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While it is not exactly pleasant to imagine the mouth as an ecosystem teeming with microbial life, that is exactly what it is. The mouth, or oral cavity in scientific terms, hosts many kinds of bacteria, fungi, archaea and viruses that make their homes in saliva and on teeth in the form of biofilms known as .

Tooth decay, or caries, happens when bacteria in the mouth break down sugars and produce acids that eat away at the hard, mineral substance known as enamel, which protects teeth from physical, thermal and chemical stresses. Enamel remineralizes naturally as minerals are deposited on teeth through saliva, certain foods and dental products, like toothpaste, but if erosive stresses outpace the remineralization process, caries can begin to develop. In the long term, this can lead to pain or sensitivity, as well as visible dark spots on the teeth. Caries is estimated to affect up to making it the  in the world.

What Causes Caries?

For a long time, a ‘1 disease, 1 pathogen’ paradigm dominated scientists’ understanding of dental caries, with the bacterium Streptococcus mutans as the central culprit. S. mutans is a common inhabitant of the human oral cavity. It was thought to be public enemy number 1 when it comes to caries because its presence was  incidence of caries. This paradigm even led to suggestions to  against dental caries by specifically targeting S. mutans.

In the last decades, scientists have come to understand that S. mutans is actually only a part of the puzzle—the composition of bacterial biofilms in the mouth and on teeth , and not everyone with caries has an abundance of S. mutans. Caries is now considered a non-communicable disease, meaning it is not caused by an infectious agent, but rather develops based on factors including genetics, behavior and the composition of the oral microbiota. In general, an increase in bacteria that produce acid, or can tolerate acidic conditions, can . This mirrors the concept of dysbiosis in gut health, which describes an imbalance in bacterial composition of the gut—lower overall diversity, with a reduction in beneficial microbes and increase in potentially harmful ones—that is linked to non-communicable diseases such as irritable bowel syndrome.

Studying the Oral Microbiota

Although the mouth and teeth are more accessible than the gut, and therefore technically easier to sample directly, it is still difficult to perform controlled experiments to ascertain cause-and-effect in the oral microbiome. This makes it challenging to discover the molecular mechanisms driving caries development, or to develop new interventions for caries that target the oral microbiota.

One way that scientists can learn about the oral microbiota and study the mechanisms driving caries formation is by taking saliva or dental plaque samples from patients and studying them in the lab. In one study, researchers used microscopy to  from caries-free or caries-afflicted children. They saw that caries-afflicted saliva had clumps of intermixed bacteria and fungi, while caries-free saliva had mostly single bacterial cells or bacteria-only clumps. Looking closer, scientists found that the bacteria-fungi clumps mainly consisted of S. mutans and the yeast Candida albicans.

Armed with this information, the researchers re-created the bacteria-fungus clumps in the lab to study how they form and function. They found that the fungus holds on to bacteria, which get entangled in fungal hyphae and stuck on molecules called alpha-glycans. They also looked at how the bacteria-fungus clumps attach to enamel-like surfaces and found something astonishing—the clumps can migrate. The growing fungal hyphae effectively ‘walk’ bacterial clumps along surfaces as the clumps are carried along by the expanding hyphal structures. This finding has implications for caries development, especially as co-aggregation appeared to enhance enamel decay, compared to either the bacteria or fungus alone.

Building a Mini-Mouth for the Lab

In addition to taking plaque and saliva samples, scientists may use laboratory models to study the microbial ecology of the mouth in a more controlled environment.

One such model, first developed by scientists in the 1990s, consists of a  that broadly represent the main players found in the mouth. The community grows in a chemostat, a type of bioreactor where parameters like nutrient input and pH can be controlled to keep the bacteria inside growing in a ‘steady state.’ This chemostat community has been used to study the microbial ecology behind oral health and disease in different contexts. For example, by performing experiments with the chemostat community, researchers showed that S. mutans is  that benefits from acidic conditions, suggesting that it may not be the only caries-causing microorganism in the mouth. This study was published in 1998, before it was widely known or accepted that S. mutans is not the lone harbinger of caries.

The oral chemostat community has also been used to explore exactly how oral health interventions work. One such intervention is , a common ingredient in toothpaste and mouthwash. Fluoride is known to reduce tooth decay by helping tooth enamel remineralize after normal exposure to acids from food, drink and the stomach, which initiate erosion. However, whether fluoride also has antimicrobial effects was unclear until the early 2000s, when scientists pulsed the oral chemostat community with glucose with or without a low concentration of fluoride and assessed pH and community composition after 10 days. Without fluoride, S. mutans and Veillonella dispar, another bacterial species that has been associated with caries and is known to  of other pathogenic species by detoxifying its surroundings and providing iron to its neighbors, became highly abundant. At the same time, many other acid-sensitive community members withered due to the low pH.

When fluoride was added, however, the pH remained closer to normal levels, and acid-sensitive community members could survive. S. mutans remained at a low abundance in the community, likely because its competitors were not suppressed and could keep S. mutans in check. Surprisingly, the abundance of V. dispar was also high, but the fluoride community was still more diverse compared to the no-fluoride community, where S. mutans and V. dispar dominated. The researchers concluded that even low concentrations of fluoride could suppress caries-causing bacteria by stopping pH drops that give them an advantage against acid-sensitive bacteria, thus helping to maintain a normal oral microbiota.

Another oral health intervention that the chemostat community has been used to explore is xylitol, a sugar alcohol first discovered in beechwood and a common sweetener in sugar-free chewing gums and mints. Xylitol is a non-cariogenic sugar, meaning that it does not promote caries development, unlike sugars such as sucrose (table sugar) and fructose (fruit sugar). Researchers in Finland, one of the world’s major xylitol-producing countries first discovered that xylitol consumption was  in the 1970s. Two decades later, the oral chemostat community was used to explain the mechanism behind these observations. When the researchers exposed the community to  alongside glucose, they found that the rate of acid production was decreased compared to when only glucose was pulsed in. The mechanism was similar to that of fluoride; with xylitol, the stable pH prevented S. mutans from taking over, allowing the community to maintain its normal composition.

Probiotics for the Mouth?

In addition to interventions such as fluoride and xylitol, probiotics are also used for managing and treating non-communicable diseases caused by microbial community dysbiosis. Probiotics work by introducing 1 or more beneficial microbial species to bring the community back to a healthy state, and research to examine the effectiveness of probiotic interventions for managing caries is ongoing. For example, there is some evidence that probiotic bacteria,  and  can inhibit the growth of caries-causing bacteria in dental plaque. This inhibition can occur through competition for shared resources, as well as the  by the probiotic strains.

However, the oral probiotics market is a complex landscape; many products marketed as probiotics against oral health issues contain bacteria that have been deemed safe to use in such products, but the benefits discovered by scientists are highly specific to certain strains. That means that not all lactic acid bacteria are equally beneficial against caries—in fact, some strains might even . Thus, not all oral probiotics can . This makes it difficult for both clinicians and consumers to make informed decisions that actually help to prevent or manage caries.

Researchers are always learning more about how caries develop, and what can be done to prevent them. The WHO has set a goal to reduce the incidence of oral disease, including caries, by . However, challenges remain, as the global incidence of oral disease  in the past 30 years, suggesting that current interventions are not enough. The only region in the world where caries incidence has decreased is Europe, indicating that other regions, particularly those that are resource-limited, need more attention. As it stands, the best we can do is follow our dentist’s tried-and-true advice—brush well, avoid large amounts of sweets and remember to floss!
 

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Microbial communities thrive in every environment, from our bodies to the atmosphere, making the microbiome central to the health of people, ecosystems and the planet.