on bacteria, on teeth

Link post

You may have heard that tooth decay is caused by bacteria producing lactic acid. Let’s consider that a little more deeply.

criteria for decay

To effectively cause cavities, bacteria must meet 4 criteria:

Anchoring (with special proteins) to either the tooth surface or something connected to it.
Biofilm production to trap nutrients and protect the bacteria.
Metabolism that produces acid, especially lactic acid.
Growth in acidic conditions.

Some of those can be done by different bacteria, but cavities are made most effectively when a single species can do all of them.

many species of bacteria exist

Converting glucose to lactic acid is one of the (biologically) easiest ways to get energy (ATP) from it. As such, lactic acid bacteria are one of the most common types, and as you may know, there are a lot of bacteria species, maybe around a million. Human mouths have over 700 known bacterial species, and probably more unknown ones.

That being the case, you should expect that multiple types of bacteria are responsible for dental caries, aka cavities.

Streptococcus mutans

If you’ve looked into tooth decay, perhaps you’ve heard of S mutans, which notably meets all of the above criteria. Here’s an introductory paper on it.

If you have a sugary drink, then notice your teeth became more sticky, that’s not the sugar just naturally sticking to your teeth. S mutans makes an enzyme (dextransucrase) that makes a sticky polymer (dextran) from sucrose specifically; using sucrose is more thermodynamically favorable than using glucose or fructose. But of course, there are other bacteria that make exopolysaccharides.

S mutans also:

Produces lactic acid.
Can tolerate relatively low pH.
Uses sortase enzymes to anchor cell wall proteins to teeth.

looking under the lamppost

I’ve heard people say that “S mutans is the bacteria responsible for tooth decay”, and I was immediately suspicious. Sure, it’s been found on teeth, and it can degrade enamel, but outside of a lab, there are always multiple bacteria.

S mutans grows better in lab cultures than most bacteria, which is part of why it’s been focused on. Why is that?

S mutans makes mutacins, which are a type of antibiotic. (The ones produced are strain-specific.) Because of that, at high densities and without something to wash away extracellular chemicals, S mutans tends to outcompete other bacteria present in mouths. As a result, when people tried to culture bacteria from dental plaque, it would often dominate.

If you do PCR on samples of plaque and saliva, you’ll find S mutans in the majority of them, but not all of them.

That said, while there are other cavity-causing bacteria, anything meeting the above 4 criteria and generally adapted to life in mouths will tend to have most of the properties that all S mutans strains do. So, using it as a reference target isn’t wrong.

some other bacteria

First off, there are many strains of S mutans, and the difference between strains and species is a bit loose when there’s asexual reproduction. S sobrinus is closely related to S mutans, meets those 4 criteria, and is associated with cavities, but it’s considered a different species.

Lactobacillus bacteria produce lactic acid and have good acid tolerance. They don’t adhere to teeth as well as S mutans, but can stick to other bacteria that stick to teeth. And Lactobacillus reuteri produces exopolysaccharides.

Actinomyces bacteria seem to be important in cavities, especially on the roots of teeth.

let them fight

Mitis streptococci (eg S sanguinis and S gordonii) release millimolar concentrations of H2O2, which inhibits S. mutans. As mentioned above, S mutans produces mutacins, and some of those target mitis streptococci. Also, S mutans can tolerate lower pH (greater acidity) than mitis bacteria.

Yes, S gordonii can cause cavities, but as it stops growing at higher pH, it does that less than S mutans.

S oligofermentans is also common in humans, and also seems to inhibit growth of S mutans (and other acid-tolerant bacteria) largely via H2O2 production. It’s even been proposed as a probiotic.

treatments

What might be good ways to prevent tooth decay?

chemicals

hydrogen peroxide

As I mentioned above, there’s a tradeoff between acid tolerance and H2O2 tolerance, and different bacteria optimize for different conditions.

Perhaps by adding some H2O2 occasionally, the balance of bacteria could be persistently shifted away from more acid-tolerant species? I’m not sure, but it seems possible, and swishing with 0.1% H2O2 solution seems unlikely to cause much harm. I’m not the FDA, so that’s good enough for me!

chlorhexidine

Lots of mouthwash formulations have chlorhexidine as an antimicrobial. I don’t use those myself, so I hadn’t really looked into it, but let’s see...oh, no, I don’t like the look of that molecule.

And in practice, it...thaaaat’s not a good sign.

Why would you even use chloroaniline...wait, it’s just a mediocre cationic surfactant? Just use a choline fatty acid ester then! What’s wrong with these people?

anti-biofilm drugs

Biofilm production from sugars and anchoring to the tooth surface both involve a small number of enzymes that are outside bacteria. That makes them easier to target with drugs than usual.

There are some people working on fancy anti-biofilm drugs. That seems fine, but also probably expensive. Well, I suppose rich people like having nice teeth?

enzymes

If dextran can be made by enzymes, perhaps people have found enzymes that can unmake it? Indeed, many dextranases have been found.

In that case, perhaps people have considered using those to prevent tooth decay? Well, not only has it been considered, but they’re used in some products for pets! For example, Zymox makes a multi-enzyme product for dogs & cats with: dextranase + mutanase + lactoperoxidase + lysozyme + lactoferrin. You can even buy it on Amazon! (I also have a page just for stuff on amazon, if you need to reach their free shipping threshold.)

(To be precise, lactoferrin isn’t an enzyme; it’s a multipurpose protein that, here, I think mainly acts by chelating iron, which all cells need.)

In theory, the same approach could be used for people, but I would of course never advocate using veterinary products on humans, even if they’re theoretically the same chemicals with the same quality control. Yes, I know the lower costs of veterinary treatment can make US healthcare seem expensive, but don’t worry: private equity groups are working on establishing vet monopolies.

dentin substitutes

Teeth are normally close to an equilibrium where the rate of deposition on them is similar to the rate of dissolution and wear. When deposition is too slow, sometimes people just need more calcium, but when that’s not enough, how about adding some kind of protein that’s similar to dentin and is compatible with normal tooth structure?

That’s right, I’m talking about oligopeptide P11-4. IIRC, it was approved in Europe in 2012 and then one of the Curodont products got FDA approval in 2019. Maybe dentists should use that type of thing more...?

probiotics

There’s a startup called Lantern Bioworks working on a probiotic they call Lumina. That’s a modified strain of S mutans that:

produces ethanol instead of lactic acid
produces an antibiotic
has resistance to that antibiotic
lacks a mechanism for horizontal gene transfer

So, first off, that antibiotic is already produced by some S mutans strains, and it hasn’t led to their dominance. It seems relatively easy for bacteria to develop resistance to, so they would. Or rather, some already have, since it exists in nature.

And I think horizontal gene transfer would still happen despite the attempt at preventing it. Also it...already happened.

Also, if you change S mutans to not produce lactic acid, that strain will get outcompeted by bacteria that can’t tolerate pH as low but produce, say, some H2O2. As mentioned above.

Also, if you have some GM strain of S mutans that anchors to teeth and kills off other strains but doesn’t produce lactic acid, then Lactobacillus will stick to your GM bacteria and proceed to produce lactic acid.

So there are some problems. But is it possible to produce a GM bacteria that would displace S mutans and related species like S sobrinus? It’s a tricky problem, and my biochemistry skills are meager compared to my teachers, but I’m inclined to say “yes”.

How might you do that? I’d probably start with one of those naturally competitive bacteria that are less acid-tolerant and make some H2O2. Actually, maybe I’d start by looking at bacteria in the mouths of people with no cavities, like this. See also eg L paracasei 28.4. Folks like Lantern Bioworks should remember to bow to the master before they begin.

brush your teeth

Many people around the world use brushes to clean their teeth. You may even have done that yourself. Often, a paste is added to the brush used to clean teeth—“toothpaste” and a “toothbrush”, if you will.

That brushing can break up biofilms, and remove bacteria and food from teeth. In theory, it could be done many times a day, but there are a few problems with that:

It takes some time.
Most people don’t carry a toothbrush & toothpaste with them, and using it in eg a restaurant bathroom tends to be inconvenient.
Toothpaste is kind of abrasive, and using it several times a day can be worse than having some more bacteria.

There’s actually a partial solution to those problems: additional tooth brushing without using toothpaste. Most people think you have to use toothpaste every time you brush your teeth, but that’s a big lie told by Big Toothpaste.

eat less sucrose?

I suppose that’s an option, but if the replacement is high-fructose corn syrup, is that an improvement? From a shallow perspective they seem metabolically equivalent, but there actually are some differences in the effects. Longer-term, fructose is more reactive, so high blood levels of fructose instead of sucrose seems somewhat worse.

From my perspective, trading some of the problems of high blood sugar for more-easily-mitigated dental issues seems like a sweet deal.