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Most of the data available so far identifies bacterial species that tend to be associated with healthy versus diseased oral cavities but not much is known about exactly what health-associated ones do apart from keeping out the disease-associated ones.

Oral Cavity, A Complex Ecosystem Of Several Specialized Ecological Niches

Gaining insight begins with the appreciation that the oral cavity is a complex habitat further sub-divided into distinct smaller ones ranging from the non-keratinized Oral mucosa to the keratinized Tongue and gingiva, i.e., Gums, as well as Tooth enamel and a variety of dental implants. Thus, depending on its proximity to the gum line, dental plaque is either supra- or subgingival, and the bacteria that inhabit these two regions are different, supragingival plaque dominated by gram-positive Streptococci while subgingival by gram-negative anaerobic bacteria (1).

Since the oral cavity is exposed to the outside world, these surfaces are colonized soon after birth, with some evidence suggesting vertical (mother-to-baby) transmission (2) as well as similarities between family members (3). Stable inhabitants, formally called autochthonous, establish Biofilm, a kind of super-organism consisting of cooperating microbes. Being open, oral cavity also gets plenty of visitors, transients, formally called allochthonous.

Older studies suggested oral cavity diseases are associated with changes in microbial diversity (1).

Gum diseases, i.e., Periodontal pathology, and tooth decay, i.e., Dental caries, are associated with increase (4, 5, 6) and decrease (7), respectively, in microbial diversity. More recent state-of-the-art molecular approaches (8, 9) confirm these decades-old findings. This implies oral cavity disease isn’t so much a matter of presence or absence of certain microbes since those with disease-causing potential, i.e., pathobionts, are present even in health (10) but rather about their relative proportions in complex biofilms.

Colonisation resistance Is A Key Feature Of Healthy Oral Cavity Microbiota

Like other microbe-associated body sites, the oral cavity too is a series of specialized niches occupied by specific microbes capable of specialized functions both necessary and predicated on some inherent properties of these niches. The ones who establish stable presence in the form of complex, multi-species biofilms dominate their specific niches by preventing others, including pathogens, from establishing themselves, i.e., Colonization Resistance (11). When the oral cavity is stably colonized by beneficial microbe biofilms, it’s healthy. Instability in beneficial microbe colonization is a weakness that’s then exploited by more harmful and even pathogenic species to dominate oral cavity biofilms, with the outcome either tooth decay (Dental Caries) or gum disease (Periodontitis).

Tooth decay (Dental caries) is associated with certain species of Streptococci such as Streptococcus mutans and species of Lactobacilli (12) while subgingival anaerobes establish their communities within periodontal pockets, some of whom such as Porphyromonas gingivalis are associated with gum disease (Periodontitis) (13, 14).

Obviously diet profoundly influences not only which bacterial species stably establish within oral biofilms but also dominate.

  • Thus though S. mutans is part of normal oral microbiota (15), it doesn’t dominate in healthy oral cavities.
  • However, its capacity to metabolize sucrose more efficiently compared to other oral bacteria (16) gives it a competitive advantage in the oral cavities of those who predominantly consume the highly processed, sucrose-heavy ‘Western’ diet.
  • S. mutans can also convert sucrose to adherent glucans, which helps it to attach more strongly to teeth (17).
  • S. mutans also rapidly converts sucrose to lactic acid, giving it an added selective advantage owing to its intrinsic capacity to withstand such acidic environments (18, 19).
  • These properties may help S. mutans and Lactobacilli dominate in tooth decay, i.e., dental caries, the latter because they metabolize lactic acid generated by S.mutans.

Similar studies done decades apart, scraping plaques from people with or without gum disease and culturing the bacteria that grew out with bacterial species associated with gum disease showed plaques from people without gum disease can inhibit growth of gum disease-associated bacterial species (20, 21). How?

  • Streptococcus sanguinis is considered an inhabitant of normal dental plaque. Less acid-tolerant than its presumed niche competitor, S. mutans, S. sanguinis produces Hydrogen peroxide, toxic for S. mutans, which typically lacks capacity to effectively neutralize it (22, 23). Thus, dental plaques rich in S. sanguinis contain relatively lower proportions of dental caries-associated S. mutans and periodontitis-associated P. gingivalis (20).
  • Veillonella species (24) and S. oligofermentans (25) readily metabolize lactic acid secreted by S. mutans. A revealing window into how inter-species competition can engender colonization resistance, S. oligofermentans not only utilizes S. mutans-generated lactic acid but converts it into hydrogen peroxide, highly toxic to the latter (26).
  • Streptococcus gordonii offers another plausible example of colonization resistance tactic. Another inhabitant of healthy oral cavities, in vitro it could prevent stable S. mutans colonization by inactivating one of its important resistance mechanisms , ability to synthesize a Quorum sensing molecule, CSP (competence-stimulating peptide) (27). When thus hobbled, S. mutans is much less capable of resisting natural salivary antimicrobial peptides such as Histatin (1).
  • Oral cavity bacteria also secrete Bacteriocin. Proteinaceous toxins, bacteriocins differ from antibiotics, having a much narrower killing spectrum and acting on related organisms (1).

Thus, as long as diet is varied enough to also allow stable plaque colonization by base-producing microbes, acid-producing S. mutans wouldn’t be able to predominate and take over local plaque ecosystem.

Food web Relationships Between Normal Oral Cavity Microbes Help Maintain Their Stability

As is the hallmark of ecosystems consisting of mutually dependent residents, the healthy oral cavity too contains microbes engaged in Food web activities, i.e., metabolic end products of one species used by others.

  • Oral biofilm Streptococci synthesize lactate that Veillonella use (1).
  • S. sanguis and S. oralis are inhabitants of healthy oral biofilms. In vitro culture studies suggest their mutually helpful, i.e., synergistic, capacity to digest mucins helps them more efficiently use such complex host sugars as nutrition (28).
  • Oral cavity is constantly bathed in saliva and gingival crevicular fluid. Composite of products of not just human tissue cells but also microbes, some microbial inhabitants appear to engage in synergistic/mutualistic interactions to overcome inherent handicaps to colonize. This seems to be the case with Actinomyces naeslundii and S. oralis that alone colonize saliva-coated surfaces poorly and yet can form extensive biofilms together by presumably combining their metabolic activities (29).

However, food web processes can also help shift oral biofilms to dominance by more pathogenic species. Though inhabitants of normal oral cavity, P. gingivalis, Fusobacterium nucleatum, Treponema denticola and Tannerella forsythia are also implicated in periodontal disease.

  • In vitro culture studies show P. gingivalis can metabolize succinate produced by T. denticola (30) while the latter can use isobutyric acid secreted by the former (31).
  • Both F. nucleatum and T. forsythia seem to secrete factors that stimulate growth of P. gingivalis (1).

Thus, whether mutualistic interactions of beneficial or harmful bacteria dominate in a given oral cavity is outcome of diet, oral hygiene and host genetic polymorphisms.

Why Knowledge Of Bacteria Function In Healthy Oral Cavity Is Better Gleaned From Older, Not Newer, Studies

Since the 2000s an explosion in molecular biological tools, so-called Omics, has led to a similar explosion in human microbiome studies. Since the oral cavity is one of the most easily accessible of all the GI tract niches, human oral cavity microbiome has become the best characterized in terms of the kinds of bacteria present in healthy versus unhealthy mouths.

  • Since such typically technocratically driven processes focus primarily on generating an avalanche of data and explore no underlying hypotheses, one may wonder whether the healthy human oral cavity microbiome’s function is simply absence of disease. That is to say, given the monumental scale of molecular biology data generated on this topic since at least the mid-2000s, it’s shocking how little is known about what any of it even means.
  • With older prejudices implicitly carried forward, there’s also been no attempt so far to synthesize the roles of bacteria and fungi in healthy oral cavities since fungi like Candida albicans were previously assumed to only represent disease states. Their repeated presence in healthy oral cavities suggests this idea needs revising (32).
  • Even less is known about role of Archaea such as Methanobrevibacter species frequently found in healthy oral cavities. Their increasing identification in gum disease (Periodontal pathology) suggests they too may be involved in such disease processes but how? Only in promoting growth of pathogenic bacterial species (33) or as initiators and perpetuators themselves?
  • Meantime overweening allegiance to novel technologies is powering this entire absurd process forward with the implicit hope that Data mining will uncover hidden patterns allowing certain predictive hypotheses to be made.
  • If past is any predictor of future, the failure of past dependence on novel molecular biological approaches alone to yield predictive insight into complex biological phenomena suggests a similar fate awaits the current giddy immersion in the latest molecular biological toys. A useful and telling example from the recent past is Microarray analysis techniques, the focus of tens of thousands of papers since the late 1990s, which nevertheless yielded little or no improved insight into disease processes nor did they much illuminate possible future predictive approaches to better understand them.
  • Necessity of extrapolating data from in vitro culture studies referenced in this answer is their major caveat. Nevertheless, we’d understand oral cavity-bacteria interactions better with more such experiments, especially in vitro co-cultures of human oral epithelial cells with candidate oral cavity commensals, more so co-cultures with commensal biofilms but such experimental approaches are technically much more challenging compared to powering a few cheek swab or saliva samples through the latest molecular biology apparatus. Hence the current absurd status quo.


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