulate the oral environment to study dynamic host-microbe interactions under controlled conditions. Saliva-coated flow cells mimic salivary flow and shear forces, promoting adhesion and maturation of multispecies biofilms that recapitulate succession patterns, with Streptococcus oralis initiating pellicle formation followed by anaerobic enrichment over 48-72 hours. These systems maintain microbial stability for up to 14 days, enabling longitudinal observation of community shifts. Organoid-based co-cultures advance this by integrating patient-derived oral epithelial organoids with , fostering reciprocal signaling that replicates host immune responses; for instance, exposure to periodontal consortia induces profiles akin to . Such models sustain interactions for seven days, highlighting epithelial barrier modulation by keystone pathogens. Big data integration leverages to analyze population-level oral datasets, uncovering patterns in diversity and health associations. applied to NHANES surveys processes 16S rRNA data from thousands of participants, revealing that healthy oral microbiomes exhibit Shannon indices exceeding 4, indicative of balanced alpha-diversity dominated by commensals. These AI-driven analyses correlate reduced diversity with systemic conditions like , using predictive models to stratify risk based on taxa abundance. Diversity metrics such as Shannon , briefly, quantify evenness and richness to benchmark healthy versus dysbiotic states.

Therapeutic Developments

Therapeutic developments in oral microbiology focus on targeted interventions to restore microbial balance and combat pathogens associated with caries and periodontitis. , particularly strains of Lactobacillus reuteri, have shown promise in reducing cariogenic bacteria such as . Clinical studies demonstrate that daily ingestion of L. reuteri ATCC 55730 via lozenges or fermented milk significantly lowers salivary levels of mutans streptococci, with reductions observed up to 80% in short-term interventions, though sustained effects vary by dosage and duration. For periodontitis, are emerging as adjuncts to non-surgical treatments; a 2025 in diabetic periodontitis patients using alongside showed no additional oral clinical benefits but significant reductions in HbA1c levels (0.6% vs. 0.1% in ), suggesting potential systemic metabolic improvements. Photodynamic therapy (PDT) represents a non-invasive antimicrobial approach, utilizing photosensitizers like methylene blue activated by laser light to disrupt oral biofilms. In vitro studies show that methylene blue-mediated PDT with diode lasers achieves high bactericidal efficacy against Porphyromonas gingivalis, a key periodontal pathogen, with kill rates exceeding 90% through reactive oxygen species generation that targets biofilm-embedded cells. Clinical applications in chronic periodontitis demonstrate reduced microbial loads and enhanced tissue healing when PDT is combined with mechanical debridement, minimizing resistance development compared to traditional antibiotics. Vaccine candidates targeting oral pathogens aim to elicit protective immunity against caries and periodontitis. For S. mutans, surface protein antigens such as I/II (AgI/II) have advanced to phase II clinical trials, inducing salivary IgA antibodies that inhibit bacterial and in subjects. Similarly, anti-gingipain antibodies directed at P. gingivalis proteases (RgpA and Kgp) have demonstrated neutralizing IgG1 responses in preclinical models, preventing alveolar bone loss in experimental periodontitis by blocking factors essential for tissue . Microbiome modulation strategies extend to advanced biologics, including and engineered commensals, to selectively target while preserving beneficial . Bacteriophages specific to S. mutans, such as SMHBZ8, effectively lyse caries-causing strains and inhibit development in models when applied topically, offering a precision alternative to broad-spectrum agents. Engineered commensal , inspired by fecal transplantation principles but adapted for the oral niche, incorporate synthetic gene circuits to produce or modulate ; preclinical designs using plasmid-modified oral streptococci have shown potential in restoring eubiosis and reducing dominance in dysbiotic biofilms.

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