Xylitol and its role in cariogenic onset

Author: Dario Catozzi
Date: 18/03/2013


A brief research about cariogenesis and possible positive effects of xylitol use in diet.

1. Oral environment

The human oral cavity is also called the human oral microbiome. This is because the human oral cavity can contain several environments, as gingival epithelium and tooth surface: the last one is the only exposed place of the human body that does not have a regulated system of shedding surfaces.
This allows a numerous amount of microorganisms to adhere to the surface of tooth, giving birth to the dental plaque.
The mouth harbors a various and complex microbial community, and bacteria colonize mouth since the first days (or hours!) of life, occupying the ecological niches provided by gingival epithelium at first, and then by tooth surface.

Dental plaque is a perfect example of biofilm: a microbial community adhering to a surface, with a definite and specific organization.
Here, the plaque genesis starts with the adhesion of salivary glycoproteins on the enamel. Now, some bacteria may be caught because of Wan Der Walls forces between their transmembrane proteins and tooth glycoproteins.

The last step is the so called “co-adhesion”, in which is the inter-gender aggregation of different bacteria: a synergy of different microorganisms is created, including an alimentary one (due to enzymatic complementation, to digest macromolecules using an enlarged enzymatic set) dental plaque a completely self-sufficient ecosystem.1
Human cavity is consider a microaerobic-anaerobic environment, so the most of our bacteria tolerate a low concentration of O2, but the main way for ATP production is fermentation (anaerobic respiration).
It has been estimated that 25,000 species of bacteria reside in the mouth. Studies have found that out of the 25,000 species that exist in the oral cavity, but the most of them places at the mucosa (epithelial cells), and just about 1,000 species can exist as part of the dental biofilm ecosystem.

1 Principi di Microbiologia Medica, Antonelli et al. Casa Editrice Ambrosiana 2012, Milano

2. Cariogenesis

Dental caries, also known as tooth decay or a cavity, is an infection that causes demineralization and destruction of the hard tissues (enamel, then dentin and cementum) of the tooth, usually by production of acid by bacterial fermentation of the food eaten by the host.
The most frequently responsible bacteria for dental cavities is Streptococcus mutans, followed by other streptococci, as Streptococcus sobrinus, and lactobacilli. [2] Their peculiar trait is to grow better on weakly acid medium.

If left untreated, the disease can lead to pain, tooth loss and infection. Today, caries remain one of the most common diseases throughout the world.
Tooth decay disease is caused by specific types of bacteria that produce acid in the presence of fermentable carbohydrates such as sucrose, fructose, and glucose. The mineral content of teeth is sensitive to increases in acidity from the production of lactic acid (lactic fermentation is the most common).

The pH level of oral cavity is almost neutral, [1] but after a meal, fermentation starts and the pH at the surface of the tooth drops. Below 5.7 ( critical level ), demineralization proceeds faster than remineralization (meaning that there is a net loss of mineral structure on the tooth's surface). In addition, bacteria’s sensibility to pH level is various: the most of them does not tolerate a low pH for a long time, but some streptococci as S. mutans (and some others genders) do. This leads to natural selection of cariogenic bacteria in case of frequent carbohydrates introductions (for example candies).

Shortly, the cariogenic process breaks the balance among the different members of the dental plaque.

2 Role of Streptococcus mutans in human dental decay, 1986

3. Pathogenic determinants of cariogenic bacteria

  • Internalization of carbohydrates: there are mainly 3 transport systems, but just a few bacteria own all of them.
    1. Phosphoenolpyruvate-tranferase system : a really efficient system that allows internalization and contemporary phosphorylation of carbs. It’s constitutively expressed for glucose, mannose, sucrose, and inducible for lactose (by the famous LAC-operon), mannitol, sorbitol.
      It loses efficiency with high levels of sugars and with low pH.
    2. ATP-dependent permease: internalization and phosphorylation on the inner side of the plasmatic membrane. Fully efficient with high levels of substrate and low pH. Expressed in just few cariogenic species, for example S.mutans.
    3. Other multiple transport system, with variability within genders.
  • Fast metabolism and proliferation: the proliferation speed is directly proportional to the conversion capability of carbohydrates into energy. Bacteria with faster metabolism are evolutionarily advantaged over the other members of the dental plaque.
  • Environmental modifications: the presence of bacterial species with some of the previous skills lead to environmental modifications.
    For example, after a meal oral pH drops, and the usual transport-proteins lose efficiency. S.mutans, with an ATP-dependent permease can internalize a greater amount of glucose and other carbohydrates then the surrounding microbes (increased competitiveness), and manages to “feed” its fast metabolism. Proliferation will provide an increased number of S.mutans in the plaque, and the increased amount of S.mutans causes the establishment of a sort of loop: they will turn the pH lower and lower, up to the critical level of 5.7, when demineralization will start.
    Another bacterial gender, Lactobacillus, is identified as a “second line” cariogenic, because it doesn’t make the pH drop, but when it reachs almost 5.5, Lactobacilli are more efficient than in neutral pH and then stabilize the current pH level.

4: XYLITOL, the tooth-friendly sugar

Xylitol , technically a polyalcohol (alditol) [1,2,3,4,5-Pentahydroxypentane] is a nonfermentable3 sugar naturally found in fibers of many fruits and vegetables, first of all corn husks and sugar cane bagasse.
Industrial production starts from xylan (a hemicellulose) extracted from hardwoods or corncobs.

Early studies from Finland in the 1970s found it inhibiting cavity-digging bacteria, simply because they prefer six-carbon sugars or disaccharides, while xylitol is non-fermentable and cannot be used as an energy source, interfering with bacterial growth and reproduction. [4]
Bacteria that takes more disadvantage of this skill are the most competitive ones, that internalize more carbohydrates, and so they fill up with this nonfermentable sugar (using sorbitol transporters mainly).
A damnation if you live in an anaerobic environment!

The harmful micro-organisms are starved in the presence of xylitol, allowing the pH to increase and the mouth to remineralize damaged teeth with less interruption. This same property renders it unsuitable for making bread as it interferes with the ability of yeast to digest sugars.

This doesn’t kill S.mutans, just decrease its proliferation rating and balance it with the one of the other members of the plaque. That’s why xylitol is certified as a “tooth-friendly” product.

3 Acid production from Lycasin, maltitol, sorbitol and xylitol by oral streptococci and lactobacilli, 1979

4 Comparative effects of the substance-sweeteners glucose, sorbitol, sucrose, xylitol and trichlorosucrose on lowering of pH by two oral Streptococcus mutans strains in vitro, 1979

5. Scientific evidence

Several articles display there is a significant reduction of caries and level of S.mutans [5] in the plaque in xylitol-sweetened chewing-gum eaters. However, despite these promising conjectures, a systematic review of clinical trials could not find conclusive evidence that xylitol was indeed superior to other polyols such as sorbitol, another (usually) nonfermentable sugar. This [6] may demonstrate that xylitol has no individual skill, but other reviews seem to demonstrate the opposite. [7]
This may be confusing, but all this difference is supposedly created by some S.mutans strains, actually capable to ferment sorbitol, while others aren't. This makes statistically relevant differences in outcomes, especially in some xylitol-versus-sorbitol studies.

Luckily, benefits from use of xylitol (vs placebo or vs nothing) is evident. [8]

5 Effect of xylitol on dental caries and salivary Streptococcus mutans levels among a group of mother-child pairs, 2011

6 Effect of xylitol versus sorbitol: a quantitative systematic review of clinical trials, 2012

7 The use of sorbitol- and xylitol-sweetened chewing gum in caries control, 2006

8 Six months of high-dose xylitol in high-risk caries subjects-a 2-year randomised, clinical trial, 2012

6. Conclusions

Despite of some contradictions, xylitol is consider helpful in caries prevention, and it’s use is spreading word-wide, starting from Northern Europe (Finland) and United States (with the approval of FDA) [9], with xylitol-sweetened chewing-gums [10], sweeteners, cookies exc..
Today, caries remain one of the most common diseases throughout the world, so encourage the assumption of xylitol-flavored products may be a way to both preserve health and save money.

9 FDA Code of Federal Regulation, 2012

10 Xylitol-based candies and lozenges may reduce caries on permanent teeth, 2012

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